A Phase I/II Trial of a Combination of Paclitaxel and Trastuzumab With Daily Irradiation or Paclitaxel Alone With Daily Irradiation Following Transurethral Surgery for Non-Cystectomy Candidates With Muscle-Invasive Bladder Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 70
- 试验地点
- 183
- 主要终点
- Acute Treatment-related Toxicity
研究概览
简要总结
This phase I/II trial is studying the side effects of giving paclitaxel together with radiation therapy with or without trastuzumab and to see how well it works to kill any remaining tumor cells in patients who have undergone surgery for bladder cancer. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Paclitaxel may also make tumor cells more sensitive to radiation therapy. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving paclitaxel together with radiation therapy and trastuzumab may kill more tumor cells. Giving these treatments after surgery may kill any remaining tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine the acute toxicity (=< 90 days from protocol treatment start) from chemoradiotherapy including paclitaxel +/- trastuzumab and irradiation in non-cystectomy patients with or without her2/neu overexpression.
SECONDARY OBJECTIVES:
I. To determine the ability of patients with bladder cancer who are non-cystectomy candidates to complete this treatment program.
II. To evaluate the efficacy of this treatment program in achieving a complete response of the primary tumor.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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 primary transitional cell carcinoma (TCC) of the bladder
- •Histologic evidence of muscularis propria invasion
- •Meets 1 of the following stage criteria:
- •Stage T2-4a; NX, N0, or N1; and M0 disease
- •Clinical stage T1, grade 3/3 disease AND requires definitive local therapy
- •Tumor involvement of the prostatic urethra allowed provided the following criteria are met:
- •Tumor was visibly completely resected
- •No evidence of stromal invasion of the prostate
- •No evidence of distant metastases by chest x-ray (or chest CT scan) within 8 weeks prior to registration
- •No evidence of distant metastases by abdominal/pelvic CT scan (or MRI scan) within 8 weeks prior to registration
- •Has undergone transurethral bladder resection (as thorough as is judged safely possible) within the past 3-8 weeks, including bimanual examination with tumor mapping
- •Sufficient tumor tissue available for HER2/neu analysis
- •Not a candidate for radical cystectomy
- •Performance status - Zubrod 0-2
- •Absolute neutrophil count >= 1,800/mm^3
- •Platelet count >= 100,000/mm^3
- •Hemoglobin >= 8.0 g/dL (transfusion or other intervention allowed)
- •Bilirubin < 2.0 mg/dL
- •Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) < 2.5 times upper limit of normal
- •No hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
- •Creatinine =< 3.0 mg/dL
- •Left ventricular ejection fraction (LVEF) >= 40% by multigated acquisition scan (MUGA) scan or echocardiogram
- •No unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
- •No transmural myocardial infarction within the past 6 months
- •Not pregnant or nursing
- •No nursing for 6 months after completion of study treatment (for patients receiving trastuzumab [Herceptin®])
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for 6 months after completion of study treatment
- •Able to tolerate systemic chemotherapy and pelvic radiotherapy
- •No other invasive malignancy within the past 3 years except nonmelanoma skin cancer
- •No history of allergic reaction to study drugs
- •No history of inflammatory bowel disease
- •No acute bacterial or fungal infection requiring IV antibiotics
- •No other severe active comorbidity
- •No prior systemic chemotherapy with anthracyclines or taxanes
- •No prior systemic chemotherapy for TCC
- •No prior pelvic radiotherapy
排除标准
- 未提供
研究组 & 干预措施
Group I (paclitaxel, trastuzumab, radiation therapy)
Patients receive paclitaxel IV over 1 hour on days 1, 8, 15, 22, 29, 36, and 43 and trastuzumab IV over 90 minutes on day 1 and then over 30 minutes on days 8, 15, 22, 29, 36, and 43. Patients also undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, 43-47, and 50. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: Paclitaxel (Drug)
Group I (paclitaxel, trastuzumab, radiation therapy)
Patients receive paclitaxel IV over 1 hour on days 1, 8, 15, 22, 29, 36, and 43 and trastuzumab IV over 90 minutes on day 1 and then over 30 minutes on days 8, 15, 22, 29, 36, and 43. Patients also undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, 43-47, and 50. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: Radiation Therapy (Radiation)
Group I (paclitaxel, trastuzumab, radiation therapy)
Patients receive paclitaxel IV over 1 hour on days 1, 8, 15, 22, 29, 36, and 43 and trastuzumab IV over 90 minutes on day 1 and then over 30 minutes on days 8, 15, 22, 29, 36, and 43. Patients also undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, 43-47, and 50. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: Trastuzumab (Biological)
Group II (paclitaxel, radiation therapy)
Patients receive paclitaxel and undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, 43-47, and 50.
干预措施: Paclitaxel (Drug)
Group II (paclitaxel, radiation therapy)
Patients receive paclitaxel and undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, 43-47, and 50.
干预措施: Radiation Therapy (Radiation)
结局指标
主要结局
Acute Treatment-related Toxicity
时间窗: From start of protocol treatment to 90 days
In each group, the number of patients was tabulated by type and grade (gr) of treatment-related toxicity (CTCAE v3.0). Only the following types of toxicity within 90 days of treatment start were considered: ≥ gr4 neutropenia, ≥ gr4 febrile neutropenia, ≥ gr3 diarrhea, ≥ gr3 nausea/vomiting, ≥ gr3 thrombocytopenia, ≥ gr3 renal, pulmonary, hepatic, or neurologic toxicity, ≥ gr3 rectal or genitourinary bleeding, ≥ gr3 left ventricular failure, or ≥ gr2 other cardiac toxicity. The study was designed to estimate the rate of acute treatment-related toxicity separately in each group of patients. Using the Fleming's one-sample multiple test procedure with Type I and II errors each set at 10%, 40 cases/group were required to reject the null hypothesis that the true toxicity rate is greater than 25% in favor of the alternative hypothesis that the true rate is no more than 10%. Six or more patients with the designated toxicities out of 40 would result in rejecting the null hypothesis.
次要结局
- Treatment Completion(From registration to end of treatment; up to 64 days.")
- Complete Response to Treatment(At 12 weeks from treatment start)
- Progression-free Survival(From start of treatment to last follow-up. Maximum follow-up at time of analysis was 9.9 years.)
- Overall Survival(From the date of treatment started to death, assessed up to at least 5 years)