Phase I-II Study of Vorinostat, Paclitaxel, and Bevacizumab in Metastatic Breast Cancer
Phase I/II Study of a Combination of Suberoylanilide Hydroxamic Acid (Vorinostat) Plus Paclitaxel and Bevacizumab in Patients With Advanced Metastatic and/or Local Chest Wall Recurrent Breast Cancer
연구 개요
상세 설명
PRiMARY OBJECTIVES:
I. To determine the recommended phase II dose of oral suberoylanilide hydroxamic acid (vorinostat) in combination with weekly paclitaxel and bevacizumab in patients with chest wall recurrent or metastatic breast cancer. (Phase I) II. To determine the efficacy (response rate, response duration, time to disease progression, time to treatment failure, and overall survival) and toxicity of oral suberoylanilide hydroxamic acid (vorinostat) in combination with weekly paclitaxel and bevacizumab in patients with chest wall recurrent or metastatic breast cancer. (Phase II)
SECONDARY OBJECTIVES:
I. To determine whether in vivo treatment with vorinostat induces a) acetylation of proteins including histone H3 and H4, b) ubiquitylation of proteins, and c) the levels of p21 and p27 levels in the peripheral blood mononuclear cells (pre treatment vs. cycle 1 day 2 after 3 VORINOSTAT doses but prior to paclitaxel.
II. To determine whether in vivo treatment with vorinostat induces a) acetylation of proteins including histone H3 and H4, ubiquitylation of proteins, and c) the levels of Bim, Bak, tBID, p21 and p27 levels, as well as down regulate Bcl-2, Bcl-xL and survivin in chest wall recurrent or metastatic breast cancer cells (pre treatment vs. cycle 1 day 2 after 3 vorinostat doses but prior to paclitaxel).
III. To determine whether in the primary breast cancer (and metastatic cancer if available) pretreatment levels of Her-2, Estrogen Receptor (ER)-alpha, Progesterone Receptor (PR), p21, p27, p-AKT, p-ERK1/2, HDAC1, 2, 3, 4, 6, 10 and SIRT2 levels predict for the response to treatment with VORINOSTAT plus paclitaxel.
OUTLINE: This is a phase I, multicenter, dose-escalation study of vorinostat (SAHA) followed by a phase II, open-label study.
Phase I: Patients receive oral SAHA twice daily on days 1-3, 8-10, and 15-17, paclitaxel IV over 1 hour on days 2, 9, and 16, and bevacizumab IV over 30-90 minutes on days 2 and 16. Treatment repeats every 28 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 3 or 2 of 6 patients experience dose-limiting toxicity. The recommended phase II dose is defined as one dose level below the MTD.
Phase II: Patients receive SAHA at the recommended phase II dose and paclitaxel and bevacizumab as in phase I.
연구 유형
등록 (실제)
단계
- 2 단계
- 1단계
연락처 및 위치
연구 장소
-
-
New York
-
Bronx, New York, 미국, 10467-2490
- Montefiore Medical Center
-
-
참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- histologically or cytologically confirmed adenocarcinoma of the breast; effective with version 2.2 (1/26/09), only patients with disease that is accessible to biopsy and consent to serial biopsy are eligible
- stage IV disease, locally recurrent inoperable chest wall disease; at least one bidimensional and/or unidimensional, measurable indicator lesion must be present (patients with only non-measurable disease are eligible for the phase I trial only); all sites of disease should be noted and followed
- ECOG performance status =< 1 (Karnofsky >= 70%)
- Absolute neutrophil count >= 1,500/ul
- Platelets >= 100,000/ul
- Total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) =< 2.5 x institutional upper limit of normal
- PTT and either INR or PT < 1.5 x normal
- Creatinine within normal institutional limits OR creatinine clearance >= mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Urine protein should be screened by urine analysis for Urine Protein Creatinine (UPC) ratio; for UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg for patient enrollment;
- LVEF must be at or above the lower institutional limit of the normal range (on MUGA or Echo obtained within 12 weeks of registration, or within 4 weeks of prior Herceptin)
- Not pregnant/lactating
Exclusion criteria:
- chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
- may not be receiving any other investigational agents.
- history of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat or other agents used in the study (e.g., paclitaxel, bevacizumab, quinolones)
- uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
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 |
|---|---|
|
실험적: vorinostat, paclitaxel, bevacizumab
Vorinostat BID on days 1-3, 8-10, and 15-17, paclitaxel IV over 1 hour on days 2, 9, and 16, bevacizumab IV over 30-90 minutes on days 2 and 16, repeat every 28 days.
|
주어진 IV
다른 이름들:
주어진 IV
다른 이름들:
구두로 주어진
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Recommended Phase II Dose as Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Phase I)
기간: 28 days
|
Dose-limiting toxcities (DLT) were defined as grade 3-4 febrile neutropenia, thrombocytopenia and non-hemtological toxicity attributed to therapy (nausea, vomiting and diarrhea would be considered dose limiting only if not adequately controlled with therapy).
Any toxicity occurring during cycle 1 that resulted in dose reduction of vorinostat or paclitaxel or failure to complete all protocol specificed doses in the first cycle was also considered a DLT
|
28 days
|
|
Objective Response Rate (CR + PR)
기간: Up to 12 months
|
Estimated and a 95% confidence interval will be estimated via binomial proportions.
Per Response Evaluation Criteria in Solid Tumors (RECIST) for target lesions and assessed by CT scan: Complete response (CR): Disappearance of all target lesions; Partial Response (PR): >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR+PR.
|
Up to 12 months
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Progression-free Survival (PFS),
기간: From first treatment day until objective or symptomatic progression, assessed up to 12 months
|
Assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formulae.
|
From first treatment day until objective or symptomatic progression, assessed up to 12 months
|
|
Time to Treatment Failure (TTF)
기간: Time from the first treatment day until disease progression or discontinuation of treatment due to toxicity, assessed up to 12 months
|
Assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formulae.
Time to treatment failure was not reported for this study.
|
Time from the first treatment day until disease progression or discontinuation of treatment due to toxicity, assessed up to 12 months
|
|
Overall Survival(OS)
기간: Time from first treatment day until death, assessed up to 12 months
|
Assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formulae.
|
Time from first treatment day until death, assessed up to 12 months
|
공동 작업자 및 조사자
수사관
- 수석 연구원: Joseph Sparano, Montefiore Medical Center
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
추가 관련 MeSH 약관
기타 연구 ID 번호
- NCI-2012-03012 (레지스트리 식별자: CTRP (Clinical Trial Reporting Program))
- N01CM62204 (미국 NIH 보조금/계약)
- N01CM62207 (미국 NIH 보조금/계약)
- N01CM62205 (미국 NIH 보조금/계약)
- N01CM62209 (미국 NIH 보조금/계약)
- 7703 (CTEP)
- 06-05-291 (기타 식별자: Montefiore Medical Center)
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. .