Azacitidine and Recombinant Interferon Alfa-2b in Treating Patients With Stage III or Stage IV Melanoma or Stage IV Kidney Cancer That Cannot Be Removed By Surgery
A Phase 1 Study of 5-azacitidine in Combination With Interferon-Alfa 2B in Unresectable or Metastatic Melanoma and Renal Cell Carcinoma
調査の概要
状態
詳細な説明
OBJECTIVES:
I. Determine the adverse event profile and maximum tolerated dose of interferon alfa-2b when combined with azacitidine in patients with unresectable stage III or IV melanoma or unresectable stage IV renal cell carcinoma.
II. Determine the feasibility of this regimen for future phase II trials.
OUTLINE: This is a dose-escalation, multicenter study.
Patients receive azacitidine subcutaneously (SC) once daily on days 1-4 and 15-17 and recombinant interferon alfa-2b SC on days 8, 10, 12, 15, 17, 19, 22, 24, and 26 during course 1. Beginning in course 2 and for all subsequent courses, patients receive azacitidine SC once daily on days 1-3 and 15-17 and interferon alfa-2b SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 12 total courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of interferon alfa-2b until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. After completion of study treatment, patients are followed every 2-4 months.
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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Connecticut
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New Haven、Connecticut、アメリカ、06520-8032
- Yale University
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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:
Histologically confirmed diagnosis of 1 of the following:
Melanoma
- Unresectable stage III disease
- Stage IV disease
Renal cell carcinoma
- Unresectable and/or stage IV disease
- Measurable disease
No untreated brain metastases or leptomeningeal disease
- Patients with previously treated brain metastases are eligible provided they have no evidence of progression for ≥ 4 weeks following treatment and do not require steroids
- Performance status - ECOG 0-2
- Performance status - Karnofsky 60-100%
- More than 3 months
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 9.0 g/dL (may be transfused to this level)
- PT or PTT < 1.5 times upper limit of normal (ULN)
- Bilirubin ≤ 2.0 mg/mL
- AST and ALT ≤ 3 times ULN (5 times ULN for patients with liver metastases)
- Albumin ≥ 3.0 g/dL
- Creatinine ≤ 1.7 mg/dL
- Creatinine clearance ≥ 50 mL/min
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No ventricular cardiac arrhythmia
- No myocardial infarction within the past 3 months
- No dyspnea at rest
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No active gastrointestinal bleeding or ulcer disease
- No ongoing or active infection
- No psychiatric illness or social situation that would preclude study compliance
- No other uncontrolled illness
- No history of allergic reaction attributed to compounds of similar chemical or biologic composition to study agents
- At least 2 weeks since prior immunotherapy
- Prior adjuvant interferon alfa for metastatic disease or in the adjuvant setting allowed
- At least 3 weeks since prior cytotoxic agents (6 weeks for nitrosoureas or mitomycin)
- See Disease Characteristics
- At least 2 weeks since prior hormonal therapy
- At least 1 week since prior and no concurrent steroids
- At least 3 weeks since prior radiotherapy
- At least 2 weeks since prior minor surgery
- At least 3 weeks since prior major surgery
- Recovered from all prior therapy
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent investigational agents
- No other concurrent anticancer therapy
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 (chemotherapy, biological therapy)
Patients receive azacitidine SC once daily on days 1-4 and 15-17 and recombinant interferon alfa-2b SC on days 8, 10, 12, 15, 17, 19, 22, 24, and 26 during course 1. Beginning in course 2 and for all subsequent courses, patients receive azacitidine SC once daily on days 1-3 and 15-17 and interferon alfa-2b SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26.
Treatment repeats every 28 days for up to 12 total courses in the absence of disease progression or unacceptable toxicity.
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与えられた SC
他の名前:
Given SC
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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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Adverse event profile of azacitidine and recombinant interferon alfa-2b in patients with unresectable or metastatic melanoma and renal cell carcinoma
時間枠:Continuously throughout study
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Graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
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Continuously throughout study
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Maximum tolerated dose of recombinant interferon alfa-2b when administered in combination with 5-azacitidine
時間枠:Course 1 (4 weeks)
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Toxicity will be graded according to the NCI CTCAE version 3.0.
The MTD is the highest dose level in which < 2 patients of 6 develop first cycle DLT.
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Course 1 (4 weeks)
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Correlation of promoter methylation with the level of expression of the genes
時間枠:Day 5 or 8 and 24 or 26 of course 1
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Determined by Western blotting, immunohistochemistry, and/or RT-PCR.
We will use Western blot analysis when antibodies are available and semi-quantitative RT-PCR in cases where antibodies are not available.
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Day 5 or 8 and 24 or 26 of course 1
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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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Response rate of giving recombinant interferon alfa-2b when administered in combination with 5-azacitidine in patients with metastatic melanoma and renal cell carcinoma
時間枠:Every 8 weeks
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Evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.
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Every 8 weeks
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協力者と研究者
捜査官
- 主任研究者:Mario Sznol、Yale University
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-2009-00152
- YALE HIC#27409
- YALE-HIC-27409
- NCI-7317
- CDR0000441640
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