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

Sponsor:	Radiation Therapy Oncology Group
Collaborators:	National Cancer Institute (NCI) Eastern Cooperative Oncology Group
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00055601

Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy 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.

Condition	Intervention	Phase
Bladder Cancer	Drug: cisplatin Drug: fluorouracil Drug: paclitaxel Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: bladder cancer

MedlinePlus related topics: Bladder Cancer Cancer

Drug Information available for: Fluorouracil Cisplatin Paclitaxel

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Completion rate [ Designated as safety issue: No ]
Safety [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Complete response after induction [ Designated as safety issue: No ]
Bladder-intact survival [ Designated as safety issue: No ]
Bladder function [ Designated as safety issue: No ]
Value of tumor histopathology, molecular genetics, and DNA flow cytometric parameters [ Designated as safety issue: No ]

Estimated Enrollment:	96
Study Start Date:	December 2002
Estimated Primary Completion Date:	August 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm I (induction therapy) 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.	Drug: cisplatin Given IV Drug: paclitaxel Given IV Radiation: radiation therapy Patients undergo pelvic radiotherapy.
Experimental: Arm II (induction therapy) 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.	Drug: cisplatin Given IV Drug: fluorouracil Given IV Radiation: radiation therapy Patients undergo pelvic radiotherapy.
Experimental: Arm I (consolidation therapy) 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.	Drug: cisplatin Given IV Drug: paclitaxel Given IV Radiation: radiation therapy Patients undergo pelvic radiotherapy.
Experimental: Arm II (consolidation therapy) 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.	Drug: cisplatin Given IV Drug: fluorouracil Given IV Radiation: radiation therapy Patients undergo pelvic radiotherapy.

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 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.

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

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

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/mm^3
Absolute neutrophil count at least 1,800/mm^3
Platelet count at least 100,000/mm^3

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

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00055601

Locations

United States, Utah
LDS Hospital
Salt Lake City, Utah, United States, 84103
Utah Cancer Specialists at UCS Cancer Center
Salt Lake City, Utah, United States, 84106

Sponsors and Collaborators

Radiation Therapy Oncology Group

National Cancer Institute (NCI)

Eastern Cooperative Oncology Group

Investigators

Study Chair:	Anthony L. Zietman, MD	Massachusetts General Hospital
Investigator:	Robert Uzzo, MD	Fox Chase Cancer Center
Study Chair:	Robert Dreicer, MD, FACP	The Cleveland Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Walter John Curran, Jr, Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:	NCT00055601 History of Changes
Other Study ID Numbers:	CDR0000258303, RTOG-0233, ECOG-R0233
Study First Received:	March 6, 2003
Last Updated:	April 14, 2009
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage II bladder cancer
stage III bladder cancer

Additional relevant MeSH terms:

Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Cisplatin
Fluorouracil
Paclitaxel
Antineoplastic Agents
Therapeutic Uses

Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on February 12, 2012