A Phase I-II Study of R115777 (Tipifarnib, Zarnestra®) Plus Sequential Weekly Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide in Patients With Stage IIB-IIIC Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 7
- 主要终点
- Number of Participants Analyzed for Phase II Dose of Tipifarnib When Combined With Weekly Sequential Paclitaxel (Phase I)
研究概览
简要总结
Tipifarnib may stop the growth of breast cancer by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as paclitaxel, doxorubicin, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving tipifarnib together with combination chemotherapy may kill more tumor cells. This phase I/II trial is studying the side effects and best dose of tipifarnib when given together with combination chemotherapy and to see how well they work in treating patients with stage II or stage III breast cancer.
详细描述
PRIMARY OBJECTIVES:
I. To determine the recommended phase II dose of tipifarnib when given together with paclitaxel in patients with stage IIB-IIIC breast cancer. (Phase I) II. To determine the pathologic complete remission rate (including breast and breast plus axillary nodes) in patients treated with sequential paclitaxel and tipifarnib followed by dose-dense doxorubicin hydrochloride, cyclophosphamide, and tipifarnib. (Phase II) III. To determine the feasibility and safety of this regimen in these patients. (Phase I and II)
OUTLINE: This is a multicenter, phase I, dose-escalation study of tipifarnib followed by a phase II study.
PHASE I: Paclitaxel plus tipifarnib: Patients receive paclitaxel IV over 1 hour on day 1 and oral tipifarnib twice daily on days 1-3.
Treatment repeats weekly for 12 courses in the absence of disease progression or unacceptable toxicity. Patients with no evidence of disease progression after 12 courses proceed to AC chemotherapy plus tipifarnib. Cohorts of 3-6 patients receive escalating doses of tipifarnib until the recommended phase II dose (RTPD) is determined. The RTPD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed adenocarcinoma of the breast; clinical stage IIB, IIIA, IIIB, or IIIC disease
- •At least 1 week since prior tamoxifen or other selective estrogen receptor modulator for prevention or for other indications (e.g., osteoporosis or prior ductal carcinoma in situ)
- •HER-2/neu-negative by immunohistochemistry or fluorescence in situ hybridization (FISH)
- •Hormone receptor status:
- •Estrogen and/or progesterone receptor-positive* [Note: *Patients enrolled on the phase I portion of the trial may have estrogen and progesterone receptor-negative disease]
- •Normal organ function including:
- •WBC >= 3,000/mm^3
- •Absolute neutrophil count >= 1,500/mm^3
- •Platelet count >= 100,000/mm^3
- •Bilirubin normal
- •AST and ALT =< 2.5 times upper limit of normal
- •LVEF normal by echocardiogram or nuclear scan
- •Creatinine normal OR Creatinine clearance >= 60 mL/min
- •FEV1 >= 1 L* and DLCO >= 50%* [Note: *Only if baseline CT scan of chest shows parenchymal lung disease OR there is a history of chronic obstructive or other pulmonary disease]
- •No prior chemotherapy, radiotherapy, or definitive therapeutic surgery (e.g., mastectomy, lumpectomy, or axillary dissection) for this cancer but prior sentinel lymph node biopsy for this malignancy allowed
- •No prior adjuvant chemotherapy for a previous breast malignancy
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •No other concurrent investigational agents
- •No other concurrent anticancer agents or therapies
- •ECOG performance status 0-1
- •Fertile patients must use effective contraception
- •Exclusion criteria:
- •No other invasive malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
- •No history of allergic reactions attributed to compounds of similar chemical or biological composition to tipifarnib or other study drugs (e.g., imidazoles or quinolones)
- •No other uncontrolled illness including, but not limited to, any of the following: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would preclude study compliance
- •Not pregnant or nursing
排除标准
- 未提供
研究组 & 干预措施
Arm I
Tipifarnib plus sequential weekly paclitaxel followed by doxorubicin plus cyclophosphamide
干预措施: tipifarnib (Drug)
Arm I
Tipifarnib plus sequential weekly paclitaxel followed by doxorubicin plus cyclophosphamide
干预措施: paclitaxel (Drug)
Arm I
Tipifarnib plus sequential weekly paclitaxel followed by doxorubicin plus cyclophosphamide
干预措施: doxorubicin (Drug)
Arm I
Tipifarnib plus sequential weekly paclitaxel followed by doxorubicin plus cyclophosphamide
干预措施: cyclophosphamide (Drug)
结局指标
主要结局
Number of Participants Analyzed for Phase II Dose of Tipifarnib When Combined With Weekly Sequential Paclitaxel (Phase I)
时间窗: 1 year
The recommended phase II dose of tipifarnib (100 or 200 mg PO BID on days 1-3 each paclitaxel dose) in combination with paclitaxel (80 mg/m2/week x 12 consecutive weeks)
Pathologic Complete Response Rate (pCR)
时间窗: Up to 5 years
An increase in the breast pCR from 15% (anticipated for chemotherapy alone) to 35% would be considered promising.
次要结局
未报告次要终点