A Phase 2/3 interventional study of Cetuximab and Durvalumab in Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Head and Neck Squamous Cell Carcinoma and Hypopharyngeal Squamous Cell Carcinoma, sponsored by National Cancer Institute (NCI). Completed at 256 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-27.
Sponsored by National Cancer Institute (NCI) · Phase 2/3, Interventional, and Treatment
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Among 28 studies in Oropharyngeal Neoplasms by National Cancer Institute (NCI) — 6 open to participants now, 11 under way, 3 of them phase 3. Oropharyngeal Neoplasms · National Cancer Institute (NCI).
Among the 28 studies in Oropharyngeal Neoplasms by National Cancer Institute (NCI), this one is the 5th largest by enrollment of the 24 interventional ones that give a count, is one of 3 that started in 2018, is one of 3 in phase 2/3, and was the 11th registered.
369 studies on the registry are indexed under Oropharyngeal Neoplasms; 103 are open to participants now.
Browse Oropharyngeal Neoplasms studies →6 of the 28 studies in Oropharyngeal Neoplasms by National Cancer Institute (NCI) are open now, in 2 countries. Recruiting first, the newest first:
National Cancer Institute (NCI) · Sites in United States
Ages 18+
National Cancer Institute (NCI) · Sites in United States
Ages 18+
National Cancer Institute (NCI) · Sites in United States
Ages 18–120
National Cancer Institute (NCI) · Sites in United States
Ages 18+
National Cancer Institute (NCI) · Sites in United States, Canada
Ages 18+
By country, each count listing its studies:
Of the 89 Oropharyngeal Neoplasms studies recruiting now, 76 (85%) set no upper age limit and 5 (6%) stop at 75 or younger; none take children under 18; 7 take healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
28 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 12 · Phase 2 18 · Phase 3 5
First in 1996; this study’s year is marked. 3 started in 2018.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 196 is above the median of 52 across 265 interventional studies indexed under Oropharyngeal Neoplasms.
Median enrollment 49 across the 24 interventional studies, 1,000 across the 1 observational. Of the 13 that completed or were terminated, 10 (77%) have results posted.
This tab as a report to print or save as PDF → With an account.
National Cancer Institute (NCI) is the lead sponsor of 3,556 studies on the registry; 336 are open to participants now.
Of its 412 completed or terminated interventional studies of FDA-regulated products, 374 (91%) have results posted.
2 of the studies in Oropharyngeal Neoplasms by National Cancer Institute (NCI) that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT05136196National Cancer Institute (NCI)BiCaZO: A Study Combining Two Immunotherapies (Cabozantinib and Nivolumab) to Treat Patients With Advanced Melanoma or Squamous Cell Head and Neck Cancer, an immunoMATCH Pilot Study | 2027-01-01 |
| NCT05172245National Cancer Institute (NCI)Testing the Addition of Ipatasertib to Usual Chemotherapy and Radiation for Head and Neck Cancer | 2027-07-01 |
Add all 2 to your calendar (.ics) → With an account.
Among the 28 studies in Oropharyngeal Neoplasms by National Cancer Institute (NCI), from their registry updates:
This tab as a report to print or save as PDF → With an account.
This phase II/III trial studies how well radiation therapy works with durvalumab or cetuximab in treating patients with head and neck cancer that has spread to a local and/or regional area of the body who cannot take cisplatin. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cetuximab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. It is not known if radiation therapy with durvalumab will work better than the usual therapy of radiation therapy with cetuximab in treating patients with head and neck cancer.
PRIMARY OBJECTIVES:
I. To determine the safety of radiotherapy (RT) with concurrent and adjuvant anti-PD-L1 therapy (MEDI4736 [durvalumab]) is safe in patients with locoregionally advanced head and neck cancer (HNC) who have a contraindication to cisplatin. (Lead-in) II. To test the hypothesis that concurrent RT and anti-PD-L1 therapy improves progression free survival (PFS) compared to standard therapy (RT with concurrent cetuximab) in patients with locoregionally advanced HNC who have a contraindication to cisplatin. (Phase II) III. To test the hypothesis that concurrent RT and anti-PD-L1 therapy improves overall survival compared to standard therapy (RT with concurrent cetuximab) in patients with locoregionally advanced HNC who have a contraindication to cisplatin. (Phase III)
SECONDARY OBJECTIVES:
I. To compare toxicity using Common Terminology Criteria for Adverse Events (CTCAE) and Patient Reported Outcomes (PRO)-CTCAE between patients treated with RT + anti-PD-L1 therapy versus RT/cetuximab.
II. To test the effect of anti-PD-L1 therapy in the subpopulation of patients with tumors that overexpress PD-L1.
III. To compare overall survival, response (at 4-month fludeoxyglucose F-18 [FDG]-positron emission tomography [PET]-computed tomography [CT]), locoregional failure, distant metastasis, and competing mortality in the two arms by known risk factors, including p16 status and omega score.
IV. To test the hypothesis that MEDI4736 (durvalumab) therapy arm will have less decline in the physical function domain of European Organization for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30 version 3.0) based on the change in score from baseline to 12 months from end of RT, compared to the cetuximab-RT arm in patients with locoregionally advanced HNC who have a contraindication to cisplatin.
V. To test the hypothesis that MEDI4736 (durvalumab) therapy arm at 1 year (from end of RT) will have less decline in swallowing related quality of life (QOL) using the M. D. Anderson Dysphagia Inventory (MDADI) total composite score, based on the change in score from baseline to 12 months from end of RT, compared to the cetuximab-RT arm in patients who are medically unfit for cisplatin.
VI. To compare swallowing related performance and function short and long term using the Performance Status Scale for Head \& Neck Cancer Patients (PSS-HN).
