A Phase III Study of Paclitaxel Via Weekly 1 Hour Infusion Versus Standard 3 Hour Infusion Every 3 Weeks With Herceptin (Trastuzumab) (NSC #688097) in the Treatment of Patients With/Without HER-2/Neu-Overexpressing Metastatic Breast Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 580
- 试验地点
- 1
- 主要终点
- Response rate (complete response [CR]) and partial response [PR])
研究概览
简要总结
This randomized phase III studies how well two different regimens of paclitaxel with or without trastuzumab works in treating patients with or without HER-2/Neu breast cancer that is inoperable, recurrent, or metastatic. Drugs used in chemotherapy, such as paclitaxel, use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as trastuzumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known what regimen of paclitaxel is more effective with or without trastuzumab in treating patients with breast cancer.
详细描述
PRIMARY OBJECTIVES:
I. To determine whether "dose dense" (DD) treatment with paclitaxel via weekly 1-hour infusion has a significantly higher response rate than "standard" (S) paclitaxel treatment, regardless of human epidermal growth factor receptor 2 (HER-2/neu) status and assignment to Herceptin (trastuzumab).
II. To determine if the addition of Herceptin to DD or S paclitaxel significantly improves the response rate as compared to DD or S paclitaxel alone for HER-2/neu non-overexpressing metastatic breast cancer (e.g., 0 or 1+).
III. To determine whether the addition of Herceptin to chemotherapy treatment modifies the quality of life experienced by patients with HER-2/neu non-overexpressing metastatic breast cancer.
IV. To determine whether the quality of life experienced by patients with metastatic breast cancer who have been treated with "standard" paclitaxel treatment differ from that of patients treated with "dose dense" paclitaxel treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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 confirmed adenocarcinoma of the female breast which is inoperable, recurrent or metastatic
- •HER-2/neu status must be known at the time of protocol registration; HER-2/neu assessment will be based on FISH analysis of either the primary tumor or a metastatic site; a scoring of 0 or 1+ by immunohistochemistry (IHC) is considered negative; 2+ is considered negative unless confirmed by FISH positivity, in which case it should be considered positive; 3+ by IHC is considered positive; for centers using FISH only, a positive FISH assay by itself is sufficient to determine HER-2 positivity
- •Patients with the following prior therapy are eligible:
- •Patients with 0-1 prior chemotherapy regimens for metastatic or locally advanced breast cancer, with the following exception: no prior taxane for metastatic/locally advanced breast cancer
- •Patients with 0-1 prior chemotherapy regimens in the adjuvant setting; if adjuvant regimen included a taxane, patient must have been disease free for at least 12 months from completion of adjuvant therapy until relapse
- •Patients must be > 2 weeks from prior surgery, other than simple biopsy or placement of venous access device; patients must be > 4 weeks from prior chemotherapy; patients must be >6 weeks from nitrosoureas, melphalan, or mitomycin
- •Patients must be > 4 weeks from prior hormonal therapy unless tumor measurements document clear progression while on treatment; if progression is documented and toxicity from hormonal regimen has resolved, patients may be placed on study > 1 week from prior hormonal therapy
- •Prior Herceptin therapy is not allowed
- •Patients with central nervous system metastases are eligible only if the patient has completed cranial irradiation at least 6 months prior, is currently asymptomatic, and is not currently receiving corticosteroids for this condition; patients with leptomeningeal carcinoma (carcinomatous meningitis) are not eligible
- •MESURABLE DISEASE: Any mass reproducibly measurable in two perpendicular dimensions, examples include:
- •Pulmonary nodules
- •Hepatic lesions
- •Skin nodules (if two measurements can be assigned)
- •Lymph nodes
- •The following lesions do not qualify as measurable:
- •Central nervous system (CNS) lesions
- •Bone disease only; lytic lesions should be documented and followed
- •Lymphangitic pulmonary metastases (patients with lymphangitic metastases are eligible if there are other sites of metastatic disease which can be measured)
- •Lesions which have been irradiated unless there is definite documentation of progression since radiotherapy
- •A baseline assessment of left ventricular ejection fraction within 8 weeks of registration is required (echocardiogram or resting multi gated acquisition scan [MUGA] (radionuclide cineangiography [RNCA]) nuclear scintigraphy); patients with a left ventricular ejection fraction (LVEF) < 45% are ineligible
- •Granulocytes >= 1500/ul
- •Platelet count >= 100,000/ul
- •Creatinine =< 2.0 mg/dl
- •Bilirubin within institutional normal limits
- •Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST])
排除标准
- 未提供
研究组 & 干预措施
Arm A (paclitaxel)
Patients receive paclitaxel intravenously (IV) over 3 hours every 3 weeks.
