Phase Ib/II Neoadjuvant Trial of the Farnesyltransferase Inhibitor, R115777 With Docetaxel and Capecitabine for Patients With Stage IIIA or IIIB Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 53
- 试验地点
- 7
- 主要终点
- Dose-limiting toxicity (DLT) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 (Phase I)
研究概览
简要总结
Phase I/II trial to study the effectiveness of neoadjuvant tipifarnib combined with docetaxel and capecitabine in treating patients who have locally advanced or metastatic solid tumors or stage IIIA or stage IIIB breast cancer. Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy, such as docetaxel and capecitabine, use different ways to stop tumor cells from dividing so they stop growing or die. Combining tipifarnib with docetaxel and capecitabine may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose and recommended dose of capecitabine in combination with docetaxel and tipifarnib in patients with locally advanced or metastatic solid tumors. (Phase Ib) II. Determine the complete pathological and clinical response rate in patients with stage IIIA or IIIB breast cancer treated with this regimen. (Phase II)
SECONDARY OBJECTIVES:
I. Determine the toxicity of this regimen in these patients. II. Determine disease-free and overall survival of patients treated with this regimen.
OUTLINE: This is a multicenter, dose-escalation study of capecitabine. Patients in phase II are stratified according to type of breast cancer (inflammatory vs noninflammatory).
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 solid tumor
- •Locally advanced or metastatic
- •No known standard therapy that is potentially curative or definitely capable of extending life expectancy
- •No history of metastatic brain disease within the past 6 months
- •Treated metastatic brain disease is allowed provided disease has been stable for more than 6 months and does not require concurrent steroids or anti-seizure medication
- •Histologically confirmed breast cancer
- •Stage IIIA or stage IIIB, including ipsilateral palpable supraclavicular lymph node(s) without other distant metastasis
- •Invasive disease confirmed by 1 of the following*:
- •Incisional biopsy
- •Punch biopsy (applicable for clinical T4b tumors)
- •Core needle (cutting needle) biopsies
- •No distant metastatic disease
- •Hormone receptor status:
- •Not specified
- •Male or female
- •Performance status - ECOG 0-1
- •Absolute neutrophil count at least 2,000/mm^3
- •Platelet count at least 100,000/mm^3
- •Hemoglobin at least 10.0 g/dL
- •Bilirubin no greater than upper limit of normal (ULN)
- •Alkaline phosphatase no greater than 2.5 times ULN
- •AST no greater than 2.5 times ULN
- •Creatinine no greater than 1.25 times ULN
- •Creatinine clearance at least 50 mL/min
- •No cardiac arrhythmia
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No active infection requiring antibiotics
- •No diabetes
- •No symptomatic neurologic condition
- •No other uncontrolled serious medical condition
- •No other malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
- •No history of hypersensitivity to intravenous paclitaxel or other medication containing Cremophor EL or polysorbate 80 as a carrier (phase Ib)
- •Phase Ib only:
- •More than 4 weeks since prior immunotherapy
- •More than 4 weeks since prior biologic therapy
- •No concurrent immunotherapy
- •Phase Ib and II:
- •No concurrent prophylactic filgrastim (G-CSF)
- •Phase Ib only:
- •More than 1 year since prior adjuvant docetaxel before metastatic relapse
- •More than 4 weeks since prior chemotherapy and recovered
- •No prior capecitabine AND docetaxel (in combination or as single agents)
- •Prior capecitabine OR docetaxel allowed
- •No other concurrent chemotherapy
- •Phase II only:
- •No prior cytotoxic chemotherapy for breast cancer
- •Phase Ib only:
- •More than 3 weeks since prior radiotherapy
- 另有 12 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (tipifarnib, capecitabine, docetaxel)
Phase Ib: Patients receive oral tipifarnib twice daily and oral capecitabine twice daily on days 1-14 and docetaxel IV over 30-60 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Phase II: Patients receive oral tipifarnib twice daily for 6 days. Beginning at least 48 hours after completion of the initial dose of tipifarnib, patients receive treatment as in phase Ib for up to 6 courses at the MTD of capecitabine.
干预措施: Capecitabine (Drug)
Treatment (tipifarnib, capecitabine, docetaxel)
Phase Ib: Patients receive oral tipifarnib twice daily and oral capecitabine twice daily on days 1-14 and docetaxel IV over 30-60 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Phase II: Patients receive oral tipifarnib twice daily for 6 days. Beginning at least 48 hours after completion of the initial dose of tipifarnib, patients receive treatment as in phase Ib for up to 6 courses at the MTD of capecitabine.
干预措施: Docetaxel (Drug)
Treatment (tipifarnib, capecitabine, docetaxel)
Phase Ib: Patients receive oral tipifarnib twice daily and oral capecitabine twice daily on days 1-14 and docetaxel IV over 30-60 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Phase II: Patients receive oral tipifarnib twice daily for 6 days. Beginning at least 48 hours after completion of the initial dose of tipifarnib, patients receive treatment as in phase Ib for up to 6 courses at the MTD of capecitabine.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (tipifarnib, capecitabine, docetaxel)
Phase Ib: Patients receive oral tipifarnib twice daily and oral capecitabine twice daily on days 1-14 and docetaxel IV over 30-60 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Phase II: Patients receive oral tipifarnib twice daily for 6 days. Beginning at least 48 hours after completion of the initial dose of tipifarnib, patients receive treatment as in phase Ib for up to 6 courses at the MTD of capecitabine.
干预措施: Pharmacological Study (Other)
Treatment (tipifarnib, capecitabine, docetaxel)
Phase Ib: Patients receive oral tipifarnib twice daily and oral capecitabine twice daily on days 1-14 and docetaxel IV over 30-60 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Phase II: Patients receive oral tipifarnib twice daily for 6 days. Beginning at least 48 hours after completion of the initial dose of tipifarnib, patients receive treatment as in phase Ib for up to 6 courses at the MTD of capecitabine.
干预措施: Tipifarnib (Drug)
结局指标
主要结局
Dose-limiting toxicity (DLT) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 (Phase I)
时间窗: 21 days
Pathologic complete response rate (Phase II)
时间窗: Up to 5 years
Estimated by the number of patients with a complete pathologic response divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true pathologic complete response probability will be calculated according to the approach of Duffy and Santner.
次要结局
- Clinical tumor response (complete response [CR] or partial response [PR]) (Phase I)(Up to 5 years)
- Overall survival(From registration to death due to any cause, assessed up to 5 years)
- Toxicity as assessed by the National Cancer Institute (NCI) CTCAE version 3.0(Up to 5 years)