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
Overview
- Phase
- Phase 2
- Intervention
- Ibrutinib 560mg PO daily (Imbruvica)
- Conditions
- Head and Neck Cancer
- Sponsor
- University of California, San Diego
- Enrollment
- 5
- Locations
- 1
- Primary Endpoint
- Clinical Efficacy of Combined Therapies using RECIST v1.1
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
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
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.
Investigators
Kathryn Gold
Principal Investigator
University of California, San Diego
Eligibility Criteria
Inclusion Criteria
- •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
- •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.
Exclusion Criteria
- •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
- •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.
Arms & Interventions
Arm A: Ibrutinib + Cetuximab
Ibrutinib 560mg PO daily (Imbruvica) PLUS Cetuximab 400mg/m2 x 1 then 250 mg/m2 weekly 28 day cycle
Intervention: Ibrutinib 560mg PO daily (Imbruvica)
Arm A: Ibrutinib + Cetuximab
Ibrutinib 560mg PO daily (Imbruvica) PLUS Cetuximab 400mg/m2 x 1 then 250 mg/m2 weekly 28 day cycle
Intervention: Cetuximab
Arm B: Ibrutinib + Nivolumab
Ibrutinib 560mg PO daily (Imbruvica) PLUS Nivolumab 3mg/kg biweekly 28 day cycle
Intervention: Ibrutinib 560mg PO daily (Imbruvica)
Arm B: Ibrutinib + Nivolumab
Ibrutinib 560mg PO daily (Imbruvica) PLUS Nivolumab 3mg/kg biweekly 28 day cycle
Intervention: Nivolumab
Outcomes
Primary Outcomes
Clinical Efficacy of Combined Therapies using RECIST v1.1
Time Frame: 3 yrs
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
Secondary Outcomes
- Duration of Response(3 yrs)
- Progression Free Survival(3 yrs)
- Overall Survival(3 yrs)
- Safety as assessed by the frequency of adverse events per CTCAE v4.0(3 yrs)