VII. To evaluate gastrostomy tube retention rates between arms.
EXPLORATORY OBJECTIVES:
I. To test the hypothesis that radiation combined with MEDI4736 (durvalumab) enhances the adaptive immune response using three types of immunophenotyping compared to radiation combined with cetuximab.
II. To compare overall QOL short term (end RT-8 months) and long term (12-24 months from end of RT) between arms using the EORTC QLQ-C30 version 3.0/HN35.
III. To evaluate swallowing related QOL short term (end RT-8 months) and long term (12-24 months from end of RT) using the EORTC Head and Neck (HN)35 swallowing domain and MDADI (subscales) between arms in patients with locoregionally advanced HNC who have a contraindication to cisplatin.
IV. To evaluate patient reported fatigue using the fatigue items in the EORTC QLQ and PRO-CTCAE.
V. To compare clinician and patient reported toxicity using CTCAE and PRO CTCAE.
VI. To explore health utilities between cetuximab and MEDI4736 (durvalumab) RT using the European Quality of Life 5 Dimensional-5 Level (EQ5D-5L).
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive cetuximab intravenously (IV) weekly over 60-120 minutes. Treatment repeats every week for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Beginning 5-7 days after first cetuximab dose, patients undergo intensity modulated radiation therapy (IMRT) 5 fractions per week for up to 7 weeks.
ARM II: Patients receive durvalumab IV over 60 minutes every 4 weeks. Treatment repeats every 4 weeks for up to 7 cycles in the absence of disease progression or unacceptable toxicity. Beginning week 2, patients undergo IMRT 5 fractions per week for up to 7 weeks.
After completion of study treatment, patients are followed up at 1 month, every 4 months for 1 year, every 6 months for 2 years, then annually thereafter.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Patients must have confirmed, previously untreated, unresected squamous cell carcinoma of the larynx, hypopharynx, oropharynx, oral cavity, or carcinoma of unknown head/neck primary prior to step 1 registration; submission of hematoxylin and eosin (H\&E) stained slides and formalin-fixed and paraffin-embedded (FFPE) tissue block (or punch of FFPE block) to the biospecimen bank at University of California, San Francisco (UCSF) for central review for oropharyngeal and unknown primaries and for p16 analysis for all other non-oropharyngeal primaries is mandatory for all patients; investigators should check with their pathology department regarding release of biospecimens before approaching patients about participation in the trial; for oropharyngeal and unknown primaries, submission of H\&E and p16 stained slides (with the required block for ) to the biospecimen bank at UCSF for central review is also required prior to step 2 registration
Patients must have locoregionally advanced head and neck squamous cell carcinoma (HNSCC)
Based on the following minimum diagnostic workup within 60 days prior to step 1 registration:
Patients must have a contraindication to cisplatin as defined in the following bullet points; sites must complete the online tool at comogram.org prior to step 1 registration to determine if the patient is eligible; the scores must be recorded on a case report form (CRF)
Age >= 70 with moderate to severe comorbidity or vulnerability to cisplatin, defined as having one or more of the following conditions within 30 days prior to step 1 registration:
Age \< 70 with severe comorbidity or vulnerability to cisplatin, defined as having two or more of the following conditions within 30 days prior to step 1 registration
Age >= 18 with an absolute or relative contraindication to cisplatin, defined as one or more of the following within 30 days prior to step 1 registration:
History of hearing loss, defined as either:
For women of , a negative serum or urine pregnancy test within 14 days prior to step 1 registration; Note: women will be considered if they have been amenorrheic for 12 months without an alternative medical cause; the following age-specific requirements apply:
For patients with oropharyngeal or unknown primaries: p16 determination by immunohistochemistry (defined as greater than 70% strong nuclear or nuclear and cytoplasmic staining of tumor cells), confirmed by central pathology review
Exclusion Criteria:
Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
If both of the following conditions are present, the patient is ineligible:
p16-positive carcinoma of the oropharynx or unknown primary that are T0-3, N0-1 (AJCC 8th Edition)
Respiratory illness requiring hospitalization at the time of step 1 registration
Active or prior documented or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.)
The following are exceptions to this criterion:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
PD-1, PD-L1 and checkpoint inhibitors
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CD4 count
The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients receive cetuximab IV weekly over 60-120 minutes. Treatment repeats every week for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Beginning 5-7 days after first cetuximab dose, patients undergo IMRT 5 fractions per week for up to 7 weeks.
Biological: Cetuximab · Radiation: Intensity-Modulated Radiation Therapy · Other: Laboratory Biomarker Analysis · Other: Quality-of-Life Assessment · Other: Questionnaire Administration
Patients receive durvalumab IV over 60 minutes every 4 weeks. Treatment repeats every 4 weeks for up to 7 cycles in the absence of disease progression or unacceptable toxicity. Beginning week 2, patients undergo IMRT 5 fractions per week for up to 7 weeks.
Biological: Durvalumab · Radiation: Intensity-Modulated Radiation Therapy · Other: Laboratory Biomarker Analysis · Other: Quality-of-Life Assessment · Other: Questionnaire Administration
Given IV
Also known as: C 225, C-225, C225, Cetuximab Biosimilar CDP-1, Cetuximab Biosimilar CMAB009, Cetuximab Biosimilar KL 140, Chimeric Anti-EGFR Monoclonal Antibody, Chimeric MoAb C225, Chimeric Monoclonal Antibody C225, Erbitux, IMC-C225
Given IV
Also known as: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI 4736, MEDI-4736, MEDI4736
Undergo IMRT
Also known as: IMRT, Intensity modulated radiation therapy (procedure), Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy
Correlative studies
Ancillary studies
Also known as: Quality of Life Assessment
Ancillary studies
Number of Participants With Dose-limiting Toxicity (DLT) [Lead-in Phase]
DLTs were collected to verify the safety of durvalumab with RT in this population. Safety was determined if ≤ 2 of 8 participants in the cohort had any DLT, in which case the study would proceed to phase II with that dose schedule (DS). The probability for the DS to be deemed too toxic, given a true toxicity rate ≥ 45%, is at least 78%. With a true toxicity rate ≤ 20%, the probability for the DS do be deemed safe is 80%. The full DLT definition does not fit here, but includes all grade 5 AEs, grade 3 or 4 AEs definitely or probably related to durvalumab (DPRD) except for specified AEs and situations, and incomplete or \> 2-week delay completing RT due to immune toxicity DPRD. AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, which grade severity from 1=mild to 5=death. Two alternate DSs with a delayed 2nd dose (to reduce/avoid doses concurrent with RT) would be tried if the initial DS was too toxic.
