CompletedNCT03416153Updated Aug 7, 2026Results posted

Individualized Adaptive De-escalated Radiotherapy for HPV-related Oropharynx Cancer

A Phase 2 interventional study of Carboplatin and Radiation Therapy in Oropharynx Cancer, sponsored by University of Michigan Rogel Cancer Center. Completed at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-07.

Sponsored by University of Michigan Rogel Cancer Center · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 91
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study summary

This prospective study aims to utilize pre- and mid-treatment PET-CT to guide de-escalation of radiation therapy in HPV-related squamous cell carcinoma of the oropharynx.

Conditions studied

Oropharynx Cancer

Browse trials for

Oropharyngeal Neoplasms 372

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Patients must have FDG-avid and histologically or cytologically proven squamous cell carcinoma of the oropharynx (tonsil, base of tongue, oropharyngeal wall, soft palate) that is p16 positive by immunohistochemistry or HPV positive by in situ hybridization.
AJCC eighth edition staging stage 1 and stage 2
Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:
History/physical examination, including documentation of weight within 4 weeks prior to registration;
FDG-PET/CT scan for staging and RT plan within 4 weeks prior to registration;
Zubrod Performance Status (A quantification of the functional status of cancer patients that runs from 0 to 5, with 0 denoting perfect health and 5 death) 0-1 within 4 weeks prior to registration;
Age ≥ 18;
Able to tolerate PET/CT imaging required to be performed
CBC/differential obtained within 4 weeks prior to registration on study, with adequate bone marrow function;
Serum creatinine within normal institutional limits or a creatinine clearance ≥ 45 ml/min within 4 weeks prior to registration;
Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study.
The patient must provide study-specific informed consent prior to study entry.

Exclusion criteria

Exclusion Criteria:

cT4, cN3 or cM1 disease
"Matted nodes" as determined by review with Neuroradiology
Gross total excision of both primary and nodal disease with curative intent; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease. In other words, to participate in this protocol, the patient must have clinically or radiographically evident gross disease for which disease response can be assessed.
Carcinoma of the neck of unknown primary site origin (even if p16 positive);
Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years
Any prior therapy for the study cancer; note that prior chemotherapy for a different cancer is allowable if > 3 years prior to study;
Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields;
Severe, active co-morbidity;
Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception;
Poorly controlled diabetes

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 91 participants (actual)

Study arms

Active comparator
Standard Treatment
Patients will receive a single prescription of 70 Gy in 35 fractions with RT given once daily, 5 days a week along with weekly carboplatin and paclitaxel (standard therapy)
Drug: Carboplatin · Radiation: Radiation Therapy · Drug: Paclitaxel
Experimental
De-escalation Treatment
Patients will initially receive a single prescription of 70 Gy in 35 fractions with RT given once daily, 5 days a week along with weekly carboplatin and paclitaxel (standard therapy). If certain parameters are met radiation therapy will be reduced to 54Gy to high risk Planned Target Volume (PTV) and 43.2Gy to low risk PTV all in 27 fractions.
Drug: Carboplatin · Radiation: Radiation Therapy · Drug: Paclitaxel

Interventions

DrugCarboplatin
AUC=1 weekly during radiation therapy. Carboplatin will be given once a week in combination with paclitaxel (standard treatment), concurrent with radiation therapy. Given IV.
RadiationRadiation Therapy
Patients will initially receive a single prescription of 70 Gy to PTV1 in 35 fractions with RT given once daily, 5 days a week along with weekly carboplatin and paclitaxel (standard therapy). Dose will be reduced to 54Gy to high risk PTV and 43.2Gy to low risk PTV all in 27 fractions for patients who meet pPET-CT and iPET-CT parameters.
DrugPaclitaxel
30 mg/m2 weekly during radiation therapy. Paclitaxel will be given once a week in combination with carboplatin (standard treatment), concurrent with radiation therapy. Given IV.

