VNP40101M in Treating Young Patients With Recurrent, Progressive, or Refractory Primary Brain Tumors
Phase I Study Of Cloretazine (VNP40101M) In Children With Recurrent, Progressive Or Refractory Primary Brain Tumors
RATIONALE: Drugs used in chemotherapy, such as VNP40101M, work in different ways to stop tumor cells from dividing so they stop growing or die.
PURPOSE: This phase I trial is studying the side effects and best dose of VNP40101M in treating young patients with recurrent, progressive, or refractory primary brain tumors.
調査の概要
詳細な説明
OBJECTIVES:
Primary
- Determine the maximum tolerated dose and dose-limiting toxicity of VNP40101M in pediatric patients with recurrent, progressive, or refractory primary brain tumors.
Secondary
- Determine the pharmacokinetics of this drug and its active metabolite VNP4090CE in these patients.
- Determine the efficacy of this drug in these patients.
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to receiving ≥ 1 of the following prior therapies: craniospinal irradiation (yes vs no), autologous bone marrow transplant (yes vs no), and > 2 myelosuppressive chemotherapy or myelosuppressive biologic therapy regimens (yes vs no).
Patients receive VNP40101M IV over 30 minutes on days 1-5. Treatment repeats every 42 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 2-6 patients per stratum receive escalating doses of VNP40101M until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 25% of patients experience dose-limiting toxicity. A total of 12 patients are treated at the MTD.
Patients are followed for 3 months.
PROJECTED ACCRUAL: A total of 4-60 patients (2-30 per stratum) will be accrued for this study within 18 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
-
-
California
-
San Francisco、California、アメリカ、94115
- UCSF Comprehensive Cancer Center
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-
District of Columbia
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Washington、District of Columbia、アメリカ、20010-2970
- Children's National Medical Center
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-
Illinois
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Chicago、Illinois、アメリカ、60614
- Children's Memorial Hospital - Chicago
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Massachusetts
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Boston、Massachusetts、アメリカ、02115
- Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
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North Carolina
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Durham、North Carolina、アメリカ、27710
- Duke Comprehensive Cancer Center
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Pennsylvania
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Philadelphia、Pennsylvania、アメリカ、19104-4318
- Children's Hospital of Philadelphia
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Pittsburgh、Pennsylvania、アメリカ、15213
- Children's Hospital of Pittsburgh
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Tennessee
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Memphis、Tennessee、アメリカ、38105
- St. Jude Children's Research Hospital
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Texas
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Houston、Texas、アメリカ、77030-2399
- Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
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Washington
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Seattle、Washington、アメリカ、98105
- Children's Hospital and Regional Medical Center - Seattle
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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
DISEASE CHARACTERISTICS:
Histologically confirmed* primary brain tumor, including benign brain tumors (e.g., low-grade glioma)
- Recurrent or progressive disease OR refractory to standard therapy NOTE: *Patients with intrinsic brain stem or diffuse optic pathway tumors do not require histological confirmation, but must have clinical and/or radiographic evidence of disease progression
- No bone marrow disease
PATIENT CHARACTERISTICS:
Age
- 21 and under
Performance status
- Karnofsky 50-100% (for patients > 16 years of age) OR
- Lansky 50-100% (for patients ≤ 16 years of age)
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count ≥ 1,000/mm^3*
- Platelet count ≥ 100,000/mm^3*
- Hemoglobin ≥ 8 g/dL* NOTE: *Unsupported
Hepatic
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- ALT and AST ≤ 2.5 times ULN
- No overt hepatic disease
Renal
- BUN < 25 mg/dL
- Creatinine ≤ 1.5 times ULN for age OR
- Glomerular filtration rate > 70 mL/min
- No overt renal disease
Cardiovascular
- Shortening fraction ≥ 30% by echocardiogram OR
- Ejection fraction ≥ 50% by gated radionucleotide study
- No clinically significant cardiac arrhythmia by EKG
- No overt cardiac disease
Pulmonary
- DLCO ≥ 60% of predicted
- Chest X-ray normal (defined as absence of pulmonary infiltrates, pneumonitis, pleural effusion, pulmonary hemorrhage, or fibrosis) AND a resting pulse oximetry reading of > 94% in room air (for patients who cannot perform the DLCO)
- No overt pulmonary disease
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Neurologic deficits allowed provided there has been no deficit progression for ≥ 1 week before study entry
- No uncontrolled infection
- No known hypersensitivity to polyethylene glycol
PRIOR CONCURRENT THERAPY:
Biologic therapy
- At least 6 months since prior allogeneic bone marrow or stem cell transplantation
- At least 3 months since prior autologous bone marrow or stem cell transplantation
- More than 1 week since prior colony-stimulating factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or epoetin alfa)
- At least 3 weeks since prior myelosuppressive anticancer biologic therapy
- No concurrent routine colony-stimulating factors
Chemotherapy
- At least 3 weeks since prior myelosuppressive anticancer chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
Endocrine therapy
- Concurrent corticosteroids allowed provided dose is stable or decreasing for ≥ 1 week before study entry
Radiotherapy
- At least 3 months since prior craniospinal irradiation ≥ 18 Gy
- At least 2 weeks since prior focal irradiation to the primary tumor and/or symptomatic metastatic sites
Surgery
- Not specified
Other
- At least 7 days since prior nonmyelosuppressive anticancer therapy
- At least 7 days since prior investigational agents
- Concurrent enzyme-inducing anticonvulsant drugs allowed
- No other concurrent anticancer or experimental agents or therapies
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）
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 |
時間枠 |
|---|---|
|
Estimate the maximum tolerated dose
時間枠：First 6 weeks of therapy
|
First 6 weeks of therapy
|
|
Number of participants with dose limiting toxicities
時間枠：First 6 weeks of therapy
|
First 6 weeks of therapy
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Pharmacokinetics
時間枠：Day 1 of therapy
|
Plasma samples for pharmacokinetic studies will be collected with the first dose of the study drug pre-infusion, and 5, 15, and 30 minutes, 1 hour, 2 hours, and 4 hours after the end of infusion.
VNP40101M plasma concentration-time data will be modeled and the individual pharmacokinetic pararmeters volume of the central compartment, elimination rate constant, and half-life will be estimated.
|
Day 1 of therapy
|
|
Tumor response to VNP40101M
時間枠：Prior to course 3, 5, and 7 and end of therapy
|
MRI of the brain will be obtained prior to couses 3, 5, and 7 and at the end of therapy
|
Prior to course 3, 5, and 7 and end of therapy
|
協力者と研究者
捜査官
- スタディチェア：Sri Gururangan, MRCP (UK)、Duke University
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
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 (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
キーワード
その他の研究ID番号
- CDR0000396779
- PBTC-017
- VION-VNP40101M
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