Vorinostat and Alvocidib in Treating Patients With Advanced Solid Tumors
A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Flavopiridol in Advanced Solid Tumors
연구 개요
상세 설명
OBJECTIVES:
I. Determine the maximum tolerated dose of vorinostat (SAHA) when given in combination with flavopiridol (alvocidib) in patients with advanced solid tumors.
II. Obtain preliminary data on the therapeutic activity of SAHA and flavopiridol in these patients.
III. Evaluate the role of p21, p53, and apoptotic markers relative to treatment response in patients treated with this regimen.
OUTLINE: This is a multicenter, open label, non-randomized, dose-escalation study of vorinostat (SAHA).
Before beginning course 1 of study therapy, patients receive oral SAHA on days 1-3 in order to ensure tolerability of the drug. Beginning 1 week later, patients receive oral SAHA once daily on days 1-3 and 8-10 and fixed-dose alvocidib intravenously (IV) over 1 hour on days 2 and 9. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of SAHA 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. An additional 10 patients are treated at the MTD of SAHA in combination with fixed-dose alvocidib. Once the MTD of SAHA in combination with fixed-dose alvocidib is determined, patients receive oral SAHA at one dose level below the MTD once daily on days 1-3 and 8-10 and divided-dose alvocidib IV over 30 minutes followed by alvocidib IV over 4 hours on days 2 and 9. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. If this schedule is well-tolerated, the MTD of SAHA in combination with divided-dose flavopiridol is determined as above. An additional 10 patients are treated at the MTD of SAHA in combination with divided-dose alvocidib. Patients undergo blood draws on days 1 and 9 of course 1 for pharmacokinetic analysis.
After completion of study treatment, patients are followed for 4 weeks.
연구 유형
등록 (실제)
단계
- 1단계
연락처 및 위치
연구 장소
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New York
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New York, New York, 미국, 10065
- Memorial Sloan-Kettering Cancer Center
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
Histologically confirmed solid tumor
- Metastatic or unresectable disease
- Standard curative or palliative measures do not exist or are no longer effective
- No hematologic malignancies
- No known brain metastases
- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- WBC ≥ 3,000/mm^3
- Absolute 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
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs
No uncontrolled intercurrent illness, including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situations that would preclude study compliance
- Recovered from prior therapy
- At least 2 weeks since prior histone acetylase inhibitors, including valproic acid
- At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- At least 2 weeks since prior investigational therapy
- At least 2 weeks since prior radiotherapy
- No concurrent combination antiretroviral therapy for HIV-positive patients
No concurrent commonly used vitamins, antioxidants, or herbal preparations and supplements
- A single tablet multivitamin is allowed
- No other concurrent anticancer agents or therapies for this mailgnancy
- No other concurrent investigational agents
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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실험적: Treatment (chemotherapy, enzyme inhibitor)
Before beginning course 1 of study therapy, patients receive oral SAHA on days 1-3 in order to ensure tolerability of the drug.
Beginning 1 week later, patients receive oral SAHA once daily on days 1-3 and 8-10 and fixed-dose alvocidib IV over 1 hour on days 2 and 9. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
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주어진 IV
다른 이름들:
상관 연구
다른 이름들:
구두로 주어진
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Maximum tolerated dose of vorinostat when administered in combination with a fixed dose of weekly flavopiridol
기간: Course 1
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Defined as the dose one level below the dose at which two or more of the patients in the initial cohort experience dose limiting toxicities (DLT) during the first treatment course.
Graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 Term.
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Course 1
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Clinical pharmacokinetics of vorinostat (SAHA)
기간: Week 1 of course 1
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Week 1 of course 1
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Therapeutic activity of SAHA and flavopiridol
기간: Not Provided
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Not Provided
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Expression of p21, p53, and apoptotic markers relative to treatment response
기간: Baseline to 2 weeks after completion of study treatment
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Evaluated using immunohistochemistry.
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Baseline to 2 weeks after completion of study treatment
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공동 작업자 및 조사자
수사관
- 수석 연구원: Gary Schwartz, Memorial Sloan Kettering Cancer Center
연구 기록 날짜
연구 주요 날짜
연구 시작
기본 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
추가 관련 MeSH 약관
기타 연구 ID 번호
- NCI-2009-00090 (레지스트리 식별자: CTRP (Clinical Trial Reporting Program))
- U01CA069856 (미국 NIH 보조금/계약)
- P30CA008748 (미국 NIH 보조금/계약)
- 6858 (기타 식별자: CTEP)
- 05-109 (기타 식별자: Memorial Sloan-Kettering Cancer Center)
- MSKCC-05109
- CDR0000472411
- NCI-6858
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알보시딥에 대한 임상 시험
-
National Cancer Institute (NCI)종료됨