Trial of Ibrutinib Combined With Nivolumab or Cetuximab to Treat Recurrent/Metastatic HNSCC

NCT03646461 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 161755
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Head and Neck Cancer; Squamous Cell Carcinoma of the Head and Neck

Keywords

oropharyngeal

Outcome Measures

Primary Outcomes (1)

• 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

  3 yrs

Secondary Outcomes (4)

• Progression Free Survival

  3 yrs

• Overall Survival

  3 yrs

• Duration of Response

  3 yrs

• Safety as assessed by the frequency of adverse events per CTCAE v4.0

  3 yrs

Other Outcomes (1)

• Measurement of Biomarkers

  3 yrs

Study Arms (2)

Arm A: Ibrutinib + Cetuximab

EXPERIMENTAL

Ibrutinib 560mg PO daily (Imbruvica) PLUS Cetuximab 400mg/m2 x 1 then 250 mg/m2 weekly 28 day cycle

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

Drug: Ibrutinib 560mg PO daily (Imbruvica); Drug: Nivolumab

Interventions

Ibrutinib 560mg PO daily (Imbruvica) DRUG

BTK inhibitor combined with PD-1 inhibitor

Also known as: Imbruvica

Arm A: Ibrutinib + Cetuximab; Arm B: Ibrutinib + Nivolumab

Cetuximab DRUG

Cetuximab 400mg/m2 x 1 then 250 mg/m2 weekly 28 day cycle

Also known as: Erbitux

Arm A: Ibrutinib + Cetuximab

Nivolumab DRUG

Nivolumab 3mg/kg biweekly 28 day cycle

Also known as: opdivo

Arm B: Ibrutinib + Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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.
• 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.

Sponsors & Collaborators

• University of California, San Diego: lead
• Pharmacyclics LLC.: collaborator

Study Sites (1)

UCSD Moores Cancer Center

La Jolla, California, 92093, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

ibrutinib; Cetuximab; Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Kathryn Gold, MD

  University of California San Diego, Moores Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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

Study Record Dates

• First Submitted: June 8, 2018
• First Posted: August 24, 2018
• Study Start: October 17, 2018
• Primary Completion: December 11, 2025
• Study Completion: December 30, 2025
• Last Updated: April 6, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)