NCT00777491

Chemotherapy and Radiation Therapy in Treating Patients With Stage II or Stage III Bladder Cancer That Was Removed by Surgery

A Phase II Randomized Study For Patients With Muscle-Invasive Bladder Cancer Evaluating Transurethral Surgery And Concomitant Chemoradiation By Either BID Irradiation Plus 5-Fluorouracil And Cisplatin Or QD Irradiation Plus Gemcitabine Followed By Selective Bladder Preservation And Gemcitabine/Cisplatin Adjuvant Chemotherapy

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 70 (actual)
• Sponsor: Radiation Therapy Oncology Group · Network
• Sex: All
• Age: 18 Years – 120 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Drugs used in chemotherapy, such as fluorouracil, cisplatin, and gemcitabine, 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. Giving chemotherapy together with radiation therapy may kill more tumor cells. PURPOSE: This randomized phase II trial is studying two different chemotherapy and radiation therapy regimens to see how they work in treating patients with stage II or stage III bladder cancer that was removed by surgery.

Detailed description

OBJECTIVES: Primary * To estimate the rate of distant metastasis at 3 years in patients who have undergone transurethral resection of the bladder tumor for stage II or III muscle-invasive bladder cancer treated with chemoradiotherapy comprising fluorouracil, cisplatin, and radiotherapy vs gemcitabine hydrochloride and radiotherapy followed by selective bladder preservation and adjuvant chemotherapy comprising gemcitabine hydrochloride and cisplatin. Secondary * To estimate the treatment completion rate in these patients. * To estimate acute and late grade toxicities (≥ grade 3 genitourinary, gastrointestinal, and hematologic toxicities) of these regimens in these patients. * To estimate the efficacy of these regimens, in terms of achieving complete response of the primary tumor, in these patients. * To estimate the efficacy of these regimens, in terms of preserving the native, tumor-free bladder 5 years after completion of therapy, in these patients. * To estimate the value of tumor histopathologic, molecular genetic, DNA content, metabolomic, and proteomic parameters as possible significant prognostic factors for initial tumor response and recurrence-free survival. * To analyze for American Urological Association (AUA) Symptom scores at baseline and at 3 years from patients on both arms. * To find potentially predictive biomarkers for cystectomy-free survival. * To find potentially predictive biomarkers for acute and late toxicities. OUTLINE: This is a multicenter study. Patients are stratified according to tumor stage (T2 vs T3-4a). Patients are randomized to 1 of 2 treatment arms.

Conditions

• Bladder Cancer

Interventions

Type	Name	Description
DRUG	induction cisplatin	15 mg/m\^2 administered as a 60-minute infusion on days 1,2,3,8,9,10,15,16,17.
DRUG	induction 5-fluorouracil	400mg/m\^2 administered as a 24-hour infusion on days 1,2,3, and 15,16,17.
DRUG	induction gemcitabine	27 mg/m\^2 administered as a 30-minute infusion on days 1, 4, 8, 11, 15, 18, 22, 25.
RADIATION	Induction BID radiation therapy	Twice daily (BID) on days 1-5,8-12,15-17. The first daily treatment consists of 1.6 Gy delivered to the pelvis. The second fraction consists of 1.5 Gy to the bladder for the first 5 treatment days. Then, 1.5 Gy is delivered to bladder tumor volume as the second treatment for the remaining 8 treatment days. The bladder tumor volume receives a total of 40.3 Gy.
RADIATION	Induction QD radiation therapy	Once daily (QD) on days (1-5,8-12,15-19,22-26). For the first 10 treatment days, 2 Gy is delivered to the pelvis. Then, 2 Gy is delivered to the bladder for the next 4 treatment days, followed by 2 Gy to the bladder tumor volume for the remaining 6 treatment days. The bladder tumor volume receives a total of 40 Gy.
RADIATION	Consolidation BID radiation therapy	Twice daily (BID) for 8 days on days 1,2,3,4,5,8,9,10 of consolidation. 1.5 Gy per fraction for a total of 24 Gy delivered to the pelvis.
RADIATION	Consolidation QD radiation therapy	Once daily (QD) pelvic radiation therapy for 12 days on days 1-5,8-12,15-16 of consolidation. 2 Gy per fraction for a total of 24 Gy delivered to the pelvis.
DRUG	consolidation gemcitabine	27 mg/m\^2 administered as a 30-minute infusion on days 1, 4, 8, 11, 15 of consolidation.
DRUG	consolidation 5-fluorouracil	400 mg/m\^2 administered as a 24-hour infusion on days 1, 2, 3 and 8, 9, 10 of consolidation.
DRUG	consolidation cisplatin	15 mg/m\^2 administered as a sixty-minute infusion on days 1, 2, 8, 9 of consolidation.
PROCEDURE	radical cystectomy	Operable patients who have a pT1 or worse tumor response on re-evaluation following initial transurethral resection and induction chemoradiotherapy will have a radical cystectomy 3-8 weeks following the post-induction response evaluation.
PROCEDURE	Post-Induction Chemoradiotherapy Endoscopic Response Evaluation	Urine cytology, cystoscopy, tumor site transurethral biopsy, and bimanual examination after biopsy.
DRUG	adjuvant gemcitabine	1000 mg/m\^2 administered intravenously over 30-60 minutes (preferably 30 minutes) on days 1 and 8 of each 21-day cycle for four cycles.
DRUG	adjuvant cisplatin	70 mg/m\^2 administered as a sixty-minute infusion on day 1 of each 21-day cycle for four cycles.

Timeline

• Start date: 2008-12-01
• Primary completion: 2018-02-18
• Completion: 2022-05-20
• First posted: 2008-10-22
• Last updated: 2022-06-15
• Results posted: 2019-08-21

Locations

11 sites across 2 countries: United States, Canada