A Phase 1 interventional study of Afatinib, Ribavirin, and weekly carboplatin/paclitaxel in Head and Neck Cancer and Squamous Cell Cancer, sponsored by Memorial Sloan Kettering Cancer Center. Completed at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-10-25.
Sponsored by Memorial Sloan Kettering Cancer Center · Phase 1, Interventional, and Treatment
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.
134 studies on the registry are indexed under Neoplasms, Squamous Cell; 14 are open to participants now.
This study's enrollment of 10 is below the median of 43 across 113 interventional studies indexed under Neoplasms, Squamous Cell.
Browse Neoplasms, Squamous Cell studies →Memorial Sloan Kettering Cancer Center is the lead sponsor of 1,930 studies on the registry; 328 are open to participants now.
Of its 129 completed or terminated interventional studies of FDA-regulated products, 66 (51%) have results posted.
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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.
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.
Exclusion Criteria:
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.
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.
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.
Time frame: 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.
Time frame: 1 year
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.
Time frame: 1 year
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.
Time frame: 1 year
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.
Time frame: 1 year
This study is completed, as verified in Oct 2017. You cannot join it, but the record below documents what was studied.
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Memorial Sloan Kettering Cancer Center