Time frame: From start of durvalumab to 4 weeks after radiation therapy, approximately 13 weeks. Weekly during RT, at RT end, prior to adjuvant durvalumab, one month after end of RT.
Progression-free Survival (Percentage of Participants Alive Without Progression) [Phase II Primary]
Progression (failure) is defined as local, regional, or distant disease progression, or death from any cause. Progression was assessed by imaging, clinical assessment, or biopsy. Failure time is defined as time from randomization to failure or last follow-up (censored). Failure rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year estimates are provided. Analysis was planned to occur after 69 failure events had been reported.
Time frame: From randomization to last follow-up: weekly during RT, after end of RT: every 4 months for 1 year, every 6 months for 2 years, then annually. Additionally, every 4 weeks during adjuvant durvalumab. Maximum follow-up at time of analysis was 4.2 years.
Overall Survival (Percentage of Participants Alive) [Originally Phase III Primary / Now Phase II Secondary]
Overall survival (OS) time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year estimates are provided.
Time frame: From randomization to last follow-up: weekly during RT, after end of RT: every 4 months for 1 year, every 6 months for 2 years, then annually. Additionally, every 4 weeks during adjuvant durvalumab. Maximum follow-up at time of analysis was 4.2 years.
Locoregional Failure (Percentage of Participants With Locoregional Failure)
Locoregional progression is defined as local or regional progression or recurrence, death due to study cancer or unknown causes without documented progression. Progression was assessed by imaging, clinical assessment, or biopsy. Failure time is defined as time from randomization to failure, distant metastasis (competing risk), deaths from other causes (competing risk), or last follow-up (censored). Failure rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year estimates are provided.
Time frame: From randomization to last follow-up: weekly during RT, after end of RT: every 4 months for 1 year, every 6 months for 2 years, then annually. Additionally, every 4 weeks during adjuvant durvalumab. Maximum follow-up at time of analysis was 4.2 years.
Distant Metastasis (Percentage of Participants With Distant Metastasis)
Failure is defined as the occurrence of distant metastasis. Failure time is defined as time from randomization to first occurrence of distant metastasis, local or regional progression or recurrence (competing risk), death (competing risk), or last follow-up (censored). Failure rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year estimates are provided.
Time frame: From randomization to last follow-up: weekly during RT, after end of RT: every 4 months for 1 year, every 6 months for 2 years, then annually. Additionally, every 4 weeks during adjuvant durvalumab. Maximum follow-up at time of analysis was 4.2 years.
Competing Mortality (Percentage of Participants Who Died Due to Causes Other Than Study Cancer)
Failure is defined as Death from second primary, protocol treatment, or "other cause". Failure time is defined as time from randomization to first occurrence of failure, death due to study cancer or unknown cause (competing risk), or last follow-up (censored). Failure rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year estimates are provided.
Time frame: From randomization to last follow-up: weekly during RT, after end of RT: every 4 months for 1 year, every 6 months for 2 years, then annually. Additionally, every 4 weeks during adjuvant durvalumab. Maximum follow-up at time of analysis was 4.2 years.
Percentage of Participants With Complete or Partial Response at 4-month Scan Determined by Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1
Fludeoxyglucose F-18 positron emission tomography/computed tomography (FDG-PET/CT) scans at baseline and four months after the end of radiation therapy are compared. Per RECIST 1.1: * Complete response: * Disappearance of all lesions and pathologic lymph nodes * Partial response: * ≥ 30% decrease sum of the longest diameters * No new lesions * No progression of non-target lesions
Time frame: Baseline and 4 months after end of RT (approximately 6.5 months)
Number of Participants by Highest Grade Adverse Event Reported
Common Terminology Criteria for Adverse Events (version 5.0) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.
Time frame: From randomization to last follow-up: weekly during RT, RT end, from end of RT: months 1, (Cetuximab: 2, 3,) 4, 8, 12, 18, 24, 30, 36, then annually. Additionally, prior to each adjuvant durvalumab cycle. Maximum follow-up at time of analysis= 4.2 yr.
Change in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30) Physical Functioning Score at One Year
The EORTC QLQ C30 Physical Functioning score measures patient reported limitations in physical activities. Possible scores for each score range from 0 to 100, with higher scores indicating better physical functioning. Change is defined as the time point score minus the baseline score, where positive values indicate improvement for and negative values indicate.
Time frame: Baseline and one year after end of radiation therapy (approximately 7 weeks)
Change in MD Anderson Dysphagia Inventory (MDADI) Composite Score at One Year
The MDADI Composite score measures overall swallowing related quality of life derived from the emotional, functional, and physical scores, excluding the global item. Possible scores range from 20 to 100, with higher scores indicating better swallowing related quality of life. Change is defined as the time point score minus the baseline score, where positive values indicate improvement and negative values indicate decline.