干预措施: paclitaxel (Drug)
Arm A (paclitaxel)
Patients receive paclitaxel intravenously (IV) over 3 hours every 3 weeks.
干预措施: quality-of-life assessment (Procedure)
Arm A (paclitaxel)
Patients receive paclitaxel intravenously (IV) over 3 hours every 3 weeks.
干预措施: laboratory biomarker analysis (Other)
Arm B (paclitaxel)
Patients receive paclitaxel IV over 1 hour weekly.
干预措施: paclitaxel (Drug)
Arm B (paclitaxel)
Patients receive paclitaxel IV over 1 hour weekly.
干预措施: quality-of-life assessment (Procedure)
Arm B (paclitaxel)
Patients receive paclitaxel IV over 1 hour weekly.
干预措施: laboratory biomarker analysis (Other)
Arm C (paclitaxel, trastuzumab)
Patients receive paclitaxel as in Arm I. Patients also receive trastuzumab IV weekly.
干预措施: paclitaxel (Drug)
Arm C (paclitaxel, trastuzumab)
Patients receive paclitaxel as in Arm I. Patients also receive trastuzumab IV weekly.
干预措施: trastuzumab (Biological)
Arm C (paclitaxel, trastuzumab)
Patients receive paclitaxel as in Arm I. Patients also receive trastuzumab IV weekly.
干预措施: quality-of-life assessment (Procedure)
Arm C (paclitaxel, trastuzumab)
Patients receive paclitaxel as in Arm I. Patients also receive trastuzumab IV weekly.
干预措施: laboratory biomarker analysis (Other)
Arm D (paclitaxel, trastuzumab)
Patients receive paclitaxel as in Arm II and trastuzumab as in Arm III.
干预措施: paclitaxel (Drug)
Arm D (paclitaxel, trastuzumab)
Patients receive paclitaxel as in Arm II and trastuzumab as in Arm III.
干预措施: trastuzumab (Biological)
Arm D (paclitaxel, trastuzumab)
Patients receive paclitaxel as in Arm II and trastuzumab as in Arm III.
干预措施: quality-of-life assessment (Procedure)
Arm D (paclitaxel, trastuzumab)
Patients receive paclitaxel as in Arm II and trastuzumab as in Arm III.
干预措施: laboratory biomarker analysis (Other)
Am E (paclitaxel, trastuzumab)
Patients receive paclitaxel and trastuzumab as in Arm C.
干预措施: paclitaxel (Drug)
Am E (paclitaxel, trastuzumab)
Patients receive paclitaxel and trastuzumab as in Arm C.
干预措施: trastuzumab (Biological)
Am E (paclitaxel, trastuzumab)
Patients receive paclitaxel and trastuzumab as in Arm C.
干预措施: quality-of-life assessment (Procedure)
Am E (paclitaxel, trastuzumab)
Patients receive paclitaxel and trastuzumab as in Arm C.
干预措施: laboratory biomarker analysis (Other)
Arm F (paclitaxel, trastuzumab)
Patients receive paclitaxel and trastuzumab as in Arm D.
干预措施: paclitaxel (Drug)
Arm F (paclitaxel, trastuzumab)
Patients receive paclitaxel and trastuzumab as in Arm D.
干预措施: trastuzumab (Biological)
Arm F (paclitaxel, trastuzumab)
Patients receive paclitaxel and trastuzumab as in Arm D.
干预措施: quality-of-life assessment (Procedure)
Arm F (paclitaxel, trastuzumab)
Patients receive paclitaxel and trastuzumab as in Arm D.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Response rate (complete response [CR]) and partial response [PR])
时间窗: Up to 5 years
Multivariate logistic regression will be used to relate patient characteristics and pretreatment clinical variables with tumor response (complete or partial). Interim analyses will use a chi square statistic to compare response incidence by treatment arm with two-sided bounds constructed from the O'Brien-Fleming approach
次要结局
- Overall survival(Up to 5 years)
- Time to disease progression:(Up to 5 years)
- Duration of response(Length of time between response and disease progression, assessed up to 5 years)
- Cardiac toxicity as measured by changes in LVEF(From baseline to up to 5 years)
- Toxicity as assessed by CALGB Expanded Common Toxicity Criteria(Up to 5 years)
- Change in quality of life (QOL)(From baseline to up to 9 months)
- Correlation between ErbB2 and response to treatment(Up to 5 years)