Head and Neck CancerPhase 2NCT03646461
Trial of Ibrutinib Combined With Nivolumab or Cetuximab to Treat Recurrent/Metastatic HNSCC
A Phase 2 study testing Ibrutinib 560mg PO daily (Imbruvica), Cetuximab and Nivolumab in people with Head and Neck Cancer and Squamous Cell Carcinoma of the Head and Neck, run by University of California, San Diego at 1 site in United States.
Trial summary
This is an open-label, randomized, phase II trial to test the efficacy of Ibrutinib in combination with either Nivolumab or Cetuximab in the treatment of recurrent and/or metastatic head an neck squamous cell carcinoma Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer, Squamous Cell Carcinoma of the Head and Neck
- What is being tested?
- Ibrutinib 560mg PO daily (Imbruvica), Cetuximab and Nivolumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Oct 2018to 13 May 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- To be enrolled in the study, each potential subject must satisfy all of the following inclusion criteria.
- Histologically or cytologically proven squamous cell carcinoma of the head and neck not amenable to curative intent therapy. P16 or HPV status must be known on all patients with oropharyngeal primaries or unknown primaries.
- Known p16 and/or HPV status by institutional standard.
- Presence of measurable tumor lesions per RECIST criteria v1.1 by investigator review
- Life expectancy greater than 12 weeks
- Previously archived or newly obtained tumor specimens for correlative analysis
Show all 19Show fewer
- Adequate hematologic function independent of transfusion and growth factor support for at least 7 days prior to screening and randomization, with the exception of pegylated G-CSF (pegfilgrastim) and darbepoetin which require at least 14 days prior to screening and randomization defined as:
- Absolute neutrophil count >750 cells/mm3 (0.75 x 109/L).
- Platelet count >50,000 cells/mm3 (50 x 109/L).
- Hemoglobin >8.0 g/dL.
- Adequate hepatic and renal function defined as:
- Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 3.0 x upper limit of normal (ULN).
- Estimated Creatinine Clearance ≥30 ml/min (Cockcroft-Gault)
- Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
- PT/INR <1.5 x ULN and PTT (aPTT) <1.5 x ULN
- Men and women ≥ 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- Female subjects who are of non-reproductive potential (ie, post-menopausal by history - no menses for ≥1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy). Female subjects of childbearing potential must have a negative serum pregnancy test upon study entry.
- Male and female subjects who agree to use highly effective methods of birth control (eg, , implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], complete abstinence, or sterilized partner) and a barrier method (eg., condoms, vaginal ring, sponge, etc) during the period of therapy and for for 30 days after the last dose of study drug for females and 90 days for males.Ability and willingness to provide written informed consent
Who cannot join
- To be enrolled in the study, potential subjects must meet NONE of the following exclusion criteria:
- Prior therapy with an EGFR inhibitor in the recurrent or metastatic setting
- Nasopharyngeal carcinoma histology
- Known, clinically active central nervous system metastases (stable metastases permitted)
- Chemotherapy ≤ 28 days prior to first administration of study treatment and/or monoclonal antibody (including immunotherapy) ≤16 weeks prior to first administration of study treatment.
- Prior exposure to BTK inhibitor, PD-1 inhibitor, or PD-L1 inhibitor
Show all 30Show fewer
- History of other malignancies, except:
- Malignancy treated with curative intent and with no known active disease present for ≥3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician.
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
- Adequately treated carcinoma in situ without evidence of disease.
- Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc., or chronic administration [>14 days] of >10 mg/day of prednisone) within 28 days of the first dose of study drug.
- Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
- Recent infection requiring systemic treatment that was completed ≤14 days before the first dose of study drug.
- Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE v4.0), Grade ≤1, or to the levels dictated in the inclusion/exclusion criteria with the exception of alopecia.
- Known bleeding disorders (eg, von Willebrand's disease) or hemophilia.
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
- Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus (HCV) or hepatitis B virus (HBV). Subjects who are positive for hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded.
- Any uncontrolled active systemic infection.
- Any history of interstitial lung disease.
- Active autoimmune disease or other contraindication to PD-1 inhibition.
- Major surgery within 4 weeks of first dose of study drug.
- Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk.
- Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization.
- Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.
- Concomitant use of warfarin or other Vitamin K antagonists.
- Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor
- Currently active, clinically significant hepatic impairment Child-Pugh Class B or C according to the Child-Pugh Classification
- Lactating or pregnant.
- Unwilling or unable to participate in all required study evaluations and procedures.
- Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations).
Trial locations and contacts
1 site in 1 country.
United States1 site
UCSD Moores Cancer Center
La Jolla, California, 92093
About this study
Official title: A Multi-Institutional, Open-Label, Randomized, Phase II Trial Of Ibrutinib In Combination With EGFR Inhibition Or PD-1 Inhibition In Patients With Recurrent/Metastatic Head And Neck Squamous Cell Carcinoma
This is an open-label, randomized, phase II trial to test the efficacy of Ibrutinib in combination with either Nivolumab or Cetuximab in the treatment of recurrent and/or metastatic head an neck squamous cell carcinoma
Read the detailed description
Open-label, randomized, controlled, clinical trial. Enrollment will be stratified by HPV status and randomized in a 1:1 ratio to either ibrutinib + cetuximab or ibrutinib + nivolumab
The study will enroll patients who develop R/M HNSCC have not yet been treated with EGFR inhibitors in the recurrent/metastatic setting. All patients being considered for the study must be ≥ 18 years of age and will receive: i) ibrutinib + cetuximab or ii) ibrutinib + nivolumab.
To determine the clinical efficacy of ibrutinib in combination with cetuximab or nivolumab in patients with R/M HNSCC.
Ibrutinib will be supplied by Pharmacyclics as 140 mg hard gelatin capsules for oral (PO) administration.
Cetuximab will be supplied as a clear, colorless liquid formulated for intravenous administration.
Nivolumab will be supplied as a clear, colorless liquid formulated for intravenous administration.
- Keywords
- oropharyngeal
- Medical subject headings
- Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ibrutinib 560mg PO daily (Imbruvica)Drug
Also called Imbruvica
BTK inhibitor combined with PD-1 inhibitor
CetuximabDrug
Also called Erbitux
Cetuximab 400mg/m2 x 1 then 250 mg/m2 weekly 28 day cycle
NivolumabDrug
Also called opdivo
Nivolumab 3mg/kg biweekly 28 day cycle
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Ibrutinib + Cetuximab | Experimental | Ibrutinib 560mg PO daily (Imbruvica) PLUS Cetuximab 400mg/m2 x 1 then 250 mg/m2 weekly 28 day cycle Receives: Drug: Ibrutinib 560mg PO daily (Imbruvica); Drug: Cetuximab |
| Arm B: Ibrutinib + Nivolumab | Experimental | Ibrutinib 560mg PO daily (Imbruvica) PLUS Nivolumab 3mg/kg biweekly 28 day cycle Receives: Drug: Ibrutinib 560mg PO daily (Imbruvica); Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Efficacy of Combined Therapies Using RECIST v1.1
The primary endpoint is the clinical efficacy of each combinatorial treatment regimen as defined by the best overall response rate (proportion of patients with a partial or complete response in tumor burden) using RECIST v1.1. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: Up to 22 months
Secondary outcomes (2)
Progression Free Survival
Progression-free survival (PFS), defined as the interval from the date of first dose of ibrutinib to disease progression or death from any cause
Measured: Up to 30 months
Overall Survival
Overall survival (OS), defined as the date of first dose of ibrutinib to the date of death from any cause.
Measured: Up to 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2018
- Study start17 Oct 2018
- Primary completion15 Aug 2020
- Study completion13 May 2021
Why it stopped: Lack of scientific process of cancer-related clinical intervention
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Open-label, multi-center, randomized, controlled, clinical trial. Enrollment will be stratified by HPV status and randomized in a 1:1 ratio to either ibrutinib + cetuximab or ibrutinib + nivolumab
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- Pharmacyclics LLC.
- Responsible party
- Principal investigator, Kathryn Gold, University of California, San Diego
- Investigators
- Kathryn Gold, MD, Principal investigator, University of California San Diego, Moores Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03646461
- Sponsor's protocol ID
- 161755
- Status last verified
- Apr 2026
- First submitted
- 8 Jun 2018
- Last updated
- 22 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Institutional, Open-Label, Randomized, Phase II Trial Of Ibrutinib In Combination With EGFR Inhibition Or PD-1 Inhibition In Patients With Recurrent/Metastatic Head And Neck Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT03646461
- Acronym / sponsor ID
- 161755
- Keywords
- oropharyngeal
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of scientific process of cancer-related clinical intervention
- Enrolment
- 5 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- Pharmacyclics LLC.
