Ibrutinib and Cetuximab or Nivolumab in Treating Patients with Recurrent or Metastatic Head and Neck Squamous Cell Cancer
- 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 Response Evaluation Criteria in Solid Tumors (RECIST) criteria version (v)1.1 by investigator review
- Life expectancy greater than 12 weeks
- Previously archived or newly obtained tumor specimens for correlative analysis
- Absolute neutrophil count > 750 cells/mm^3 (0.75 x 10^9/L) (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)
- Platelet count > 50,000 cells/mm^3 (50 x 10^9/L) (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)
- Hemoglobin > 8.0 g/dL (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)
- 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 upper limit of normal (ULN) (unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin)
- Prothrombin time (PT)/international normalized ratio (INR) < 1.5 x ULN and partial thromboplastin time (PTT) (activated [a]PTT) < 1.5 x ULN
- 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 of reproductive potential who agree to use both 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 30 days after the last dose of study drug for females and 90 days for males; ability and willingness to provide written informed consent
- 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) 28 days prior to first administration of study treatment
- Prior exposure to BTK 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
- Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE v4.03), 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
- Subject who received a strong cytochrome P450 (CYP) 3A inhibitor within 7 days prior to the first dose of ibrutinib or subject who requires continuous treatment with a strong CYP3A inhibitor
- Subjects with chronic liver disease with hepatic impairment Child-Pugh class B or C according to the Child-Pugh Classification
- Female subjects who are pregnant, or breastfeeding, or planning to become pregnant while enrolled in this study or within 90 days of last dose of study drug; male subjects who plan to father a child while enrolled in this study or within 90 days after the last dose of study drug
- 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)
I. To determine the clinical efficacy of ibrutinib in combination with cetuximab or nivolumab in patients with recurrent (R)/metastatic (M) head and neck squamous cell carcinoma (HNSCC) as defined by overall response rate.
I. To determine overall frequency and severity of adverse events.
II. To determine progression-free survival.
III. To determine overall survival.
IV. To determine the duration of response of these two treatment regimens.
I. To prospectively collect blood and tumor tissue specimens to determine biomarkers of response to treatment with ibrutinib in combination with cetuximab or nivolumab.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive ibrutinib orally (PO) once daily (QD) on days -7 to -1 prior to cycle 1 and on days 1-28 of subsequent cycles. Patients also receive cetuximab intravenously (IV) over 60-120 minutes on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive ibrutinib PO QD on days -7 to -1 prior to cycle 1 and on days 1-28 of subsequent cycles. Patients also receive nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up within 28 days, every month for 1 year, and then every 2 months for up to 5 years.
Trial Phase Phase II
Trial Type Treatment
University of California San Diego
Kathryn Ann Gold
- Primary ID UCSD 161755
- Secondary IDs NCI-2017-01420
- Clinicaltrials.gov ID NCT03646461