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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: July 2003

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.

Interventions

  • Drug: cisplatin
  • Drug: gemcitabine hydrochloride
  • Drug: paclitaxel
  • Procedure: conventional surgery
  • Radiation: radiation therapy

Arms, Groups and Cohorts

  • Experimental: Arm 1
    • Transurethral surgery with chemotherapy and radiation therapy followed by either selective bladder preservation or radical cystectomy followed by adjuvant chemotherapy.

Clinical Trial Outcome Measures

Primary 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
    • 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 Measures

  • Complete response after TCI induction
    • Time Frame: From start to end of all protocol therapy
  • Completion and safety of the four cycles of gemcitabine-cisplatin chemotherapy
    • Time Frame: From start to end of all protocol therapy
  • Invasive local treatment failure
    • Time Frame: From start of protocol treatment to date of local failure. Analysis occurs after all patients have copmleted treatment.
  • Distant metastasis
    • Time Frame: From start of protocol treatment to date of distant metastasis
  • 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.

Participating in This Clinical Trial

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)

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Radiation Therapy Oncology Group
  • Collaborator
    • National Cancer Institute (NCI)
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Donald S. Kaufman, MD, Study Chair, Massachusetts General Hospital

References

Efstathiou JA, Bae K, Shipley WU, Kaufman DS, Hagan MP, Heney NM, Sandler HM. Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol. 2009 Sep 1;27(25):4055-61. doi: 10.1200/JCO.2008.19.5776. Epub 2009 Jul 27.

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.

Citations Reporting on Results

Kaufman DS, Winter KA, Shipley WU, Heney NM, Wallace HJ 3rd, Toonkel LM, Zietman AL, Tanguay S, Sandler HM. Phase I-II RTOG study (99-06) of patients with muscle-invasive bladder cancer undergoing transurethral surgery, paclitaxel, cisplatin, and twice-daily radiotherapy followed by selective bladder preservation or radical cystectomy and adjuvant chemotherapy. Urology. 2009 Apr;73(4):833-7. doi: 10.1016/j.urology.2008.09.036. Epub 2008 Dec 18.

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.

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.