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

Primary Purpose

Head and Neck Cancer, Squamous Cell Cancer

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Afatinib, Ribavirin, and weekly carboplatin/paclitaxel

About this trial

This is an interventional treatment trial for Head and Neck Cancer focused on measuring BIBW2992 (AFATINIB), CARBOPLATIN, RIBAVIRIN-ICN (VIRAZOLE), TAXOL (PACLITAXEL), OROPHARYNX, HPV associated, 12-150

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Memorial Sloan Kettering Cancer Center at Basking Ridge
Memorial Sloan Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

afatinib, ribavirin, and weekly carboplatin/paclitaxel

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

safety and tolerability (toxicity)

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

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

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.

Full Information

NCT ID

NCT01721525

First Posted

November 1, 2012

Last Updated

October 23, 2017

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Comprehensive Cancer Network, Boehringer Ingelheim

1. Study Identification

Unique Protocol Identification Number

NCT01721525

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

October 2017

Overall Recruitment Status

Completed

Study Start Date

November 2012 (Actual)

Primary Completion Date

October 16, 2017 (Actual)

Study Completion Date

October 16, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Comprehensive Cancer Network, Boehringer Ingelheim

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Head and Neck Cancer, Squamous Cell Cancer

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

afatinib, ribavirin, and weekly carboplatin/paclitaxel

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Afatinib, Ribavirin, and weekly carboplatin/paclitaxel

Other Intervention Name(s)

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.

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Description

Time Frame

1 year

Title

expression of PTPN13 (For Expansion Cohort only)

Description

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.

Time Frame

1 year

Secondary Outcome Measure Information:

Title

safety and tolerability (toxicity)

Description

Time Frame

1 year

Title

objective response rate

Description

Time Frame

1 year

Title

pharmacokinetics

Description

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David Pfister, MD

Organizational Affiliation

Memorial Sloan Kettering Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Memorial Sloan Kettering Cancer Center at Basking Ridge

City

Basking Ridge

State/Province

New Jersey

ZIP/Postal Code

07939

Country

United States

Facility Name

Memorial Sloan Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.mskcc.org/

Description

Memorial Sloan Kettering Cancer Center

Learn more about this trial

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

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