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

NCT ID: NCT01721525

Last Updated: 2017-10-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2017-10-16

Brief Summary

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.

Conditions

Head and Neck Cancer; Squamous Cell Cancer

Keywords

BIBW2992 (AFATINIB); CARBOPLATIN; RIBAVIRIN-ICN (VIRAZOLE); TAXOL (PACLITAXEL); OROPHARYNX; HPV associated; 12-150

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

afatinib, ribavirin, and weekly carboplatin/paclitaxel

This 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.

Group Type: EXPERIMENTAL

Afatinib, Ribavirin, and weekly carboplatin/paclitaxel

Intervention Type: DRUG

Patients 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.

Interventions

Afatinib, Ribavirin, and weekly carboplatin/paclitaxel

Patients 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.

Intervention Type: DRUG

Other Intervention Names

During the Expansion Cohort (Part 2), there is a two week run in of afatinib +; ribavirin. The Expansion Cohort begins with a Run-In period of approximately; 14 days, in which patients receive only afatinib + ribavirin. On Day -14; (Start of the of the Run-In), patients begin afatinib once daily (at 40 mg/daily the dose; established in Part 1) and ribavirin twice daily according to standard; weight-based dosing. Both afatinib and ribavirin are self-administered each; day during the Run-In period.

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Comprehensive Cancer Network

NETWORK

Sponsor Role: collaborator

Boehringer Ingelheim

INDUSTRY

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Pfister, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan Kettering Cancer Center at Basking Ridge

Basking Ridge, New Jersey, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Countries

United States

Related Links

http://www.mskcc.org/

Memorial Sloan Kettering Cancer Center

Other Identifiers

12-150

Identifier Type: -

Identifier Source: org_study_id