A Phase 2 interventional study of Nivolumab and Ipilumimab in Cutaneous Squamous Cell Carcinoma (CSCC), Cutaneous Squamous Cell Cancer and Cutaneous Squamous Cell Carcinoma of the Head and Neck, sponsored by The Netherlands Cancer Institute. Recruiting at 5 sites in Netherlands. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-05-29.
Sponsored by The Netherlands Cancer Institute · Phase 2, Interventional, and Treatment
The goal of this clinical trial is to determine whether cutaneous squamous cell carcinoma patients can be cured using only immunotherapy, without surgery or radiotherapy.
This is an investigator-initiated phase 2 clinical trial consisting of 41 patients with stage I-IVa CSCC and an indication for morbid/extensive curative surgery. All patients will receive two courses of nivolumab 3 mg/kg in week 0 and week 2, and one course of ipilimumab 1 mg/kg in week 0. In week 5 response to immunotherapy will be evaluated using clinical examination, [18F]FDG-PET/CT imaging, regional lymph node ultrasound with FNAC (if applicable) and a multicentre multidisciplinary meeting. Non-responders will receive standard of care surgery (w/wo radiotherapy). Responders will enter a wait-and-monitor follow-up schedule in which response will be monitored every 3 months for a total of 2 years. If a patient is no longer responding to immunotherapy during follow-up they will receive standard of care surgery (w/wo radiotherapy).
2,018 studies on the registry are indexed under Squamous Cell Carcinoma of Head and Neck; 573 are open to participants now.
This study's planned enrollment of 41 is below the median of 48 across 1,653 interventional studies indexed under Squamous Cell Carcinoma of Head and Neck.
Browse Squamous Cell Carcinoma of Head and Neck studies →The Netherlands Cancer Institute is the lead sponsor of 231 studies on the registry; 67 are open to participants now.
Compared within Squamous Cell Carcinoma of Head and Neck, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Neoplasms, Squamous Cell. The counts are of registry records indexed under each term, refreshed daily. How we classify →
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.
Exclusion Criteria:
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Intravenous neoadjuvant nivolumab 3 mg/kg in week 0 and 2 in combination with intravenous neoadjuvant ipilimumab 1 m/kg in week 0.
Drug: Nivolumab · Drug: Ipilumimab
3 mg/kg
Also known as: Immunotherapy
1 mg/kg
Also known as: Immunotherapy
This study also gives Ipilimumab. No intervention listed here names it: that was found by reading the record.
Rate of clinical complete remission after only immunotherapy
The rate of patients with a clinical complete remission at 24 months of follow-up or at time of death prior to 24 months follow-up, whichever comes first, after only immunotherapy, without surgery, radiotherapy or maintenance immunotherapy.
Time frame: From the start of immunotherapy until 24 months of follow-up
Rate of clinical complete remission after only immunotherapy
The rate of patients with a clinical complete remission at 12 and 18 months of follow-up or at time of death prior to the specified time-point, whichever comes first, after only immunotherapy, without surgery, radiotherapy or maintenance immunotherapy
Time frame: From the start of immunotherapy until 12 and 18 months of follow-up.
Immune-related adverse events
The rate and type of immune-related adverse events (CTCAE v5.0, Clavien-Dindo).
Time frame: From the start of immunotherapy until 100 days after the last course of immunotherapy.
Health-related quality of life (EORTC QLQ-C30)
EORTC Core Quality of Life questionnaire. Rated on a Likert-type scale from one (never) to four (almost always), to evaluate different domains. Functional and global health status scales indicated towards better levels of functioning, whereas higher scores in the symptom scales demonstrated higher levels of symptoms.
Time frame: From the start of immunotherapy until 24 months of follow-up.
Health-related quality of life (EORTC QLQ-H&N35)
EORTC Head and Neck Cancer Quality of Life Questionnaire. Rated on a Likert-type scale from one (never) to four (almost always). Multi-item scales (pain, swallowing, senses, speech, social eating, social contact, and sexuality), and six symptom items (dental problems, opening mouth, dry mouth, sticky saliva, coughing, and feeling ill). Higher scores in the symptom scales demonstrated higher levels of symptoms.