- Study start
- 17 Oct 2018 (actual)
- Primary completion
- 15 Aug 2020 (actual)
- Study completion
- 13 May 2021 (actual)
- First posted
- 24 Aug 2018 (actual)
- Results
- Posted 22 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, randomized, phase II trial to test the efficacy of Ibrutinib in combination with either Nivolumab or Cetuximab in the treatment of recurrent and/or metastatic head an neck squamous cell carcinoma
Detailed description
Open-label, randomized, controlled, clinical trial. Enrollment will be stratified by HPV status and randomized in a 1:1 ratio to either ibrutinib + cetuximab or ibrutinib + nivolumab
The study will enroll patients who develop R/M HNSCC have not yet been treated with EGFR inhibitors in the recurrent/metastatic setting. All patients being considered for the study must be ≥ 18 years of age and will receive: i) ibrutinib + cetuximab or ii) ibrutinib + nivolumab.
To determine the clinical efficacy of ibrutinib in combination with cetuximab or nivolumab in patients with R/M HNSCC.
Ibrutinib will be supplied by Pharmacyclics as 140 mg hard gelatin capsules for oral (PO) administration.
Cetuximab will be supplied as a clear, colorless liquid formulated for intravenous administration.
Nivolumab will be supplied as a clear, colorless liquid formulated for intravenous administration.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Open-label, multi-center, randomized, controlled, clinical trial. Enrollment will be stratified by HPV status and randomized in a 1:1 ratio to either ibrutinib + cetuximab or ibrutinib + nivolumab
| Arm | Type | Receives |
|---|---|---|
| Arm A: Ibrutinib + Cetuximab | Experimental | Drug: Ibrutinib 560mg PO daily (Imbruvica), Drug: CetuximabIbrutinib 560mg PO daily (Imbruvica) PLUS Cetuximab 400mg/m2 x 1 then 250 mg/m2 weekly 28 day cycle |
| Arm B: Ibrutinib + Nivolumab | Experimental | Drug: Ibrutinib 560mg PO daily (Imbruvica), Drug: NivolumabIbrutinib 560mg PO daily (Imbruvica) PLUS Nivolumab 3mg/kg biweekly 28 day cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- To be enrolled in the study, each potential subject must satisfy all of the following inclusion criteria.
- Histologically or cytologically proven squamous cell carcinoma of the head and neck not amenable to curative intent therapy. P16 or HPV status must be known on all patients with oropharyngeal primaries or unknown primaries.
- Known p16 and/or HPV status by institutional standard.
- Presence of measurable tumor lesions per RECIST criteria v1.1 by investigator review
- Life expectancy greater than 12 weeks
Key exclusion criteria (30 listed)
- To be enrolled in the study, potential subjects must meet NONE of the following exclusion criteria:
- Prior therapy with an EGFR inhibitor in the recurrent or metastatic setting
- Nasopharyngeal carcinoma histology
- Known, clinically active central nervous system metastases (stable metastases permitted)
- Chemotherapy ≤ 28 days prior to first administration of study treatment and/or monoclonal antibody (including immunotherapy) ≤16 weeks prior to first administration of study treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ibrutinib 560mg PO daily (Imbruvica)Also: ImbruvicaBTK inhibitor combined with PD-1 inhibitor | Drug | Arm A: Ibrutinib + Cetuximab, Arm B: Ibrutinib + Nivolumab |
| CetuximabAlso: ErbituxCetuximab 400mg/m2 x 1 then 250 mg/m2 weekly 28 day cycle | Drug | Arm A: Ibrutinib + Cetuximab |
| NivolumabAlso: opdivoNivolumab 3mg/kg biweekly 28 day cycle | Drug | Arm B: Ibrutinib + Nivolumab |
Primary outcome
Clinical Efficacy of Combined Therapies Using RECIST v1.1
Time frame: Up to 22 months
The primary endpoint is the clinical efficacy of each combinatorial treatment regimen as defined by the best overall response rate (proportion of patients with a partial or complete response in tumor burden) using RECIST v1.1. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
2 secondary outcomes
Progression Free Survival
Time frame: Up to 30 months
Overall Survival
Time frame: Up to 30 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kathryn Gold, MD principal investigator
University of California San Diego, Moores Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ibrutinib 560mg PO daily (Imbruvica), Cetuximab and Nivolumab in people with Head and Neck Cancer and Squamous Cell Carcinoma of the Head and Neck, run by University of California, San Diego at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Efficacy of Combined Therapies Using RECIST v1.1 (time frame: Up to 22 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.