Head and Neck Cancer, Squamous Cell Carcinoma of the Head and Neck
Conditions
Keywords
oropharyngeal
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.
Interventions
DRUGIbrutinib 560mg PO daily (Imbruvica)
BTK inhibitor combined with PD-1 inhibitor
DRUGCetuximab
Cetuximab 400mg/m2 x 1 then 250 mg/m2 weekly 28 day cycle
DRUGNivolumab
Nivolumab 3mg/kg biweekly 28 day cycle
Sponsors
University of California, San Diego
Pharmacyclics LLC.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention 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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\- To be enrolled in the study, each potential subject must satisfy all of the following inclusion criteria. 1. 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. 2. Known p16 and/or HPV status by institutional standard. 3. Presence of measurable tumor lesions per RECIST criteria v1.1 by investigator review 4. Life expectancy greater than 12 weeks 5. Previously archived or newly obtained tumor specimens for correlative analysis 6. 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. 7. 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) 8. PT/INR \<1.5 x ULN and PTT (aPTT) \<1.5 x ULN 9. Men and women ≥ 18 years of age. 10. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 11. 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. 12. 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
Exclusion criteria
\- To be enrolled in the study, potential subjects must meet NONE of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Efficacy of Combined Therapies Using RECIST v1.1 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | Up to 30 months | Progression-free survival (PFS), defined as the interval from the date of first dose of ibrutinib to disease progression or death from any cause |
| Overall Survival | Up to 30 months | Overall survival (OS), defined as the date of first dose of ibrutinib to the date of death from any cause. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORKathryn Gold, MD
University of California San Diego, Moores Cancer Center
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 58 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Human Papillomavirus (HPV) Status Negative | 1 Participants |
| Human Papillomavirus (HPV) Status Positive | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 3 | 2 / 2 |
| other Total, other adverse events | 3 / 3 | 2 / 2 |
| serious Total, serious adverse events | 0 / 3 | 0 / 2 |
Outcome results
None listed