Induction Chemotherapy With Afatinib, Ribavirin, and Weekly Carboplatin/Paclitaxel for Stage IVA/IVB HPV Associated Oropharynx Squamous Cell Cancer (OPSCC)
Phase I Study of Induction Chemotherapy With Afatinib, Ribavirin, and Weekly Carboplatin/Paclitaxel for Stage IVA/IVB HPV Associated Oropharynx Squamous Cell Cancer (OPSCC)
調査の概要
研究の種類
入学 (実際)
段階
- フェーズ 1
連絡先と場所
研究場所
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New Jersey
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Basking Ridge、New Jersey、アメリカ、07939
- Memorial Sloan Kettering Cancer Center at Basking Ridge
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New York
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New York、New York、アメリカ、10065
- Memorial Sloan Kettering Cancer Center
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:なし
- 介入モデル:単一グループの割り当て
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的: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.
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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.
他の名前:
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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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maximum tolerated dose (For Dose Escalation Portion of the study)
時間枠:1 year
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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.
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1 year
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expression of PTPN13 (For Expansion Cohort only)
時間枠:1 year
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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.
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1 year
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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safety and tolerability (toxicity)
時間枠:1 year
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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.
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1 year
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objective response rate
時間枠:1 year
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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.
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1 year
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pharmacokinetics
時間枠:1 year
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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.
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1 year
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協力者と研究者
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- 12-150
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