Phase I Study of Induction Chemotherapy With Afatinib, Ribavirin, and Weekly Carboplatin/Paclitaxel for Stage IVA/IVB HPV Associated Oropharynx Squamous Cell Cancer (OPSCC)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- maximum tolerated dose (For Dose Escalation Portion of the study)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Afatinib, Ribavirin, and weekly carboplatin/paclitaxel (Drug)
结局指标
主要结局
maximum tolerated dose (For Dose Escalation Portion of the study)
时间窗: 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)
时间窗: 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.
次要结局
- safety and tolerability (toxicity)(1 year)
- objective response rate(1 year)
- pharmacokinetics(1 year)