A Phase I-II Study of R115777 (ZARNESTRA) Plus Doxorubicin and Cyclophosphamide in Patients With Locally Advanced Breast Cancer and Metastatic Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- Pathological complete response in the breast
研究概览
简要总结
Drugs used in chemotherapy, such as doxorubicin and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Combining tipifarnib with doxorubicin and cyclophosphamide may kill more tumor cells. Phase II trial to study the effectiveness of combining tipifarnib with doxorubicin and cyclophosphamide in treating women who have locally advanced breast cancer.
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of tipifarnib when administered with doxorubicin and cyclophosphamide in women with metastatic breast cancer (non-regional stage IV disease). (Phase I closed to accrual as of 1/19/04) II. Determine the pathologic complete remission rate in patients with locally advanced breast cancer (stages IIB, IIIA, IIIB, or IIIC) treated with the recommended phase II dose of this regimen.
SECONDARY OBJECTIVES:
I. Determine the clinical complete response rate in patients treated with this regimen.
II. Determine the toxicity profile of this regimen in these patients. III. Correlate pretreatment levels of ErbB1, 2, 3, 4 and phosphorylated levels of Akt, STAT3, and Erk ½ with clinical response in these patients and with percent inhibition of proliferation (Ki-67) and percent induction of apoptosis in post-treatment tumor specimens.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed adenocarcinoma of the breast
- •Phase I (closed to accrual as of 1/19/04):
- •Nonregional stage IV disease
- •Phase II:
- •Locally advanced disease, according to AJCC staging criteria:
- •Stage IIB
- •Stage IIIA
- •Stage IIIB
- •Stage IIIC
- •At least 1 bidimensionally or unidimensionally measurable indicator lesion
- •Hormone receptor status:
- •Not specified
- •Performance status - ECOG 0-1
- •Performance status - Karnofsky 70-100%
- •Not specified
- •WBC at least 3,000/mm^3
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •Bilirubin normal
- •AST/ALT no greater than 2.5 times upper limit of normal
- •Creatinine normal
- •Creatinine clearance at least 60 mL/min
- •LVEF normal
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •No other invasive malignancies within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
- •No prior allergic reactions attributed to compounds of similar chemical or biological composition to tipifarnib or other agents used in the study (e.g., imidazoles or quinolones)
- •No ongoing or active infection
- •No other concurrent uncontrolled illness that would preclude study participation
- •No psychiatric illness or social situation that would preclude study compliance
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Not specified
- •Phase I (closed to accrual as of 1/19/04):
- •More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- •No more than 1 prior adjuvant/neoadjuvant regimen and 1 prior regimen for metastatic disease
- •Prior doxorubicin allowed provided the following are true:
- •Used in adjuvant setting
- •Cumulative dose was no greater than 240 mg/m^2
- •At least 1 year between completion of adjuvant therapy and relapse
- •Phase II:
- •No prior chemotherapy for locally advanced breast cancer
- •At least 1 week since prior tamoxifen or other selective estrogen receptor modulators for prevention or other indications (e.g., osteoporosis, ductal carcinoma in situ, or invasive breast cancer)
- •Phase I (closed to accrual as of 1/19/04):
- •More than 4 weeks since prior radiotherapy
- •Phase II:
- •No prior radiotherapy for locally advanced breast cancer
- •Not specified
- 另有 4 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (doxorubicin, cyclophosphamide, tipifarnib, G-CSF)
PHASE I (nonregional stage IV disease) (closed to accrual as of 1/19/04): Patients receive doxorubicin IV over 10-15 minutes and cyclophosphamide IV over 30 minutes on day 1, oral tipifarnib twice daily on days 2-7, and G-CSF subcutaneously on days 2-13. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
PHASE II (stage IIB, IIIA, IIIB, or IIIC): Patients receive tipifarnib at the MTD and doxorubicin, cyclophosphamide, and G-CSF as in phase I (phase I closed to accrual as of 1/19/04). After the fourth course, patients may undergo complete resection.