Time frame: Baseline and one year after end of radiation therapy (approximately 7 weeks)
Change in Performance Status Scale for Head and Neck Cancer (PSS HN) Normalcy of Diet Score at One Year
The PSS HN Normalcy of Diet score measures clinician rated normalcy of diet. Possible scores range from 0 to 100, with higher scores indicating better dietary function. Change is defined as the time point score minus the baseline score, where positive values indicate improvement and negative values indicate worsening function.
Time frame: Baseline and one year after end of radiation therapy (approximately 7 weeks)
Change in PSS HN Eating in Public Score at One Year
The PSS HN Eating in Public score measures clinician rated public eating. Possible scores range from 0 to 100, with higher scores indicating better eating function. Change is defined as the time point score minus the baseline score, where positive values indicate improvement and negative values indicate worsening function.
Time frame: Baseline and one year after end of radiation therapy (approximately 7 weeks)
Change in PSS HN Understandability of Speech Score at One Year
The PSS HN Understandability of Speech score measures clinician rated speech. Possible scores range from 0 to 100, with higher scores indicating better speech function. Change is defined as the time point score minus the baseline score, where positive values indicate improvement and negative values indicate worsening function.
Time frame: Baseline and one year after end of radiation therapy (approximately 7 weeks)
Progression-free Survival (Percentage of Participants Alive Without Progression) by Baseline PD-L1 (Programmed Cell Death Ligand 1) Expression
Failure for progression-free survival is defined as local, regional, or distant disease progression, or death from any cause. Progression was assessed by imaging, clinical assessment, or biopsy. Failure time is defined as time from randomization to failure or last follow-up (censored). PD-L1 expression is defined by a combined positive score (CPS) ≥ 1, assessed by masked central analysis of baseline tissue specimens. CPS = \[(number of tumor cells positive for PD-L1) / (number of tumor cells positive for PD-L1 + number of tumor cells negative for PD-L1)\] multiplied by 100, yielding a possible score of 0 to 100. Treatment effect hazard ratios within PD-L1 subgroup were estimated by Cox proportional hazards model and progression-free survival estimates were estimated by Kaplan-Meier method. Analysis was planned to occur after 69 failure events had been reported and tissue specimen analysis was complete.
Time frame: From randomization to date of progression or last follow-up, whichever occurs first. Maximum follow-up at time of analysis was 4.2 years. Two-year PFS estimates are reported.
Progression-free Survival (Percentage of Participants Alive Without Progression) by Baseline p16 Status
Failure for progression-free survival is defined as local, regional, or distant disease progression, or death from any cause. Progression was assessed by imaging, clinical assessment, or biopsy. Failure time is defined as time from randomization to failure or last follow-up (censored). Positive p16 status was defined as more than 70% strong nuclear or nuclear and cytoplasmic staining of tumor cells, confirmed by central pathology review. Treatment effect hazard ratios within p16 subgroup were estimated by Cox proportional hazards model and progression-free survival estimates were estimated by Kaplan-Meier method. Analysis was planned to occur after 69 failure events had been reported and tissue specimen analysis was complete.
Time frame: From randomization to date of progression or last follow-up, whichever occurs first. Maximum follow-up at time of analysis was 4.2 years. Two-year PFS estimates are reported.
Change in the EORTC QLQ C30 Global Heath Status Score at One Year
The EORTC QLQ C30 Global Heath Status score measures overall health related quality of life. Possible scores for each scale range from 0 to 100, with higher scores indicate better overall quality of life. Change is defined as the time point score minus the baseline score, where positive values indicate improvement for and negative values indicate.
Time frame: Baseline and one year
Change in the EORTC QLQ C30 Fatigue Score at One Year
The EORTC QLQ C30 fatigue score measures patient reported fatigue symptom burden. Possible scores for each score range from 0 to 100, with higher scores indicating worse fatigue. Change is defined as the time point score minus the baseline score, where negative values indicate improvement for and positive values indicate.
Time frame: Baseline and one year
Change in EORTC QLQ-C30 H&N35 Swallowing Score at One Year
The EORTC QLQ-H\&N35 swallowing score measures patient-reported difficulty with swallowing various foods and liquid and ranges from 0 (no swallowing problems) to 100 (maximum swallowing difficulty). A positive change from baseline indicates worsening swallowing function.
Time frame: Baseline and one year
Change in MDADI Global Score at One Year
The MDADI Global score measures patient reported overall swallowing related quality of life. Possible scores range from 20 to 100, with higher scores indicating better swallowing related quality of life. Change is defined as the time point score minus the baseline score, where positive values indicate improvement and negative values indicate decline.
Time frame: Baseline and one year
Change in MDADI Emotional Score at One Year
The MDADI Emotional score measures the emotional impact of swallowing difficulties on quality of life. Possible scores range from 20 to 100, with higher scores indicating better swallowing related quality of life. Change is defined as the time point score minus the baseline score, where positive values indicate improvement and negative values indicate decline.
Time frame: Baseline and one year
Change in MDADI Functional Score at One Year
The MDADI Functional score measures the functional impact of swallowing difficulties on daily activities. Possible scores range from 20 to 100, with higher scores indicating better swallowing related quality of life. Change is defined as the time point score minus the baseline score, where positive values indicate improvement and negative values indicate decline.
Time frame: Baseline and one year
Change in MDADI Physical Score at One Year
The MDADI Physical score measures the physical aspects of swallowing difficulties and their impact on swallowing related quality of life. Possible scores range from 20 to 100, with higher scores indicating better swallowing related quality of life. Change is defined as the time point score minus the baseline score, where positive values indicate improvement and negative values indicate decline.
Time frame: Baseline and one year
Change in EuroQol 5 Dimension 5 Level (EQ 5D 5L) Index Score at One Year
The EQ-5D-5L Index score measures health related quality of life based on responses to five dimensions: mobility, self care, usual activities, pain/discomfort, and anxiety/depression. Possible scores range from 0 (worst health state) to 1(best health state). Change is defined as the time point score minus the baseline score, where positive values indicate improvement and negative values indicate decline.
