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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborators:
National Comprehensive Cancer Network
Boehringer Ingelheim
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01721525
First received: November 1, 2012
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Squamous Cell Cancer
Drug: Afatinib, Ribavirin, and weekly carboplatin/paclitaxel
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Induction Chemotherapy With Afatinib, Ribavirin, and Weekly Carboplatin/Paclitaxel for Stage IVA/IVB HPV Associated Oropharynx Squamous Cell Cancer (OPSCC)

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • maximum tolerated dose (For Dose Escalation Portion of the study) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    of daily oral afatinib administered with standard daily weight based ribavirin and intravenous carboplatin and paclitaxel, 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.

  • expression of PTPN13 (For Expansion Cohort only) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    To determine if a two week run-in with afatinib and ribavirin results in increased expression of PTPN13, as determined by IHC in pre and post treatment biopsies.


Secondary Outcome Measures:
  • safety and tolerability (toxicity) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Adverse events (AEs) will be assessed according to NCI common toxicity criteria (CTC) version 4.0. Dose Limiting Toxicity (DLT) include all toxicities of grade 3 or higher felt to be possibly, probably, or definitely related to study drug.

  • objective response rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Response and progression will be evaluated in this study using modified international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) (51). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria.

  • pharmacokinetics [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    PK measurements will be collected from patients in the dose excalation cohort during the first cycle of therapy. The area under the curve (AUC0→∞), half-life (t½), and maximum concentration (Cmax) for afatinib will be determined by noncompartmental analysis.


Estimated Enrollment: 22
Study Start Date: November 2012
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: 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.
Other 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01721525

Contacts
Contact: Matthew Fury, MD PhD 646-888-4233
Contact: David Pfister, MD 646-888-4232

Locations
United States, New Jersey
Memorial Sloan-Kettering Cancer Center at Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07939
Contact: Matthew Fury, MD, PhD    646-888-4233      
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Matthew Fury, MD, PhD    646-888-4233      
Contact: David Pfiser, MD    646-888-4232      
Principal Investigator: Matthew Fury, MD, PhD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
National Comprehensive Cancer Network
Boehringer Ingelheim
Investigators
Principal Investigator: Matthew Fury, MD, PhD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01721525     History of Changes
Other Study ID Numbers: 12-150
Study First Received: November 1, 2012
Last Updated: May 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
BIBW2992 (AFATINIB)
CARBOPLATIN
RIBAVIRIN-ICN (VIRAZOLE)
TAXOL (PACLITAXEL)
OROPHARYNX
HPV associated
12-150

Additional relevant MeSH terms:
Head and Neck Neoplasms
Carcinoma, Squamous Cell
Neoplasms, Squamous Cell
Neoplasms by Site
Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Paclitaxel
Carboplatin
Ribavirin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on October 02, 2014