Chemotherapy and Radiation Therapy in Treating Patients With Stage II or Stage III Bladder Cancer That Was Removed by Surgery
Condition: Bladder Cancer
MeSH terms: Urinary Bladder Neoplasms
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): induction cisplatin; induction 5-fluorouracil; induction gemcitabine; Induction BID radiation therapy; Induction QD radiation therapy; Consolidation BID radiation therapy; Consolidation QD radiation therapy; consolidation gemcitabine; consolidation 5-fluorouracil; consolidation cisplatin; radical cystectomy; Post-Induction Chemoradiotherapy Endoscopic Response Evaluation; adjuvant gemcitabine; adjuvant cisplatin
Intervention type(s): Drug; Drug; Drug; Radiation; Radiation; Radiation; Radiation; Drug; Drug; Drug; Procedure; Procedure; Drug; Drug
Intervention description(s): 15 mg/m^2 administered as a 60-minute infusion on days 1,2,3,8,9,10,15,16,17.; 400mg/m^2 administered as a 24-hour infusion on days 1,2,3, and 15,16,17.; 27 mg/m^2 administered as a 30-minute infusion on days 1, 4, 8, 11, 15, 18, 22, 25.; 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.; 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.; 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.; 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.; 27 mg/m^2 administered as a 30-minute infusion on days 1, 4, 8, 11, 15 of consolidation.; 400 mg/m^2 administered as a 24-hour infusion on days 1, 2, 3 and 8, 9, 10 of consolidation.; 15 mg/m^2 administered as a sixty-minute infusion on days 1, 2, 8, 9 of consolidation.; 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.; Urine cytology, cystoscopy, tumor site transurethral biopsy, and bimanual examination after biopsy.; 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.; 70 mg/m^2 administered as a sixty-minute infusion on day 1 of each 21-day cycle for four cycles.
Other intervention name(s): fluorouracil; 5-FU; gemcitabine hydrochloride; gemcitabine hydrochloride; fluorouracil; 5-FU; cisplatin; TUR; gemcitabine hydrochloride
Intervention MeSH terms: Cisplatin; Gemcitabine; Fluorouracil
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage II bladder cancer; stage III bladder cancer; transitional cell carcinoma of the bladder