Time frame: Baseline and 1 year
Change in EQ 5D 5L Visual Analogue Scale at One Year
The EQ 5D 5L Visual Analogue Scale measures self rated overall health on a vertical visual analogue scale. Possible scores range from 0 for the worst imaginable health state) to 100 for the best imaginable health state. Change is defined as the time point score minus the baseline score, where positive values indicate improvement and negative values indicate decline.
Time frame: Baseline and 1 year
Secondary Biomarker Analysis
Will perform multiparametric flow cytometry on peripheral mononuclear cells (PBMC) from patient-derived blood samples to quantify changes in immune cell frequency and activation status before, during and after radiation combined with cetuximab or radiation combined with durvalumab. To assess the statistical significance of pre- to post-treatment changes in levels of immunoglobulin (Ig)Gs as well as other markers, normalized signal intensities (log2) will be tested using a paired t test within an arm and two sample t test between the two arms. If the distribution assumption is violated for the t tests, nonparametric tests, such as the Wilcoxon signed-rank test will be considered. Lastly, the association between PFS and OS and post-treatment changes in frequency and activation state of T-cells, clonality and diversity of T cell receptor (TCR), and IgG levels will be evaluated using a two-sided Wald test at 0.05 level on the basis of Cox models.
Time frame: Baseline up to 4 months after RT
Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE)
PRO-CTCAE is not intended for expedited reporting, real time review or safety reporting. PRO-CTCAE data are exploratory and not currently intended for use in data safety monitoring or adverse event stopping rules.
Time frame: Up to 3 years
QOL Endpoints Using Other Items in EORTC QLQ/HN35, EQ5D and MDADI Subscales
The mean change from baseline at each time point will be summarized using mean and standard deviations for each arm. Mean change from baseline will be compared between the arms using a two sample t test. If data normality assumptions are not met, the Wilcoxon rank sum test will be used to test the hypothesis. Mean change from baseline will be tested using an omnibus F test followed by individual comparisons of change scores at different time points within each treatment group. The same analysis will be conducted for between group comparisons at each time point.
Time frame: Up to 12-24 months from end of RT
| Milestone | (Lead-in) RT + Durvalumab | RT + Cetuximab | RT + Durvalumab |
|---|---|---|---|
| Started | 10 | 0 | 0 |
| Started treatment | 10 | 0 | 0 |
| Completed | 10 | 0 | 0 |
| Not completed | 0 | 0 | 0 |
| Milestone | (Lead-in) RT + Durvalumab | RT + Cetuximab | RT + Durvalumab |
|---|---|---|---|
| Started | 0 | 63 | 123 |
| Started treatment | 0 | 61 | 119 |
| Completed | 0 | 63 | 123 |
| Not completed | 0 | 0 | 0 |
DLTs were collected to verify the safety of durvalumab with RT in this population. Safety was determined if ≤ 2 of 8 participants in the cohort had any DLT, in which case the study would proceed to phase II with that dose schedule (DS). The probability for the DS to be deemed too toxic, given a true toxicity rate ≥ 45%, is at least 78%. With a true toxicity rate ≤ 20%, the probability for the DS do be deemed safe is 80%. The full DLT definition does not fit here, but includes all grade 5 AEs, grade 3 or 4 AEs definitely or probably related to durvalumab (DPRD) except for specified AEs and situations, and incomplete or \> 2-week delay completing RT due to immune toxicity DPRD. AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, which grade severity from 1=mild to 5=death. Two alternate DSs with a delayed 2nd dose (to reduce/avoid doses concurrent with RT) would be tried if the initial DS was too toxic.
| Participants | (Lead-in) RT + Durvalumab |
|---|---|
| Number of Participants With Dose-limiting Toxicity (DLT) [Lead-in Phase] | 0 |
Progression (failure) is defined as local, regional, or distant disease progression, or death from any cause. Progression was assessed by imaging, clinical assessment, or biopsy. Failure time is defined as time from randomization to failure or last follow-up (censored). Failure rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year estimates are provided. Analysis was planned to occur after 69 failure events had been reported.
| percentage of participants | RT + Cetuximab | RT + Durvalumab |
|---|---|---|
| Progression-free Survival (Percentage of Participants Alive Without Progression) [Phase II Primary] | 63.7 (51.3 to 76.1) | 50.6 (41.5 to 59.8) |
Overall survival (OS) time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year estimates are provided.
| percentage of participants | RT+ Cetuximab | RT + Durvalumab |
|---|---|---|
| Overall Survival (Percentage of Participants Alive) [Originally Phase III Primary / Now Phase II Secondary] | 77.5 (66.7 to 88.3) | 69.3 (60.8 to 77.8) |
Locoregional progression is defined as local or regional progression or recurrence, death due to study cancer or unknown causes without documented progression. Progression was assessed by imaging, clinical assessment, or biopsy. Failure time is defined as time from randomization to failure, distant metastasis (competing risk), deaths from other causes (competing risk), or last follow-up (censored). Failure rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year estimates are provided.
| percentage of participants | RT+ Cetuximab | RT + Durvalumab |
|---|---|---|
| Locoregional Failure (Percentage of Participants With Locoregional Failure) | 18.9 (10.0 to 29.9) | 31.3 (23.0 to 40.0) |
Failure is defined as the occurrence of distant metastasis. Failure time is defined as time from randomization to first occurrence of distant metastasis, local or regional progression or recurrence (competing risk), death (competing risk), or last follow-up (censored). Failure rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year estimates are provided.
