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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Eastern Cooperative Oncology Group
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00055601
First received: March 6, 2003
Last updated: December 19, 2013
Last verified: December 2013
  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 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
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:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Completion rate [ Time Frame: Within 11 weeks of randomization ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: Within 11 weeks of randomization ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Complete response after induction [ Time Frame: Four weeks after induction chemoradiation therapy ] [ Designated as safety issue: No ]
  • Bladder-intact survival [ Time Frame: From randomization to the time of cyctectomy, death or last follow-up. ] [ Designated as safety issue: No ]

Enrollment: 97
Study Start Date: December 2002
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pelvic RT + paclitaxel IV + cisplatin IV
Pelvic radiation therapy + paclitaxal IV + cisplatin IV
Drug: cisplatin
Given IV
Drug: paclitaxel
Given IV
Radiation: radiation therapy
Patients undergo pelvic radiotherapy.
Experimental: Pelvic RT + fluorouracil IV + cisplatin IV
Pelvic radiation therapy + fluoruracil IV + cisplatin IV
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Eastern Cooperative Oncology Group
Investigators
Principal Investigator: Anthony L. Zietman, MD Massachusetts General Hospital
Study Chair: Robert Uzzo, MD Fox Chase Cancer Center
Study Chair: Robert Dreicer, MD, FACP The Cleveland Clinic
  More Information

Additional Information:
No publications provided by Radiation Therapy Oncology Group

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00055601     History of Changes
Other Study ID Numbers: RTOG 0233, CDR0000258303, ECOG-R0233, NCI-2011-01578
Study First Received: March 6, 2003
Last Updated: December 19, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Radiation Therapy Oncology Group:
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
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on September 14, 2014