Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	Not specified	NCI	RTOG-0233 ECOG-R0233, NCT00055601

Objectives

1. 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.
2. Estimate the efficacy of these regimens, in terms of complete response, in patients who have undergone prior transurethral resection (TUR).
3. Estimate the efficacy of these regimens after TUR, in terms of preserving the native tumor-free bladder 5 years after therapy, in these patients.
4. Estimate the function of the preserved bladder in patients treated with these regimens after TUR.
5. 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.

Entry Criteria

Disease Characteristics:

• Histologically confirmed operable primary muscle invasive bladder cancer
  • T2-T4a, NX or N0, M0 (stage II or III)



• Must have an adequate functioning bladder



• Must have undergone a prior transurethral resection of the bladder tumor within the past 8 weeks



• No evidence of tumor-related hydronephrosis



• No evidence of distant metastases or histologically or cytologically confirmed lymph node metastases



• Patients with involvement of the prostatic urethra with transitional cell cancer that was visibly completely resected are allowed
  • No evidence of stromal invasion of the prostate

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• No prior systemic chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior pelvic radiotherapy

Surgery

• See Disease Characteristics

Other

• No concurrent drugs that have potential nephrotoxicity or ototoxicity (e.g., aminoglycosides)

Patient Characteristics:

Age

• Not specified

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Hemoglobin at least 10 g/dL
• WBC at least 4,000/mm³
• Absolute neutrophil count at least 1,800/mm³
• Platelet count at least 100,000/mm³

Hepatic

• Serum bilirubin no greater than 2.0 mg/dL

Renal

• Serum creatinine no greater than 1.5 mg/dL
• Creatinine clearance at least 60 mL/min

 [Note: If the creatinine clearance is greater than 60 mL/min, creatinine of no greater than 1.8 mg/dL is allowed at the discretion of the study chair]

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except nonmelanoma skin cancer, stage T1a prostate cancer, or carcinoma in situ of the cervix
• Must be able to tolerate systemic chemotherapy with pelvic radiotherapy and radical cystectomy

Expected Enrollment

A total of 96 patients (48 per treatment arm) will be accrued for this study within 3 years.

Outcomes

Completion rate
Safety

Complete response after induction
Bladder-intact survival
Bladder function
Value of tumor histopathology, molecular genetics, and DNA flow cytometric parameters

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 for 8 days.
  
  
  
  • 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.

Trial Contact Information

Trial Lead Organizations

Radiation Therapy Oncology Group

Anthony Zietman, MD, Protocol chair		Ph: 617-724-1158; 877-726-5130
Robert Uzzo, MD, Protocol co-chair		Ph: 215-728-3501; 888-369-2427

Eastern Cooperative Oncology Group

Robert Dreicer, MD, FACP, Protocol chair		Ph: 216-445-4623; 800-862-7798 Email: dreicer@ccf.org

Registry Information
Official Title		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
Trial Start Date		2002-12-13
Trial Completion Date		2008-08-27 (estimated)
Registered in ClinicalTrials.gov		NCT00055601
Date Submitted to PDQ		2002-10-03
Information Last Verified		2008-10-27
NCI Grant/Contract Number		CA21661

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