| percentage of participants | RT+ Cetuximab | RT + Durvalumab |
|---|---|---|
| Distant Metastasis (Percentage of Participants With Distant Metastasis) | 12.1 (5.3 to 22.0) | 9.5 (5.0 to 15.7) |
Failure is defined as Death from second primary, protocol treatment, or "other cause". Failure time is defined as time from randomization to first occurrence of failure, death due to study cancer or unknown cause (competing risk), or last follow-up (censored). Failure rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year estimates are provided.
| percentage of participants | RT+ Cetuximab | RT + Durvalumab |
|---|---|---|
| Competing Mortality (Percentage of Participants Who Died Due to Causes Other Than Study Cancer) | 5.3 (1.4 to 13.4) | 10.5 (5.7 to 17.0) |
Fludeoxyglucose F-18 positron emission tomography/computed tomography (FDG-PET/CT) scans at baseline and four months after the end of radiation therapy are compared. Per RECIST 1.1: * Complete response: * Disappearance of all lesions and pathologic lymph nodes * Partial response: * ≥ 30% decrease sum of the longest diameters * No new lesions * No progression of non-target lesions
| percentage of participants | RT+ Cetuximab | RT + Durvalumab |
|---|---|---|
| Percentage of Participants With Complete or Partial Response at 4-month Scan Determined by Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 | 72.7 (51.8 to 86.8) | 75.9 (57.9 to 87.8) |
Common Terminology Criteria for Adverse Events (version 5.0) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.
| Participants | RT+ Cetuximab | RT + Durvalumab |
|---|---|---|
| < Grade 3 | 12 | 36 |
| Grade 3 | 37 | 57 |
| Grade 4 | 11 | 15 |
| Grade 5 | 1 | 11 |
The EORTC QLQ C30 Physical Functioning score measures patient reported limitations in physical activities. Possible scores for each score range from 0 to 100, with higher scores indicating better physical functioning. Change is defined as the time point score minus the baseline score, where positive values indicate improvement for and negative values indicate.
| score on a scale | RT+ Cetuximab | RT + Durvalumab |
|---|---|---|
| Change in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30) Physical Functioning Score at One Year | -1.90 (-12.24 to 8.43) | -1.49 (-6.23 to 3.24) |
The MDADI Composite score measures overall swallowing related quality of life derived from the emotional, functional, and physical scores, excluding the global item. Possible scores range from 20 to 100, with higher scores indicating better swallowing related quality of life. Change is defined as the time point score minus the baseline score, where positive values indicate improvement and negative values indicate decline.
| score on a scale | RT + Cetuximab | RT + Durvalumab |
|---|---|---|
| Change in MD Anderson Dysphagia Inventory (MDADI) Composite Score at One Year | -0.62 (-5.91 to 4.66) | -3.48 (-8.05 to 1.09) |
The PSS HN Normalcy of Diet score measures clinician rated normalcy of diet. Possible scores range from 0 to 100, with higher scores indicating better dietary function. Change is defined as the time point score minus the baseline score, where positive values indicate improvement and negative values indicate worsening function.
| score on a scale | RT + Cetuximab | RT + Durvalumab |
|---|---|---|
| Change in Performance Status Scale for Head and Neck Cancer (PSS HN) Normalcy of Diet Score at One Year | -2.27 (-14.66 to 10.11) | -6.47 (-15.05 to 2.11) |
The PSS HN Eating in Public score measures clinician rated public eating. Possible scores range from 0 to 100, with higher scores indicating better eating function. Change is defined as the time point score minus the baseline score, where positive values indicate improvement and negative values indicate worsening function.
| score on a scale | RT + Cetuximab | RT + Durvalumab |
|---|---|---|
| Change in PSS HN Eating in Public Score at One Year | -11.36 (-24.04 to 1.31) | -8.82 (-17.47 to -0.17) |
The PSS HN Understandability of Speech score measures clinician rated speech. Possible scores range from 0 to 100, with higher scores indicating better speech function. Change is defined as the time point score minus the baseline score, where positive values indicate improvement and negative values indicate worsening function.
| score on a scale | RT + Cetuximab | RT + Durvalumab |
|---|---|---|
| Change in PSS HN Understandability of Speech Score at One Year | -3.41 (-9.62 to 2.80) | -8.82 (-16.11 to -1.54) |
Failure for progression-free survival is defined as local, regional, or distant disease progression, or death from any cause. Progression was assessed by imaging, clinical assessment, or biopsy. Failure time is defined as time from randomization to failure or last follow-up (censored). PD-L1 expression is defined by a combined positive score (CPS) ≥ 1, assessed by masked central analysis of baseline tissue specimens. CPS = \[(number of tumor cells positive for PD-L1) / (number of tumor cells positive for PD-L1 + number of tumor cells negative for PD-L1)\] multiplied by 100, yielding a possible score of 0 to 100. Treatment effect hazard ratios within PD-L1 subgroup were estimated by Cox proportional hazards model and progression-free survival estimates were estimated by Kaplan-Meier method. Analysis was planned to occur after 69 failure events had been reported and tissue specimen analysis was complete.
| percentage of participants | RT + Cetuximab | RT + Durvalumab |
|---|---|---|
| CPS ≥ 1 (PD-L1 expression) | 59.9 (43.6 to 76.2) | 54.8 (43.9 to 65.6) |
| CPS = 0 (no PD-L1 expression) | 61.5 (35.1 to 88.0) | 30.0 (9.9 to 50.1) |
Failure for progression-free survival is defined as local, regional, or distant disease progression, or death from any cause. Progression was assessed by imaging, clinical assessment, or biopsy. Failure time is defined as time from randomization to failure or last follow-up (censored). Positive p16 status was defined as more than 70% strong nuclear or nuclear and cytoplasmic staining of tumor cells, confirmed by central pathology review. Treatment effect hazard ratios within p16 subgroup were estimated by Cox proportional hazards model and progression-free survival estimates were estimated by Kaplan-Meier method. Analysis was planned to occur after 69 failure events had been reported and tissue specimen analysis was complete.
| percentage of participants | RT + Cetuximab | RT + Durvalumab |
|---|---|---|
| p16-positive | 74.8 (59.6 to 89.9) | 68.8 (57.4 to 80.1) |
| p16-negative | 48.1 (27.6 to 68.5) | 23.2 (10.1 to 36.3) |
The EORTC QLQ C30 Global Heath Status score measures overall health related quality of life. Possible scores for each scale range from 0 to 100, with higher scores indicate better overall quality of life. Change is defined as the time point score minus the baseline score, where positive values indicate improvement for and negative values indicate.