What researchers measure

Primary outcomes

The Percentage of Patients With Local Regional Recurrence (LRR) of Disease
RECIST (Response Evaluation Criteria In Solid Tumors) will be used to evaluate response and recurrence. All patients will be analyzed together as the goal of the study is to estimate risk of LRR in this patient population treated with this particular strategy in which some patients continue to receive standard therapy while others are de-escalated. Results will also be estimated and reported separately for patients receiving standard or de-escalated therapy.
Time frame: 1 Year
Change in Metabolic Tumor Volume 50% (MTV 50%)
The change in metabolic tumor volume (MTV)50% at the mid-treatment timepoint will be calculated as percent change from baseline and used as a continuous variable in a Cox model for an outcome of time to LRR. Will also evaluate more non-parametrically, the relation between hazard of LRR and mid-treatment MTV50% using a kernel estimator in a Cox model.
Time frame: 2 months

Secondary outcomes

Patterns of Failure
Kaplan-Meier estimate of the percentage of participants who experienced Locoregional relapse versus distant relapse
Time frame: at 3 months and 2 years
Overall Survival
Kaplan-Meier estimate of the percentage of participants who are still alive at 3 months and 2 years.
Time frame: at 3 months, and 2 Years
Progression- Free Survival
Kaplan-Meier estimate of the percentage of participants who are still in progression free survival at 3 months and 2 years
Time frame: at 3 months and 2 years
Incidence of Toxicity
Toxicity outcomes will be estimated as proportions of patients with available toxicity data at 1, 3 and 12 months. XQ, Xerostomia Questionnaire, is scored on a scale of 0-100 with higher score indicating worse xerostomia. HN, FACT-HN, is scored on a scale of 0-190 with higher score indicating a better quality of life.
Time frame: 1, 3 and 12 months
Detectable Circulating Tumor Deoxyribonucleic Acid (ctDNA) in Participants
Median values of ctDNA molecules present throughout the study. The week 6/7 measurement is taken as the first measurement that was available during weeks 6 and 7 to minimize missing data and to account for minor timing deviations in sample collection during weeks 6 and 7
Time frame: from Baseline up to 7 weeks

Other outcomes

Quality of Life Assessed Per the Functional Assessment of Cancer Therapy-Head and Neck (FACTHN)
Quality of life (QOL) outcomes and swallowing study results will be summarized descriptively by timepoint. If there is substantial missingness in the QOL outcomes the study will assess for informative missingness by comparing earlier QOL scores and change in earlier QOL scores between patients missing QOL at later time points (e.g. 1 or 2 years).
Time frame: 2 Years

Results

Posted May 22, 2025

Participant flow

Participant flow — Overall Study
Milestone	Standard Treatment	De-escalation Treatment
Started	49	36
Completed	47	35
Not completed	2	1
Withdrew: Physician decision	1	1
Withdrew: Withdrawal by subject	1	0

Outcome measures

PrimaryThe Percentage of Patients With Local Regional Recurrence (LRR) of Disease

RECIST (Response Evaluation Criteria In Solid Tumors) will be used to evaluate response and recurrence. All patients will be analyzed together as the goal of the study is to estimate risk of LRR in this patient population treated with this particular strategy in which some patients continue to receive standard therapy while others are de-escalated. Results will also be estimated and reported separately for patients receiving standard or de-escalated therapy.

Time frame:: 1 Year
Reported as:: Number · percentage of participants

The Percentage of Patients With Local Regional Recurrence (LRR) of Disease
percentage of participants	Standard Treatment	De-escalation Treatment
The Percentage of Patients With Local Regional Recurrence (LRR) of Disease	2 (0 to 6)	3 (0 to 8)

PrimaryChange in Metabolic Tumor Volume 50% (MTV 50%)

The change in metabolic tumor volume (MTV)50% at the mid-treatment timepoint will be calculated as percent change from baseline and used as a continuous variable in a Cox model for an outcome of time to LRR. Will also evaluate more non-parametrically, the relation between hazard of LRR and mid-treatment MTV50% using a kernel estimator in a Cox model.