干预措施: doxorubicin hydrochloride (Drug)
Treatment (doxorubicin, cyclophosphamide, tipifarnib, G-CSF)
PHASE I (nonregional stage IV disease) (closed to accrual as of 1/19/04): Patients receive doxorubicin IV over 10-15 minutes and cyclophosphamide IV over 30 minutes on day 1, oral tipifarnib twice daily on days 2-7, and G-CSF subcutaneously on days 2-13. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
PHASE II (stage IIB, IIIA, IIIB, or IIIC): Patients receive tipifarnib at the MTD and doxorubicin, cyclophosphamide, and G-CSF as in phase I (phase I closed to accrual as of 1/19/04). After the fourth course, patients may undergo complete resection.
干预措施: cyclophosphamide (Drug)
Treatment (doxorubicin, cyclophosphamide, tipifarnib, G-CSF)
PHASE I (nonregional stage IV disease) (closed to accrual as of 1/19/04): Patients receive doxorubicin IV over 10-15 minutes and cyclophosphamide IV over 30 minutes on day 1, oral tipifarnib twice daily on days 2-7, and G-CSF subcutaneously on days 2-13. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
PHASE II (stage IIB, IIIA, IIIB, or IIIC): Patients receive tipifarnib at the MTD and doxorubicin, cyclophosphamide, and G-CSF as in phase I (phase I closed to accrual as of 1/19/04). After the fourth course, patients may undergo complete resection.
干预措施: tipifarnib (Drug)
Treatment (doxorubicin, cyclophosphamide, tipifarnib, G-CSF)
PHASE I (nonregional stage IV disease) (closed to accrual as of 1/19/04): Patients receive doxorubicin IV over 10-15 minutes and cyclophosphamide IV over 30 minutes on day 1, oral tipifarnib twice daily on days 2-7, and G-CSF subcutaneously on days 2-13. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
PHASE II (stage IIB, IIIA, IIIB, or IIIC): Patients receive tipifarnib at the MTD and doxorubicin, cyclophosphamide, and G-CSF as in phase I (phase I closed to accrual as of 1/19/04). After the fourth course, patients may undergo complete resection.
干预措施: filgrastim (Biological)
Treatment (doxorubicin, cyclophosphamide, tipifarnib, G-CSF)
PHASE I (nonregional stage IV disease) (closed to accrual as of 1/19/04): Patients receive doxorubicin IV over 10-15 minutes and cyclophosphamide IV over 30 minutes on day 1, oral tipifarnib twice daily on days 2-7, and G-CSF subcutaneously on days 2-13. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
PHASE II (stage IIB, IIIA, IIIB, or IIIC): Patients receive tipifarnib at the MTD and doxorubicin, cyclophosphamide, and G-CSF as in phase I (phase I closed to accrual as of 1/19/04). After the fourth course, patients may undergo complete resection.
干预措施: therapeutic conventional surgery (Procedure)
Treatment (doxorubicin, cyclophosphamide, tipifarnib, G-CSF)
PHASE I (nonregional stage IV disease) (closed to accrual as of 1/19/04): Patients receive doxorubicin IV over 10-15 minutes and cyclophosphamide IV over 30 minutes on day 1, oral tipifarnib twice daily on days 2-7, and G-CSF subcutaneously on days 2-13. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
PHASE II (stage IIB, IIIA, IIIB, or IIIC): Patients receive tipifarnib at the MTD and doxorubicin, cyclophosphamide, and G-CSF as in phase I (phase I closed to accrual as of 1/19/04). After the fourth course, patients may undergo complete resection.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Pathological complete response in the breast
时间窗: 8 weeks
95% confidence intervals of these estimates will be obtained.
次要结局
- Proportion of patients who have a clinical complete response(8 weeks)
- Grade 3 or 4 toxicities assessed using NCI CTCAE version 3.0(Up to 5 years)
- Median disease-free survival(Up to 5 years)
- Percentage of patients free of disease(2 years)