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.
연구 개요
상세 설명
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.
연구 유형
등록 (실제)
단계
- 1단계
연락처 및 위치
연구 장소
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California
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San Francisco, California, 미국, 94115
- UCSF Comprehensive Cancer Center
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District of Columbia
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Washington, District of Columbia, 미국, 20010-2970
- Children's National Medical Center
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Illinois
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Chicago, Illinois, 미국, 60614
- Children's Memorial Hospital - Chicago
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Massachusetts
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Boston, Massachusetts, 미국, 02115
- Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
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North Carolina
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Durham, North Carolina, 미국, 27710
- Duke Comprehensive Cancer Center
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Pennsylvania
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Philadelphia, Pennsylvania, 미국, 19104-4318
- Children's Hospital of Philadelphia
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Pittsburgh, Pennsylvania, 미국, 15213
- Children's Hospital of Pittsburgh
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Tennessee
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Memphis, Tennessee, 미국, 38105
- St. Jude Children's Research Hospital
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Texas
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Houston, Texas, 미국, 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, 미국, 98105
- Children's Hospital and Regional Medical Center - Seattle
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
기간 |
|---|---|
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Estimate the maximum tolerated dose
기간: First 6 weeks of therapy
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First 6 weeks of therapy
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Number of participants with dose limiting toxicities
기간: First 6 weeks of therapy
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First 6 weeks of therapy
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Pharmacokinetics
기간: 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.
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Day 1 of therapy
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Tumor response to VNP40101M
기간: Prior to course 3, 5, and 7 and end of therapy
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MRI of the brain will be obtained prior to couses 3, 5, and 7 and at the end of therapy
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Prior to course 3, 5, and 7 and end of therapy
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공동 작업자 및 조사자
수사관
- 연구 의자: Sri Gururangan, MRCP (UK), Duke University
간행물 및 유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (추정)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
키워드
기타 연구 ID 번호
- CDR0000396779
- PBTC-017
- VION-VNP40101M
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