Results for this outcome have not been posted.
The EORTC QLQ C30 fatigue score measures patient reported fatigue symptom burden. Possible scores for each score range from 0 to 100, with higher scores indicating worse fatigue. Change is defined as the time point score minus the baseline score, where negative values indicate improvement for and positive values indicate.
Results for this outcome have not been posted.
The EORTC QLQ-H\&N35 swallowing score measures patient-reported difficulty with swallowing various foods and liquid and ranges from 0 (no swallowing problems) to 100 (maximum swallowing difficulty). A positive change from baseline indicates worsening swallowing function.
Results for this outcome have not been posted.
The MDADI Global score measures patient reported overall swallowing related quality of life. Possible scores range from 20 to 100, with higher scores indicating better swallowing related quality of life. Change is defined as the time point score minus the baseline score, where positive values indicate improvement and negative values indicate decline.
Results for this outcome have not been posted.
The MDADI Emotional score measures the emotional impact of swallowing difficulties on quality of life. Possible scores range from 20 to 100, with higher scores indicating better swallowing related quality of life. Change is defined as the time point score minus the baseline score, where positive values indicate improvement and negative values indicate decline.
Results for this outcome have not been posted.
The MDADI Functional score measures the functional impact of swallowing difficulties on daily activities. Possible scores range from 20 to 100, with higher scores indicating better swallowing related quality of life. Change is defined as the time point score minus the baseline score, where positive values indicate improvement and negative values indicate decline.
Results for this outcome have not been posted.
The MDADI Physical score measures the physical aspects of swallowing difficulties and their impact on swallowing related quality of life. Possible scores range from 20 to 100, with higher scores indicating better swallowing related quality of life. Change is defined as the time point score minus the baseline score, where positive values indicate improvement and negative values indicate decline.
Results for this outcome have not been posted.
The EQ-5D-5L Index score measures health related quality of life based on responses to five dimensions: mobility, self care, usual activities, pain/discomfort, and anxiety/depression. Possible scores range from 0 (worst health state) to 1(best health state). Change is defined as the time point score minus the baseline score, where positive values indicate improvement and negative values indicate decline.
Results for this outcome have not been posted.
The EQ 5D 5L Visual Analogue Scale measures self rated overall health on a vertical visual analogue scale. Possible scores range from 0 for the worst imaginable health state) to 100 for the best imaginable health state. Change is defined as the time point score minus the baseline score, where positive values indicate improvement and negative values indicate decline.
Results for this outcome have not been posted.
Will perform multiparametric flow cytometry on peripheral mononuclear cells (PBMC) from patient-derived blood samples to quantify changes in immune cell frequency and activation status before, during and after radiation combined with cetuximab or radiation combined with durvalumab. To assess the statistical significance of pre- to post-treatment changes in levels of immunoglobulin (Ig)Gs as well as other markers, normalized signal intensities (log2) will be tested using a paired t test within an arm and two sample t test between the two arms. If the distribution assumption is violated for the t tests, nonparametric tests, such as the Wilcoxon signed-rank test will be considered. Lastly, the association between PFS and OS and post-treatment changes in frequency and activation state of T-cells, clonality and diversity of T cell receptor (TCR), and IgG levels will be evaluated using a two-sided Wald test at 0.05 level on the basis of Cox models.
Results for this outcome have not been posted.
PRO-CTCAE is not intended for expedited reporting, real time review or safety reporting. PRO-CTCAE data are exploratory and not currently intended for use in data safety monitoring or adverse event stopping rules.
Results for this outcome have not been posted.
The mean change from baseline at each time point will be summarized using mean and standard deviations for each arm. Mean change from baseline will be compared between the arms using a two sample t test. If data normality assumptions are not met, the Wilcoxon rank sum test will be used to test the hypothesis. Mean change from baseline will be tested using an omnibus F test followed by individual comparisons of change scores at different time points within each treatment group. The same analysis will be conducted for between group comparisons at each time point.
Results for this outcome have not been posted.