Time frame: From the start of immunotherapy until 24 months of follow-up.
Health-related quality of life (EQ5D)
EuroQol Five Dimensions Health Questionnaire. Domains: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. It also includes a VAS regarding patients' "Health Today" scored between 0 and 100. Each domain will be converted into categorical values (problems vs no problems).
Time frame: From the start of immunotherapy until 24 months of follow-up.
Health-related quality of life (CWS)
Cancer worry scale. Rated on a Likert-type scale from one (never) to four (almost always), which were summed to produce a total CWS score ranging from 8 to 32, with higher scores indicating more frequent worries about cancer.
Time frame: From the start of immunotherapy until 24 months of follow-up.
Health-related quality of life (IT)
Immunotherapy questionnaire. Rated on a Likert-type scale from one (never) to four (almost always), to evaluate toxicity after immunotherapy treatment.
Time frame: From the start of immunotherapy until 24 months of follow-up.
Health-related quality of life (sexuality questionnaire)
Rated on a Likert-type scale from one (never) to four (almost always), to evaluate problems in sexual functioning.
Time frame: From the start of immunotherapy until 24 months of follow-up.
Treatment duration
Total duration of received treatment
Time frame: From the start of immunotherapy until the end of treatment (average 6 weeks)
Treatment stops
The amount of times and the length of time the immunotherapy, surgery or adjuvant radiotherapy had to be stopped.
Time frame: From the start of immunotherapy until the end of treatment (average 6 weeks)
Disease-specific survival
The length of time a patient survives without death due to disease.
Time frame: From the start of immunotherapy until 2 years follow-up.
Recurrence-free survival
The length of time a patient survives without recurrent disease.
Time frame: From the start of immunotherapy until 2 years follow-up.
Event-free survival
The length of time a patient survives without recurrent disease or death of any cause.
Time frame: From the start of immunotherapy until 2 years follow-up.
Overall survival
The length of time a patient survives after treatment.
Time frame: From the start of immunotherapy until 2 years follow-up.
Healthcare consumption
Healthcare consumption during the trial.
Time frame: From the start of immunotherapy until 24 months of follow-up.
Cost-effectiveness
The incremental cost-effectiveness ratio between quality-adjusted life years and the cost of trial-related healthcare.
Time frame: From the start of immunotherapy until 24 months of follow-up.
Tumor micro-environment (IHC)
Temporal and spatial analyses of the TME in the lymph nodes and primary tumours will be explored using immunohistochemistry (e.g. PD-L1 expression, CPS score).
Time frame: From enrollment until week 5
Tumor micro-environment (RNAseq)
Temporal and spatial analyses of the TME in the lymph nodes and primary tumours will be explored using bulk and single-cell RNA-sequencing.
Time frame: From enrollment until week 5
Tumor micro-environment (spatial mass cytometry)
Temporal and spatial analyses of the TME in the lymph nodes and primary tumours will be explored using spatial mass cytometry.
Time frame: From enrollment until week 5
Immune dynamics (PBMC)
Temporal immune dynamics in peripheral blood will be investigated via peripheral blood mononuclear cells (PBMCs).
Time frame: From enrollment until week 5
Immune dynamics (TCR)
Temporal immune dynamics in peripheral blood will be investigated via TCR analyses of peripheral immune cells in comparison to intratumoural immune cells
Time frame: From enrollment until week 5
ctDNA
The ctDNA in peripheral blood using CyclomicsSeq
Time frame: From enrollment until week 5.
Complement activation
Complement activation, complement mediated neutrophil activation in the TME and their contribution on the immune response during neoadjuvant immunotherapy
Time frame: From enrollment until week 5
Humoural immunity
Activation of humoral immunity, and specifically treatment-induced changes in antibody production and their relation with treatment response
Time frame: From enrollment until week 5
Plan to share: Yes
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Studies of the drugs tested here: Nivolumab · Ipilimumab
Squamous Cell Carcinoma of Head and Neck →
The Netherlands Cancer Institute →