Radiation Therapy and Combination Chemotherapy in Treating Patients With Stage II or Stage III Bladder Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00003930
First received: November 1, 1999
Last updated: May 9, 2014
Last verified: May 2014
  Purpose

RATIONALE: Radiation therapy uses x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy and surgery may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of radiation therapy plus combination chemotherapy in treating patients who have stage II or stage III bladder cancer that can be removed by surgery.


Condition Intervention Phase
Bladder Cancer
Drug: cisplatin
Drug: gemcitabine hydrochloride
Drug: paclitaxel
Procedure: conventional surgery
Radiation: radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial in Patients With Muscle-Invading Bladder Cancer of Transurethral Surgery Plus Taxol, Cisplatin and Bid Irradiation Followed by Either Selective Bladder Preservation or Radical Cystectomy and Adjuvant Chemotherapy

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Completion and safety of induction chemo-radiotherapy followed by definitive local therapy of either radical cystectomy or consolidation TCI, followed by four cycles of outpatient adjuvant gemcitabine-cisplatin chemotherapy. [ Time Frame: From start to end of all protocol therapy ] [ Designated as safety issue: No ]
    Completion and safety of induction chemo-radiotherapy (cisplatin, paclitaxel and irradiation [TCI]) followed by definitive local therapy of either radical cystectomy (for patients for whom the initial tumor is not a complete response) or consolidation TCI (for patients for whom the initial tumor has cleared), followed by four cycles of outpatient adjuvant gemcitabine-cisplatin chemotherapy.


Secondary Outcome Measures:
  • Complete response after TCI induction [ Time Frame: From start to end of all protocol therapy ] [ Designated as safety issue: No ]
  • Completion and safety of the four cycles of gemcitabine-cisplatin chemotherapy [ Time Frame: From start to end of all protocol therapy ] [ Designated as safety issue: No ]
  • Invasive local treatment failure [ Time Frame: From start of protocol treatment to date of local failure. Analysis occurs after all patients have copmleted treatment. ] [ Designated as safety issue: No ]
  • Distant metastasis [ Time Frame: From start of protocol treatment to date of distant metastasis ] [ Designated as safety issue: No ]
  • To examine the value of tumor histopathology, molecular genetics and DNA flow cytometric parameters as possible significant prognostic factors for initial tumor response and recurrence-free survival. [ Time Frame: From the start of protocol treatment to the date the last patient has completed treatment. Analysis occurs after all patients have completed treatment. ] [ Designated as safety issue: No ]

Enrollment: 84
Study Start Date: September 1999
Study Completion Date: November 2013
Primary Completion Date: July 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Transurethral surgery with chemotherapy and radiation therapy followed by either selective bladder preservation or radical cystectomy followed by adjuvant chemotherapy.
Drug: cisplatin Drug: gemcitabine hydrochloride Drug: paclitaxel Procedure: conventional surgery Radiation: radiation therapy

Detailed Description:

OBJECTIVES:

  • Evaluate the safety and tolerability of induction chemoradiotherapy with paclitaxel and cisplatin followed by selective bladder preservation or radical cystectomy and adjuvant chemotherapy in patients with stage II or III muscle invasive carcinoma of the bladder previously treated with transurethral tumor resection.
  • Evaluate the efficacy of transurethral tumor resection and induction chemoradiotherapy in achieving a complete response in this patient population.
  • Assess the value of tumor parameters as prognostic factors for initial tumor response and recurrence-free survival in this patient population.

OUTLINE: Four to six weeks after prior transurethral resection, patients receive induction therapy comprising paclitaxel IV over 1 hour on days 1, 8, and 15, cisplatin IV over 1 hour on days 1, 2, 8, 9, 15, and 16, and radiotherapy twice daily on days 1-5, 8-12, and 17.

Four weeks after induction therapy, patients undergo urologic evaluation. At 1-2 weeks after evaluation, patients with complete response receive consolidation therapy comprising paclitaxel IV over 1 hour on days 1 and 8, cisplatin IV over 1 hour on days 1, 2, 8, and 9, and radiotherapy twice daily on days 1-5 and 8-10. Patients with poor tumor response undergo a cystectomy.

At 12 weeks postconsolidation therapy or 8 weeks post radical cystectomy, patients receive adjuvant chemotherapy comprising gemcitabine IV over 30-60 minutes followed by cisplatin IV over 1 hour every 3 weeks. Treatment repeats every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 84 patients will be accrued for this study within 3 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed stage II or III (T2-4a, Nx or N0, M0) primary carcinoma of the bladder with muscle invasion

    • Resectable disease
    • Prostatic urethral involvement with transitional cell carcinoma allowed, if completely resected and no evidence of stromal invasion
    • No tumor-related hydronephrosis
  • Positive lymph node must be evaluated by lymphadenectomy or percutaneous needle biopsy

    • No nodal metastases
  • No distant metastases
  • No more than 6 weeks since prior transurethral resection of the bladder tumor

    • Functioning bladder

PATIENT CHARACTERISTICS:

Age:

  • Adult

Performance status:

  • Zubrod 0-1

Life expectancy:

  • Not specified

Hematopoietic:

  • Hemoglobin at least 10 g/dL
  • White blood cell (WBC) count of at least 4,000/mm^3
  • Absolute neutrophil count at least 1,800/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic:

  • Bilirubin no greater than 2.0 mg/dL

Renal:

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

Other:

  • No other prior or concurrent malignancy within the past 5 years except curatively treated nonmelanoma skin cancer, stage I prostate cancer, or carcinoma in situ of the cervix
  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Medically operable

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 potential nephrotoxic or ototoxic drugs (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: NCT00003930

  Show 229 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
Investigators
Study Chair: Donald S. Kaufman, MD Massachusetts General Hospital
  More Information

Additional Information:
Publications:
Kaufman DS, Winter KA, Shipley WU, et al.: Muscle-invading bladder cancer, RTOG Protocol 99-06: initial report of a phase I/II trial of selective bladder-conservation employing TURBT, accelerated irradiation sensitized with cisplatin and paclitaxel followed by adjuvant cisplatin and gemcitabine chemotherapy. [Abstract] J Clin Oncol 23 (Suppl 16): A-4506, 379s, 2005.
Shipley WU, Bae K, Efstathiou JA, et al.: Late pelvic toxicity following bladder-sparing therapy in patients with invasive bladder cancer: analysis of RTOG 89-03, 95-06, 97-06, 99-06. [Abstract] Int J Radiat Oncol Biol Phys 69 (3 Suppl): A-14, S8, 2007.

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00003930     History of Changes
Other Study ID Numbers: RTOG-9906, CDR0000067122, RTOG-DEV-14321
Study First Received: November 1, 1999
Last Updated: May 9, 2014
Health Authority: United States: Federal Government

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
Gemcitabine
Cisplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on July 24, 2014