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

NCT01721525 | Completed Phase 1

• 1 other identifier: 12-150
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

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

Outcome Measures

Primary Outcomes (2)

• maximum tolerated dose (For Dose Escalation Portion of the study)

  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.

  1 year

• expression of PTPN13 (For Expansion Cohort only)

  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.

  1 year

Secondary Outcomes (3)

• safety and tolerability (toxicity)

  1 year

• objective response rate

  1 year

• pharmacokinetics

  1 year

Study Arms (1)

afatinib, ribavirin, and weekly carboplatin/paclitaxel

EXPERIMENTAL

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

Interventions

Afatinib, Ribavirin, and weekly carboplatin/paclitaxel 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.

Also known as: 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.

afatinib, ribavirin, and weekly carboplatin/paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Comprehensive Cancer Network: collaborator
• Boehringer Ingelheim: collaborator

Study Sites (2)

Memorial Sloan Kettering Cancer Center at Basking Ridge

Basking Ridge, New Jersey, 07939, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Head and Neck Neoplasms; Neoplasms, Squamous Cell

Interventions

Afatinib; Ribavirin; Paclitaxel; Jogging

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Running; Locomotion; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise; Motor Activity

Study Officials

• David Pfister, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2012
• First Posted: November 5, 2012
• Study Start: November 1, 2012
• Primary Completion: October 16, 2017
• Study Completion: October 16, 2017
• Last Updated: October 25, 2017

Record last verified: 2017-10

Locations

US (2)