Induction Chemotherapy With Afatinib, Ribavirin, and Weekly Carboplatin/Paclitaxel for Stage IVA/IVB HPV Associated Oropharynx Squamous Cell Cancer (OPSCC)
|ClinicalTrials.gov Identifier: NCT01721525|
Recruitment Status : Completed
First Posted : November 5, 2012
Last Update Posted : October 25, 2017
|Condition or disease||Intervention/treatment||Phase|
|Head and Neck Cancer Squamous Cell Cancer||Drug: Afatinib, Ribavirin, and weekly carboplatin/paclitaxel||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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)|
|Actual Study Start Date :||November 2012|
|Actual Primary Completion Date :||October 16, 2017|
|Actual Study Completion Date :||October 16, 2017|
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.
- maximum tolerated dose (For Dose Escalation Portion of the study) [ Time Frame: 1 year ]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 ]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.
- safety and tolerability (toxicity) [ Time Frame: 1 year ]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 ]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 ]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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01721525
|United States, New Jersey|
|Memorial Sloan Kettering Cancer Center at Basking Ridge|
|Basking Ridge, New Jersey, United States, 07939|
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||David Pfister, MD||Memorial Sloan Kettering Cancer Center|