Time frame:: 2 months
Reported as:: Mean · percent change from baseline

Change in Metabolic Tumor Volume 50% (MTV 50%)
percent change from baseline	Standard Treatment	De-escalation Treatment
Change in Metabolic Tumor Volume 50% (MTV 50%)	-11.3 ± 66.7	-71.1 ± 16.7

SecondaryPatterns of Failure

Kaplan-Meier estimate of the percentage of participants who experienced Locoregional relapse versus distant relapse

Time frame:: at 3 months and 2 years
Reported as:: Number · Estimate of percentage of participants

Patterns of Failure
Estimate of percentage of participants	Standard Treatment	De-escalation Treatment
3 month Locoregional relapse	0 (0 to 0)	0 (0 to 0)
3 month distant relapse	0 (0 to 0)	0 (0 to 0)
2 year Locoregional relapse	6.8 (0 to 13.9)	9.1 (0 to 18.5)
2 year distant relapse	4.1 (0 to 9.7)	6.4 (0 to 14.6)

SecondaryOverall Survival

Kaplan-Meier estimate of the percentage of participants who are still alive at 3 months and 2 years.

Time frame:: at 3 months, and 2 Years
Reported as:: Number · Estimate of percentage of participants

Overall Survival
Estimate of percentage of participants	Standard Treatment	De-escalation Treatment
3 months	98.0 (94.1 to 100)	100 (100 to 100)
2 years	95.8 (90.2 to 100)	97.0 (91.3 to 100)

SecondaryProgression- Free Survival

Kaplan-Meier estimate of the percentage of participants who are still in progression free survival at 3 months and 2 years

Time frame:: at 3 months and 2 years
Reported as:: Number · Estimate of percentage of participants

Progression- Free Survival
Estimate of percentage of participants	Standard Treatment	De-escalation Treatment
3 months	98.0 (94.1 to 100)	100 (100 to 100)
2 years	87.5 (78.6 to 97.4)	84.7 (73.2 to 98.0)

SecondaryIncidence of Toxicity

Toxicity outcomes will be estimated as proportions of patients with available toxicity data at 1, 3 and 12 months. XQ, Xerostomia Questionnaire, is scored on a scale of 0-100 with higher score indicating worse xerostomia. HN, FACT-HN, is scored on a scale of 0-190 with higher score indicating a better quality of life.

Time frame:: 1, 3 and 12 months
Reported as:: Mean · Estimated mean score

Incidence of Toxicity
Estimated mean score	Standard Treatment	De-escalation Treatment
Xerostomia Questionnaire- 1 month	45 (38.8 to 51.1)	33.3 (26.4 to 40.3)
Xerostomia Questionnaire- 3 months	35.7 (21.2 to 50.1)	36.7 (23.3 to 50.0)
Xerostomia Questionnaire- 12 months	26.6 (19.8 to 33.5)	25.3 (17.7 to 32.9)
FACT-HN- 1 month	26.1 (24.6 to 27.7)	23.1 (21.4 to 24.8)
FACT-HN- 3 months	23.5 (19.9 to 27.1)	20.9 (17.6 to 24.2)
FACT-HN- 12 months	16.9 (15.2 to 18.6)	15.3 (13.4 to 17.2)

SecondaryDetectable Circulating Tumor Deoxyribonucleic Acid (ctDNA) in Participants

Median values of ctDNA molecules present throughout the study. The week 6/7 measurement is taken as the first measurement that was available during weeks 6 and 7 to minimize missing data and to account for minor timing deviations in sample collection during weeks 6 and 7

Time frame:: from Baseline up to 7 weeks
Reported as:: Median · ctDNA targets/mL

Detectable Circulating Tumor Deoxyribonucleic Acid (ctDNA) in Participants
ctDNA targets/mL	Standard Treatment	De-escalation Treatment
Baseline	687 (80 to 2268)	273 (81 to 963)
Week 1	51 (7 to 1231)	66 (29 to 493)
Week 2	174 (67 to 706)	277 (74 to 681)
Week 3	119 (8 to 648)	58 (0 to 414)
Week 4	8 (0 to 133)	0 (0 to 4)
Week 5	0 (0 to 10)	0 (0 to 0)
Week 6/7	0 (0 to 0)	0 (0 to 0)

Other pre-specifiedQuality of Life Assessed Per the Functional Assessment of Cancer Therapy-Head and Neck (FACTHN)

Quality of life (QOL) outcomes and swallowing study results will be summarized descriptively by timepoint. If there is substantial missingness in the QOL outcomes the study will assess for informative missingness by comparing earlier QOL scores and change in earlier QOL scores between patients missing QOL at later time points (e.g. 1 or 2 years).