Collected over Weekly during RT, RT end, from end of RT: months 1, (Cetuximab: 2, 3,) 4, 8, 12, 18, 24, 30, 36, then annually. Additionally, prior to each adjuvant durvalumab cycle. Maximum follow-up at time of analysis= 4.2 yr.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| (Lead-in) RT + Durvalumab | 3/10 (30%) | 4/10 (40%) | 10/10 (100%) |
| RT + Cetuximab | 17/63 (27%) | 51/61 (83.6%) | 61/61 (100%) |
| RT + Durvalumab | 41/123 (33.3%) | 84/119 (70.6%) | 118/119 (99.2%) |
| Event | (Lead-in) RT + Durvalumab | RT + Cetuximab | RT + Durvalumab |
|---|---|---|---|
| Lymphocyte count decreasedInvestigations | 0/10 | 19/61 | 30/119 |
| DysphagiaGastrointestinal disorders | 0/10 | 18/61 | 25/119 |
| Mucositis oralGastrointestinal disorders | 0/10 | 11/61 | 14/119 |
| AnorexiaMetabolism and nutrition disorders | 0/10 | 7/61 | 17/119 |
| Dermatitis radiationInjury, poisoning and procedural complications | 0/10 | 8/61 | 6/119 |
| Oral hemorrhageGastrointestinal disorders | 1/10 | 0/61 | 0/119 |
| Lung infectionInfections and infestations | 1/10 | 0/61 | 0/119 |
| AnxietyPsychiatric disorders | 1/10 | 0/61 | 0/119 |
| DepressionPsychiatric disorders | 1/10 | 0/61 | 0/119 |
| Suicidal ideationPsychiatric disorders | 1/10 | 0/61 | 0/119 |
| Event | (Lead-in) RT + Durvalumab | RT + Cetuximab | RT + Durvalumab |
|---|---|---|---|
| Dry mouthGastrointestinal disorders | 10/10 | 0/61 | 0/119 |
| DysphagiaGastrointestinal disorders | 9/10 | 0/61 | 0/119 |
| Dermatitis radiationInjury, poisoning and procedural complications | 9/10 | 0/61 | 0/119 |
| FatigueGeneral disorders | 0/10 | 52/61 | 98/119 |
| DysphagiaGastrointestinal disorders | 0/10 | 47/61 | 97/119 |
| Weight lossInvestigations | 8/10 | 0/61 | 0/119 |
| Mucositis oralGastrointestinal disorders | 0/10 | 46/61 | 85/119 |
| Dermatitis radiationInjury, poisoning and procedural complications | 0/10 | 44/61 | 83/119 |
| Dry mouthGastrointestinal disorders | 0/10 | 37/61 | 84/119 |
| Mucositis oralGastrointestinal disorders | 7/10 | 0/61 | 0/119 |
Enrolled participants (i.e. for phase II, randomized)
| Age, Customized(Participants) | (Lead-in) RT + Durvalumab | RT + Cetuximab | RT + Durvalumab | Total |
|---|---|---|---|---|
| ≤ 49 years | 1 | 1 | 2 | 4 |
| 50 - 59 years | 0 | 9 | 10 | 19 |
| 60 - 69 years | 6 | 20 | 35 | 61 |
| 70 - 79 years | 3 | 25 | 60 | 88 |
| ≥ 80 years | 0 | 8 | 16 | 24 |
| Sex: Female, Male(Participants) | (Lead-in) RT + Durvalumab | RT + Cetuximab | RT + Durvalumab | Total |
|---|---|---|---|---|
| Female | 1 | 9 | 21 | 31 |
| Male | 9 | 54 | 102 | 165 |
| Ethnicity (NIH/OMB)(Participants) | (Lead-in) RT + Durvalumab | RT + Cetuximab | RT + Durvalumab | Total |
|---|---|---|---|---|
| Hispanic or Latino | 10 | 3 | 1 | 14 |
| Not Hispanic or Latino | 0 | 56 | 117 | 173 |
| Unknown or Not Reported | 0 | 4 | 5 | 9 |
| Race (NIH/OMB)(Participants) | (Lead-in) RT + Durvalumab | RT + Cetuximab | RT + Durvalumab | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 1 | 1 | 2 |
| Asian | 0 | 1 | 2 | 3 |
| Native Hawaiian or Other Pacific Islander | 0 | 1 | 0 | 1 |
| Black or African American | 0 | 6 | 11 | 17 |
| White | 10 | 50 | 105 | 165 |
| More than one race | 0 | 0 | 1 | 1 |
| Unknown or Not Reported | 0 | 4 | 3 | 7 |
| Zubrod performance status(Participants) | (Lead-in) RT + Durvalumab | RT + Cetuximab | RT + Durvalumab | Total |
|---|---|---|---|---|
| 0 | 4 | 28 | 48 | 80 |
| 1 | 6 | 27 | 60 | 93 |
| 2 | 0 | 8 | 15 | 23 |
| Modified Charlson Comorbidity Index (CCI)(Participants) | (Lead-in) RT + Durvalumab | RT + Cetuximab | RT + Durvalumab | Total |
|---|---|---|---|---|
| 0 (no comorbidities) | 4 | 24 | 43 | 71 |
| ≥ 1 | 6 | 39 | 80 | 125 |
| Primary tumor site and p16 status(Participants) | (Lead-in) RT + Durvalumab | RT + Cetuximab | RT + Durvalumab | Total |
|---|---|---|---|---|
| Oropharynx, p16-positive | 6 | 27 | 55 | 88 |
| Unknown, p16-positive | 0 | 3 | 3 | 6 |
| Oropharynx, p16-negative | 2 | 3 | 15 | 20 |
| Unknown, p16-negative | 0 | 0 | 1 | 1 |
| Oral cavity | 0 | 4 | 6 | 10 |
| Hypopharynx | 0 | 8 | 13 | 21 |
| Larynx | 2 | 18 | 30 | 50 |
| T stage, clinical (AJCC 8)(Participants) | (Lead-in) RT + Durvalumab | RT + Cetuximab | RT + Durvalumab | Total |
|---|---|---|---|---|
| T0 | 0 | 3 | 4 | 7 |
| T1 | 3 | 7 | 11 | 21 |
| T2 | 2 | 16 | 38 | 56 |
| T3 | 3 | 20 | 42 | 65 |
| T4 | 2 | 11 | 15 | 28 |
| T4a | 0 | 6 | 11 | 17 |
| T4b | 0 | 0 | 2 | 2 |
7 further baseline measures are reported on the registry.
Showing the first 100 of 256 sites across 2 countries. Choose a country and city above to see the rest.
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Apr 2018 to primary completion in Sep 2022, 53 months.
Results were first posted in Oct 2023, 1 year 1 month after primary completion.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Durvalumab
National Cancer Institute (NCI) →