PS-341 and Combination Chemotherapy in Treating Patients With Advanced Solid Tumors
A Phase I and Pharmacologic Study of the Proteasome Inhibitor PS-341 in Combination With Paclitaxel and Carboplatin in Patients With Advanced Malignancies
연구 개요
상세 설명
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of bortezomib and paclitaxel administered in combination with carboplatin in patients with advanced solid tumors.
II. Compare the tolerability and efficacy of the different sequences of this regimen in these patients.
III. Determine the clinical toxic effects and pharmacokinetics of this regimen in these patients.
IV. Determine, preliminarily, the therapeutic activity of this regimen in these patients.
V. Evaluate p53 accumulation as a marker of PS-341 activity, and the effect of paclitaxel/carboplatin on PS-341 induced accumulation of p53.
VI. Exam the effect of PS-341 on the levels of other proteasome targets, e.g. mdm2, p27, p21, cyclins B, D1,E; IκB and other ubiquitinated proteins in tumor tissue, when available.
OUTLINE: This is a dose-escalation study of bortezomib and paclitaxel. Patients are assigned to 1 of 2 treatment groups.
Group A: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and bortezomib IV over 3-5 seconds on days 2, 5, and 8.
Group B: Patients receive bortezomib IV over 3-5 seconds on days 1, 4, and 8 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 2.
Treatment in both groups repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. After 6 courses of paclitaxel and carboplatin, patients with stable or responding disease may continue with bortezomib alone at the discretion of the investigator. Cohorts of 3-6 patients in each group receive escalating doses of bortezomib and paclitaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.
Patients are followed at 3 months.
PROJECTED ACCRUAL: A total of 24-96 patients will be accrued for this study within 25 months.
연구 유형
등록 (실제)
단계
- 1단계
연락처 및 위치
연구 장소
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Minnesota
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Rochester, Minnesota, 미국, 55905
- Mayo Clinic
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- Histologically confirmed malignancy for which no known standard therapy that is potentially curative or definitely capable of extending life expectancy exists
- No hematologic malignancies
No symptomatic CNS metastases
- Brain metastases allowed if previously treated (radiotherapy and/or surgery)and patient is stable for at least 8 weeks
- Performance status - ECOG 0-2
- At least 12 weeks
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- AST no greater than 2.5 times ULN
- Creatinine no greater than 1.5 times ULN
- No New York Heart Association class III or IV heart disease
- HIV negative
- No peripheral neuropathy grade 2 or greater
- No uncontrolled infection
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- More than 4 weeks since prior biologic therapy
- More than 4 weeks since prior immunotherapy
- No prior bone marrow transplantation
- No concurrent immunotherapy
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- No other concurrent chemotherapy
- More than 4 weeks since prior radiotherapy
- No prior radiotherapy to more than 30% of bone marrow
- No concurrent radiotherapy
- No concurrent investigational ancillary therapy
- No concurrent enrollment in another study involving a pharmacologic agent (e.g., drugs, biologics, immunotherapy, or gene therapy) for symptom control or therapeutic intents
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위화되지 않음
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: Group I (paclitaxel, carboplatin, bortezomib)
Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and bortezomib IV over 3-5 seconds on days 2, 5, and 8.
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주어진 IV
다른 이름들:
주어진 IV
다른 이름들:
선택적 상관 연구
주어진 IV
다른 이름들:
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실험적: Group II (bortezomib, paclitaxel, carboplatin)
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, and 8 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 2
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주어진 IV
다른 이름들:
주어진 IV
다른 이름들:
선택적 상관 연구
주어진 IV
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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MTD of paclitaxel, bortezomib, and carboplatin defined as the highest safely-tolerated dose where =< 1 patient experience dose-limiting toxicity (DLT) with the next higher dose having at least 2 patients who experience DLT as assessed by CTC version 2.0
기간: 21 days
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21 days
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Number of toxicity incidents as assessed by CTC Version 2.0
기간: 21 days
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Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.
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21 days
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Number of responses
기간: Up to 3 months
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Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses.
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Up to 3 months
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Change in p53 accumulation
기간: From baseline to up to 3 months
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From baseline to up to 3 months
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Change in other proteasome levels
기간: From baseline to up to 3 months
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From baseline to up to 3 months
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공동 작업자 및 조사자
수사관
- 수석 연구원: Alex Adjei, Mayo Clinic
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 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
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