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
Overview
- Phase
- Phase 1
- Intervention
- Paclitaxel
- Conditions
- Bladder Urothelial Carcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 70
- Locations
- 183
- Primary Endpoint
- Acute Treatment-related Toxicity
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
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.
Detailed Description
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. III. To measure the 5-year disease-free and overall survival of patients with bladder cancer treated with transurethral resection of the bladder followed by chemoradiotherapy. IV. To estimate the value of tumor and/or serum biomarkers as predictors of initial tumor response and recurrence-free survival. OUTLINE: This is a non-randomized, multicenter study. Patients are assigned to 1 of 2 treatment groups according to HER2/neu status (HER2/neu 2+ or 3+ staining \[group 1\] vs HER2/neu 0 or 1+ staining \[group 2\]). GROUP I: Patients receive paclitaxel intravenously (IV) over 1 hour on days 1, 8, 15, 22, 29, 36, and 43 and trastuzumab (Herceptin®) 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. GROUP II: Patients receive paclitaxel and undergo radiotherapy as in group 1. After completion of study treatment, patients are followed at 4-5 weeks, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- Not provided
Arms & Interventions
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.
Intervention: Paclitaxel
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.
Intervention: Radiation Therapy
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.
Intervention: Trastuzumab
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.
Intervention: Paclitaxel
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.
Intervention: Radiation Therapy
Outcomes
Primary Outcomes
Acute Treatment-related Toxicity
Time Frame: 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.
Secondary Outcomes
- 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)