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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

March 6, 2003
December 19, 2013
December 2002
October 2010   (final data collection date for primary outcome measure)
  • 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 ]
Not Provided
Complete list of historical versions of study NCT00055601 on ClinicalTrials.gov Archive Site
  • 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 ]
Not Provided
Not Provided
Not Provided
 
Combination Chemotherapy and Radiation Therapy With or Without Surgery In Treating Patients With Stage II or Stage III Bladder Cancer
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

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.

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.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Bladder Cancer
  • Drug: cisplatin
    Given IV
  • Drug: fluorouracil
    Given IV
  • Drug: paclitaxel
    Given IV
  • Radiation: radiation therapy
    Patients undergo pelvic radiotherapy.
  • Experimental: Pelvic RT + paclitaxel IV + cisplatin IV
    Pelvic radiation therapy + paclitaxal IV + cisplatin IV
    Interventions:
    • Drug: cisplatin
    • Drug: paclitaxel
    • Radiation: radiation therapy
  • Experimental: Pelvic RT + fluorouracil IV + cisplatin IV
    Pelvic radiation therapy + fluoruracil IV + cisplatin IV
    Interventions:
    • Drug: cisplatin
    • Drug: fluorouracil
    • Radiation: radiation therapy
Mitin T, Hunt D, Shipley WU, Kaufman DS, Uzzo R, Wu CL, Buyyounouski MK, Sandler H, Zietman AL. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. Lancet Oncol. 2013 Aug;14(9):863-72. doi: 10.1016/S1470-2045(13)70255-9. Epub 2013 Jul 1.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
97
Not Provided
October 2010   (final data collection date for primary outcome measure)

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)
Both
Not Provided
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00055601
RTOG 0233, CDR0000258303, ECOG-R0233, NCI-2011-01578
Yes
Radiation Therapy Oncology Group
Radiation Therapy Oncology Group
  • National Cancer Institute (NCI)
  • Eastern Cooperative Oncology Group
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
Radiation Therapy Oncology Group
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP