7-hydroxystaurosporine and Cisplatin in Treating Patients With Advanced Malignant Solid Tumors
Phase I Dose Escalation Study of UCN-01 (NSC 638850) Plus Cisplatin in Advanced Malignant Solid Tumors
調査の概要
詳細な説明
OBJECTIVES:
I. To establish the maximum tolerated dose (MTD) of cisplatin in combination with UCN-01 in patients with advanced malignancies.
II. To assess the toxicity and observe the potential antitumor activity of UCN-01 plus cisplatin in advanced malignancies at each dose level studies.
III. To determine the pharmacokinetics of UCN-01 and cisplatin on this treatment schedule.
IV. To perform laboratory correlative studies to investigate intermediate molecular markers of the activity of UCN-01 and cisplatin at the cellular level.
OUTLINE: This is a dose-escalation study of cisplatin.
Patients receive cisplatin IV over 1 hour on day 1 and UCN-01 IV continuously over 36-72 hours on day 2. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of cisplatin 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.
Patients are followed every 2-3 months for at least 1 year.
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 Hampshire
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Lebanon、New Hampshire、アメリカ、03756
- Dartmouth Hitchcock Medical 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:
- Advanced or metastatic, histologcally/cytologically confirmed malignant solid tumor, not expected to clinically benefit from standard therapy
- Life expectancy greater than 3 months
- Previous chemotherapy and/or radiotherapy must have been completed at least four weeks (six weeks for prior treatment with mitomycin or nitrosoureas) and patients should have recovered from all toxicities of that therapy before treatment under this protocol
- All patients must have recovered from any surgical procedure
- Serum creatinine must be within the institutional limits of normal and an estimated creatinine clearance of >= 60 ml/min
- Normal bilirubin is required
- SGOT/AST must be less than or equal to 2.5 times the upper limit of institutional normal
- WBC >= 4000/mm^3
- Absolute neutrophil count >= 2000/mm^3
- Platelet count >= 150,000/mm^3
- Patients must have a Karnofsky Performance Status of 60% or greater
- Subjects who are fertile must use a medically acceptable contraceptive throughout the treatment period and for three months following cessation of treatment; subjects must be made aware, before entering this trial, of the risk in becoming pregnant or in fathering children
- A signed informed consent (approved by the IRB) must be obtained prior to trial entry
- Tumor site accessible for both pre-treatment and post-treatment biopsy is preferred during dose-finding, and is required for patients entering the expanded cohort at the MTD
- All patients require a central indwelling venous catheter prior to treatment under this protocol
Exclusion Criteria:
- Peripheral neuropathy > grade I
- Any prior mediastinal radiotherapy
- Any history of coronary artery disease
- Class III or IV congestive heart failure according to the New York Heart Classification
- History of allergic reactions to appropriate diuretics or antiemetics (e.g., 5-HT3 antagonists) to be administered in conjunction with protocol directed chemotherapy
- Brain metastasis
- Uncontrolled intercurrent illness that would preclude tolerance and completion of the protocol treatment, including vigorous hydration prior and subsequent to cisplatin therapy
- Lactating or pregnant women are excluded to avoid potential harm to the unborn child or infant; documentation of a negative, serum beta-HCG pregnancy test must be available for pre-menopausal women with intact reproductive organs and for women less than two years after menopause
- Receipt of any investigational drug within 30 days before beginning treatment with study drug
- Medical, social, or psychological factors that would prevent the patient from completing the treatment protocol
- Patients with clinically significant hearing loss
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:Treatment (7-hydroxystaurosporine, cisplatin)
Patients receive cisplatin IV over 1 hour on day 1 and UCN-01 IV continuously over 36-72 hours on day 2. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
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相関研究
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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MTD of cisplatin defined as the highest dose level in which six patients have been evaluated for toxicity with no more than one patient experiencing DLT attributable to the study drugs
時間枠:4 weeks
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Graded using the NCI CTCAE.
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4 weeks
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Toxicity observed at each dose level, graded using the NCI CTCAE
時間枠:Up to 7 years
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Summarized in terms of type, severity, time of onset, duration, and reversibility or outcome.
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Up to 7 years
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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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Objective tumor response
時間枠:Up to 7 years
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Summarized at each dose level, and the number and percent responding combined across dose levels.
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Up to 7 years
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Overall survival
時間枠:From registration to time of death due to any cause, assessed up to 7 years
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Summarized with Kaplan-Meier plots.
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From registration to time of death due to any cause, assessed up to 7 years
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Time to treatment failure
時間枠:From registration to the first observation of disease progression, death due to any cause, or early discontinuation of treatment, assessed up to 7 years
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Summarized with Kaplan-Meier plots.
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From registration to the first observation of disease progression, death due to any cause, or early discontinuation of treatment, assessed up to 7 years
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Duration of response
時間枠:Up to 7 years
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Summarized with Kaplan-Meier plots.
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Up to 7 years
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協力者と研究者
捜査官
- 主任研究者:Raymond Perez、Dartmouth-Hitchcock Medical 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-2012-03129
- DMS 9934
- DMS-9934
- NCI-2331
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