Time frame:: 2 Years

Results for this outcome have not been posted.

Adverse events

Collected over All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through up to 2 years of follow up, for a median of 36.2 months for Cohort A and 39.6 months for Cohort B.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Standard Treatment	2/49 (4.1%)	5/49 (10.2%)	49/49 (100%)
De-escalation Treatment	1/36 (2.8%)	3/36 (8.3%)	36/36 (100%)

Most frequent serious events

Showing 10 of 12

Most frequent serious events
Event	Standard Treatment	De-escalation Treatment
Cardiac arrestCardiac disorders	2/49	0/36
DysphagiaGastrointestinal disorders	1/49	1/36
HyperglycemiaMetabolism and nutrition disorders	0/49	1/36
Thromboembolic eventVascular disorders	0/49	1/36
Metabolism and nutrition disorders - Other, specifyMetabolism and nutrition disorders	0/49	1/36
AnorexiaMetabolism and nutrition disorders	1/49	0/36
AspirationRespiratory, thoracic and mediastinal disorders	1/49	0/36
DehydrationMetabolism and nutrition disorders	1/49	0/36
Febrile neutropeniaBlood and lymphatic system disorders	1/49	0/36
Lung infectionInfections and infestations	1/49	0/36

Most frequent other events

Showing 10 of 53

Most frequent other events
Event	Standard Treatment	De-escalation Treatment
DysgeusiaGeneral disorders	49/49	35/36
FatigueGeneral disorders	49/49	27/36
Dry mouthGeneral disorders	47/49	33/36
Oral painMusculoskeletal and connective tissue disorders	47/49	26/36
Mucositis oralGastrointestinal disorders	46/49	32/36
Dermatitis radiationSkin and subcutaneous tissue disorders	40/49	27/36
DysphagiaGeneral disorders	38/49	25/36
Weight lossInvestigations	36/49	20/36
PainGeneral disorders	32/49	26/36
NauseaGastrointestinal disorders	32/49	22/36

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Standard Treatment	De-escalation Treatment	Total
<=18 years	0	0	0
Between 18 and 65 years	31	23	54
>=65 years	18	13	31

Sex: Female, Male
Sex: Female, Male(Participants)	Standard Treatment	De-escalation Treatment	Total
Female	6	2	8
Male	43	34	77

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Standard Treatment	De-escalation Treatment	Total
Hispanic or Latino	0	0	0
Not Hispanic or Latino	47	36	83
Unknown or Not Reported	2	0	2

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Standard Treatment	De-escalation Treatment	Total
American Indian or Alaska Native	0	0	0
Asian	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	1	2	3
White	47	33	80
More than one race	0	1	1
Unknown or Not Reported	1	0	1

Region of Enrollment
Region of Enrollment(participants)	Standard Treatment	De-escalation Treatment	Total
United States	49	36	85

Study locations

2 sites

University of Michigan Hospital
Ann Arbor, Michigan 48109, United States
VA Ann Arbor Healthcare System
Ann Arbor, Michigan 48109, United States

References and documents

Study documents

Protocol and statistical analysis plan · Apr 12, 2022
Informed consent form · Jul 12, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Undecided

Registry details

Key details

Study ID: NCT03416153
Lead sponsor: University of Michigan Rogel Cancer Center
Collaborators: VA Ann Arbor Healthcare System, National Cancer Institute (NCI)
Responsible party: Sponsor
First posted: Jan 30, 2018
Start date: May 21, 2018
Primary completion: May 5, 2023
Completion: May 5, 2025
Results posted: May 22, 2025
Last update: Aug 7, 2026

Study contacts

Michelle Mierzwa, M.D.

principal investigator · University of Michigan Rogel Cancer Center

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: Yes

View the source record on ClinicalTrials.gov ↗

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