Alvocidib, Oxaliplatin, Fluorouracil, and Leucovorin Calcium in Treating Patients With Advanced Solid Tumors
An Open-Labeled, Non-Randomized Phase I Study of Alvocidib (Flavopiridol) Administered With Oxaliplatin and Fluorouracil/Leucovorin in Patients With Advanced Solid Tumors
調査の概要
詳細な説明
OBJECTIVES:
I. Determine the maximum tolerated dose of flavopiridol when given in combination with oxaliplatin, fluorouracil, and leucovorin calcium in patients with advanced solid tumors.
II. Determine the pharmacokinetics of this regimen in these patients. III. Determine, preliminarily, the therapeutic activity of this regimen in these patients.
IV. Determine the dose-limiting toxicity and the recommended phase II dose of flavopiridol when administered with this regimen in these patients.
V. Determine the safety and tolerability of this regimen in these patients. VI. Correlate p21, p53, and apoptotic markers with response in patients treated with this regimen.
OUTLINE: This is a non-randomized, open-label, dose-escalation study of flavopiridol.
Patients receive alvocidib intravenously (IV) over 1 hour, oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 48 hours on days 1, 15, and 29. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of alvocidib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, the cohort is expanded and an additional 10 patients are treated at that dose.
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 York
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New York、New York、アメリカ、10065
- Memorial Sloan-Kettering Cancer Center
-
-
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:
Histologically confirmed advanced solid tumor
- Refractory to standard therapy or no standard therapy exists
- Evaluable disease
No known untreated CNS metastases
- Patients who have undergone local treatment for brain metastases and whose brain metastases are stable by repeat imaging study performed ≤ 4 weeks after treatment are allowed
- No primary CNS tumors
- Performance status - Karnofsky 60-100%
- WBC ≥ 3,500/mm^3
- Neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Bilirubin ≤ 1.5 mg/dL
- AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN for liver metastases)
- Creatinine ≤ 1.5 mg/dL
- No cardiac arrhythmias within the past 6 months
- No congestive heart failure within the past 6 months
- No myocardial infarction within the past 6 months
- No arterial or venous thrombosis within the past year
- No peripheral neuropathy > grade 1
- No other medical condition that would preclude study participation
- No serious or uncontrolled infection
- HIV negative
Not pregnant or nursing
- No nursing during and for 2 months after study participation
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 2 months after study participation
- At least 2 weeks since prior immunotherapy
- At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin)
- No prior flavopiridol
- At least 2 weeks since prior radiotherapy
- Recovered from all prior therapy
No concurrent therapy for thrombosis
- Prophylaxis for central lines or deep vein thrombosis allowed
- No other concurrent investigational medications
No concurrent vitamins, antioxidants, or herbal preparations and supplements
- Concurrent single-tablet multivitamin allowed
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 |
|---|---|
|
実験的：Treatment (alvocidib with oxaliplatin, 5-FU, leucovorin)
Patients receive alvocidib IV over 1 hour, oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 48 hours on days 1, 15, and 29. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, the cohort is expanded and an additional 10 patients are treated at that dose. |
与えられた IV
他の名前：
与えられた IV
他の名前：
与えられた IV
他の名前：
与えられた IV
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 of biweekly alvocidib when given in conjunction with oxaliplatin, 5-fluorouracil, and leucovorin calcium
時間枠：6 weeks
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Defined as the dose level immediately preceding the dose where 2 or more patients experienced dose-limiting toxicity.
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6 weeks
|
二次結果の測定
結果測定 |
時間枠 |
|---|---|
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Dose-limiting toxicity as defined by the occurrence of Grade 4 hematologic toxicity, Grade 3 or 4 non-hematologic toxicity including diarrhea despite antidiarrheal prophylaxis, or any delay in treatment resulting in less than 3 treatments in 6 weeks
時間枠：6 weeks
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6 weeks
|
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Recommended phase II dose of alvocidib
時間枠：6 weeks
|
6 weeks
|
協力者と研究者
捜査官
- 主任研究者：Gary Schwartz、Memorial Sloan Kettering Cancer Center
研究記録日
主要日程の研究
研究開始
一次修了 (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 (見積もり)
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
追加の関連 MeSH 用語
その他の研究ID番号
- NCI-2009-00055 (レジストリ識別子：CTRP (Clinical Trial Reporting Program))
- U01CA069856 (米国 NIH グラント/契約)
- MSKCC-03146
- CDR0000357606
- NCI-6365
- 03-146A (その他の識別子：Memorial Sloan-Kettering Cancer Center)
- 6365 (その他の識別子：CTEP)
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