Phase I Study of Induction Chemotherapy With Afatinib, Ribavirin, and Weekly Carboplatin/Paclitaxel for Stage IVA/IVB HPV Associated Oropharynx Squamous Cell Cancer (OPSCC)
- Department of Pathology at MSKCC confirmation of diagnosis of oropharynx squamous
cell cancer, stage IVA/IVB, that is HPV associated.
Evidence of HPV can be p16 immunohistochemistry and/or HPV in situ hybridization positive
test result on tumor tissue, either at MSKCC or other CLIA-approved lab.
- Age ≥ 18 years of age
- Karnofsky Performance Status ≥ 80
- Adequate organ function, as follows:
Adequate bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.5 X 109/L, platelets ≥
160 X 109/L, hemoglobin ≥ 12 g/dL Hepatic: total bilirubin within normal limits (≤ 1.0
mg/dL); alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase
(ALT) ≤ 1.5 X ULN (upper limit of normal) Renal: Serum creatinine ≤ 1.3 mg/dL. Patients
with serum creatinine > 1.3 mg/dL may be eligible if creatinine clearance (CrCl) ≥ 55
mL/min based on the standard Cockroft and Gault formula.
- Patients of childbearing potential must have a negative serum pregnancy test within
14 days of treatment. Patients must agree to use a reliable method of birth control
during and for 6 months following the last dose of study drug.
- Ability to swallow oral medication.
- Expansion Cohort only: At least one unstained slide from pre-treatment diagnostic
biopsy or fine needle aspirate must be available for correlative immunohistochemistry
- Prior chemotherapy or radiation for tonsillar or base of tongue squamous cell cancer
- History of hemolytic anemia or thalassemia
- Active infection or serious underlying medical condition that would impair the
patient's ability to receive protocol treatment.
- Current therapeutic anticoagulation with Coumadin (warfarin)
- Current or prior treatment with ribavirin
- Known active Hepatitis B or C
- Any prior documented history of transient ischemic attack (TIA) or cerebrovascular
- New York Heart Association (NYHA) Grade II or greater congestive heart failure
- Clinically significant peripheral vascular disease
- Inability to discontinue any of the following potent P-gp inhibitors (cyclosporine,
erythromycin, ketoconazole, itraconazole, quinidine, phenobarbital salt with
quinidine, ritonavir, valspodar, verapamil) or inducers (St John's wort, rifampicin).
- Known pre-existing interstitial lung disease.
- Presence of poorly controlled gastrointestinal disorders that could affect the
absorption of the trial drug (e.g. Crohn's disease, ulcerative colitis,
malabsorption, or CTC grade ≥2 diarrhea of any etiology) based on treating physician