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Head and Neck Cancer | Induction Chemotherapy With Afatinib, Ribavirin, and Weekly Carboplatin/Paclitaxel for Stage IVA/IVB HPV Associated Oropharynx Squamous Cell Cancer (OPSCC)

Head and Neck Cancer research study

What is the primary objective of this study?

This study seeks to develop a new induction chemotherapy regimen which is a combination of two pill drugs taken by mouth and two drugs given by vein. This is a phase I study, which means that the primary goal is to establish the recommended dose of an investigational drug when added to chemotherapy. The researchers wish to evaluate the effects, good and bad, of the investigational drug.

Who is eligible to participate?

Inclusion Criteria: - 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 study. Exclusion Criteria: - 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 accident (CVA) - 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 assessment.

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Head and Neck Cancer

Squamous Cell Cancer

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:Afatinib, Ribavirin, and weekly carboplatin/paclitaxelPatients will receive oral daily afatinib (days 1 - 21, per dose escalation scheme) plus daily oral ribavirin (days 1- 21) and paclitaxel (80 mg/m2 intravenously, days 1 and 8) + carboplatin (AUC 1.5 intravenously, days 1 and 8) of a 21-day cycle. Ribavirin will be administered according to standard weight-based dosing for this drug (1). Subjects ≤75 kg receive Ribavirin 400 mg PO qAM and 600 mg PO qPM (= 1000 mg/day). Subjects > 75 kg receive Ribavirin 600 mg PO BID (=1200 mg/day). During the Dose Escalation portion of the study (Part 1), research bloodwork for pharmacokinetics is performed on days 1 and 8 of Cycle 1 only.

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

afatinib, ribavirin, and weekly carboplatin/paclitaxelThis will be a single institution phase I study with an expansion cohort. Up to 2 dose levels of daily afatinib will be studied: 30 mg/day and 40 mg/day. The doses of ribavirin, carboplatin, and paclitaxel are fixed. A standard 3 + 3 phase I dose escalation design will be used.

Study Status

Completed

Start Date: November 2012

Completed Date: October 16, 2017

Phase: Phase 1

Type: Interventional

Design:

Primary Outcome: maximum tolerated dose (For Dose Escalation Portion of the study)

Secondary Outcome: safety and tolerability (toxicity)

Study sponsors, principal investigator, and references

Principal Investigator: David Pfister, MD

Lead Sponsor: Memorial Sloan Kettering Cancer Center

Collaborator: National Comprehensive Cancer Network

More information:https://clinicaltrials.gov/show/NCT01721525

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