NCT00055601

Combination Chemotherapy and Radiation Therapy With/Without Surgery In Patients With Stage II/III Bladder Cancer

A Phase II Randomized Trial for Patients With Muscle-Invading Bladder Cancer Evaluating Transurethral Surgery and BID Irradiation Plus Either Paclitaxel and Cisplatin or 5-Fluorouracil and Cisplatin Followed by Selective Bladder Preservation and Gemcitabine/Paclitaxel/Cisplatin Adjuvant Chemotherapy

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 97 (actual)
• Sponsor: Radiation Therapy Oncology Group · Network
• Sex: All
• Age: 120 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy (RT) uses high-energy x-rays to damage tumor cells. It is not yet known which regimen of combination chemotherapy plus radiation therapy with or without surgery is more effective in treating bladder cancer. PURPOSE: Randomized phase II trial to study the effectiveness of two combination chemotherapy regimens and radiation therapy with or without radical cystectomy in treating patients who have stage II or stage III bladder cancer.

Detailed description

OBJECTIVES: * Estimate the safety and tolerability of induction paclitaxel, cisplatin, and radiotherapy or fluorouracil, cisplatin, and radiotherapy followed by consolidation chemoradiotherapy or radical cystectomy and adjuvant gemcitabine, paclitaxel, and cisplatin in patients with operable stage II or III bladder cancer. * Estimate the efficacy of these regimens, in terms of complete response, in patients who have undergone prior transurethral resection (TUR). * Estimate the efficacy of these regimens after TUR, in terms of preserving the native tumor-free bladder 5 years after therapy, in these patients. * Estimate the function of the preserved bladder in patients treated with these regimens after TUR. * Determine the value of tumor histopathologic, molecular genetic, and DNA content parameters as possible prognostic factors for initial tumor response and recurrence-free survival in patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to T stage (T2 vs T3/T4 ). Patients are randomized to one of two treatment arms. * Induction therapy (weeks 1-3): * Arm I: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and cisplatin IV over 1 hour on days 1-3, 8-10, and 15-17. Patients also receive pelvic radiotherapy twice daily on days 1-5, 8-12, and 15-17. * Arm II: Patients receive fluorouracil IV over 24 hours on days 1-3 and 15-17 and cisplatin IV over 1 hour on days 1-3, 8-10, and 15-17. Patients also receive pelvic radiotherapy as in arm I. Patients in both arms who achieve complete response after induction therapy proceed to consolidation therapy on week 8. Patients with operable pT1 or worse tumor response proceed to radical cystectomy on week 9. * Consolidation therapy (weeks 8 and 9): * Arm I: Patients receive paclitaxel IV over 1 hour on days 1 and 8 and cisplatin IV over 1 hour on days 1, 2, 8, and 9. Patients also receive pelvic radiotherapy twice daily on days 1-5 and 8-10. * Arm II: Patients receive 5-FU IV over 24 hours on days 1-3 and 8-10 and cisplatin as in arm I. Patients also receive radiotherapy as in arm I. * Adjuvant chemotherapy (weeks 21-33 or 17-29): Beginning 12 weeks after consolidation therapy or 8 weeks after radical cystectomy, patients receive gemcitabine IV over 30-60 minutes, paclitaxel IV over 1 hour, and cisplatin IV over 1 hour on days 1 and 8. Treatment repeats every 3 weeks for 4 courses. Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 96 patients (48 per treatment arm) will be accrued for this study within 3 years.

Conditions

• Bladder Cancer

Interventions

Type	Name	Description
DRUG	cisplatin	Induction: 15 mg/m2 as a 60-minute infusion on days 1, 2, 3, 8, 9, 10, 15, 16, and 17; Consolidation: 15 mg/m2 as a 60-minute infusion on days 1, 2, 8, and 9; Adjuvant: 35 mg/m2 as a 60-minute infusion on days 1 and 8 of each 21-day cycle for 4 cycles.
DRUG	fluorouracil	Induction: 400 mg/m2 as a 24-hour infusion on days 1, 2, 3, 15, 16, and 17; Consolidation: 400 mg/m2 as a 24-hour infusion on days 1, 2, 3, 8, 9, and 10.
DRUG	paclitaxel	Induction: 50 mg/m2 as a 60-minute infusion on days 1, 8, and 15; Consolidation: 50 mg/m2 as a 60-minute infusion on days 1 and 8; Adjuvant: 50 mg/m2 as a 60-minute infusion on days 1 and 8 of each 21-day cycle for 4 cycles.
RADIATION	radiation therapy	Induction: External beam irradiation, 1.6 Gy, will be given to the pelvis in the first treatment followed by an interfraction period of at least 4-6 hours. During the second treatment, 1.5 Gy will be delivered to the whole bladder for the first five sessions (7.5 Gy) then to the tumor plus a margin for eight sessions (12. Gy). Consolidation: Consolidation therapy will start 7-14 days following a cystoscopic re-evaluation demonstrating a complete response to the induction therapy. 1.5 Gy (per fraction) will be given to the pelvis in two treatment fractions per day, with an interfraction period of at least 4-6 hours.
DRUG	Gemcitabine	Adjuvant: 1000 mg/m2 over 30-60 minutes on days 1 and 8 of each 21-day cycle for 4 cycles.
PROCEDURE	Radical cystectomy	Operable patients with pT1 or worse tumor response on re-evaluation following induction therapy will have radical cystectomy.

Timeline

• Start date: 2002-12-01
• Primary completion: 2010-10-01
• Completion: 2018-05-14
• First posted: 2003-03-07
• Last updated: 2018-06-15
• Results posted: 2016-08-10

Locations

2 sites across 1 country: United States