Chemotherapy and Radiation Therapy in Treating Patients With Stage II or Stage III Bladder Cancer That Was Removed by Surgery
|ClinicalTrials.gov Identifier: NCT00777491|
Recruitment Status : Active, not recruiting
First Posted : October 22, 2008
Last Update Posted : April 20, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Bladder Cancer||Drug: cisplatin Drug: fluorouracil Drug: gemcitabine hydrochloride Radiation: radiation therapy||Phase 2|
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- 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.
- 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.
Induction therapy (weeks 1-4):
- Arm I: Patients receive fluorouracil IV continuously over 72 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 undergo radiotherapy twice daily on days 1-5, 8-12, and 15-17.
- Arm II: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 4, 8, 11, 15, 18, 22, and 25. Patients also undergo radiotherapy once daily on days 1-5, 8-12, 15-19, and 22-26.
All patients undergo evaluation of response at 3-4 weeks after completion of induction therapy. Patients with pT1 or worse tumor response undergo radical cystectomy within 3-8 weeks after response evaluation. Patients with pT0, Ta, or Tis tumor response (at site distant from original tumor) proceed to consolidation therapy within 7-14 days after response evaluation.
Consolidation therapy (weeks 8-10):
- Arm I: Patients receive fluorouracil IV continuously over 72 hours on days 1-3 and 8-10 and cisplatin IV over 1 hour on days 1, 2, 8, and 9. Patients also undergo radiotherapy twice daily on days 1-5 and 8-10.
- Arm II: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 4, 8, 11, and 15. Patients also undergo radiotherapy once daily on days 1-5, 8-12, 15, and 16.
Patients proceed to adjuvant therapy 12 weeks after completion of consolidation therapy OR 8-12 weeks after radical cystectomy.
- Adjuvant therapy (weeks 21-33 or 17-29): Patients receive gemcitabine hydrochloride IV over 30-60 minutes on days 1 and 8 and cisplatin IV over 1 hour on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||64 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Study Start Date :||December 2008|
|Actual Primary Completion Date :||July 10, 2017|
|Estimated Study Completion Date :||January 2023|
U.S. FDA Resources
Experimental: Arm I
Patients receive induction therapy comprising fluorouracil IV, cisplatin IV, and radiotherapy in weeks 1-4. Patients then undergo either radical cystectomy or receive consolidation therapy comprising fluorouracil IV, cisplatin IV, and radiotherapy in weeks 8-10.
Given IVDrug: fluorouracil
Given IVRadiation: radiation therapy
Given once or twice daily
Experimental: Arm II
Patients receive induction therapy comprising gemcitabine hydrochloride IV and radiotherapy in weeks 1-4. Patients then undergo either radical cystectomy or receive consolidation therapy comprising gemcitabine hydrochloride IV and radiotherapy in weeks 8-10.
Drug: gemcitabine hydrochloride
Given IVRadiation: radiation therapy
Given once or twice daily
- Rate of distant metastasis at 3 years [ Time Frame: From date of randomization to the date of completion of the 3 year follow-up. ]
- Treatment completion rate [ Time Frame: From the date of randomization to the date when patients complete consolidation chemotherapy or have a cyctectome with four cycles of gemcitabine and cisplatin. ]
- Grade 3 or more genitourinary, gastrointestinal, and hematologic toxicities as assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0 [ Time Frame: Acute toxicities - From treatment start date to the end of treatment. Late adverse events - 180 days from the end of treatment. ]
- Complete response of the primary tumor [ Time Frame: Three to four weeks from completion of induction chemotherapy. ]
- Preservation of the native, tumor-free bladder 5 years after completion of study therapy [ Time Frame: Five years from the date of trasurethral surgery. ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00777491
|United States, Georgia|
|Georgia Cancer Center for Excellence at Grady Memorial Hospital|
|Atlanta, Georgia, United States, 30303|
|Winship Cancer Institute of Emory University|
|Atlanta, Georgia, United States, 30322|
|United States, Idaho|
|Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center|
|Boise, Idaho, United States, 83706|
|United States, Illinois|
|Cancer Institute at St. John's Hospital|
|Springfield, Illinois, United States, 62702|
|United States, Indiana|
|Parkview Regional Cancer Center at Parkview Health|
|Fort Wayne, Indiana, United States, 46805|
|United States, Maryland|
|St. Agnes Hospital Cancer Center|
|Baltimore, Maryland, United States, 21229|
|United States, Massachusetts|
|Hudner Oncology Center at Saint Anne's Hospital - Fall River|
|Fall River, Massachusetts, United States, 02721|
|United States, Michigan|
|Saint Joseph Mercy Cancer Center|
|Ann Arbor, Michigan, United States, 48106-0995|
|University of Michigan Comprehensive Cancer Center|
|Ann Arbor, Michigan, United States, 48109-0942|
|West Michigan Cancer Center|
|Kalamazoo, Michigan, United States, 49007-3731|
|McGill Cancer Centre at McGill University|
|Montreal, Quebec, Canada, H2W 1S6|
|Principal Investigator:||John J. Coen, MD||21st Century Oncology|
|Study Chair:||Philip J. Saylor, MD||Massachusetts General Hospital|
|Study Chair:||Cheryl T. Lee, MD||University of Michigan Cancer Center|
|Study Chair:||Chin-Lee Wu, MD, PhD||Massachusetts General Hospital|