Radiation Therapy and Chemotherapy in Treating Patients With Stage I Bladder Cancer

This study is currently recruiting participants.
Verified September 2012 by National Cancer Institute (NCI)
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00981656
First received: September 19, 2009
Last updated: September 26, 2012
Last verified: September 2012
  Purpose

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin, mitomycin C, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with cisplatin may kill more tumor cells.

PURPOSE: This phase II trial is studying how well radiation therapy given together with chemotherapy works in treating patients with stage I bladder cancer.


Condition Intervention Phase
Bladder Cancer
Drug: cisplatin
Drug: fluorouracil
Drug: mitomycin C
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Protocol for Patients With Stage T1 Bladder Cancer to Evaluate Selective Bladder Preserving Treatment by Radiation Therapy Concurrent With Radiosensitizing Chemotherapy Following a Thorough Transurethral Surgical Re-Staging

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Rate of freedom from radical cystectomy at 3 years [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Rate of freedom from radical cystectomy at 5 years [ Designated as safety issue: No ]
  • Rate of freedom from the development of distant disease progression at 3 and 5 years [ Designated as safety issue: No ]
  • Rate of freedom from progression of bladder tumor to stage T2 or greater at 3 and 5 years [ Designated as safety issue: No ]
  • Disease-specific survival at 5 years [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Incidence of adverse events as assessed by CTCAE, v3.0 [ Designated as safety issue: Yes ]
  • Recurrence rate of any local bladder tumor [ Designated as safety issue: No ]
  • Collection of pretreatment and post-treatment tissue, blood, and urine specimens for translational studies and for correlation with response and clinical outcome [ Designated as safety issue: No ]
  • Descriptive analysis for American Urological Association symptom score at baseline and at 3 years [ Designated as safety issue: No ]

Estimated Enrollment: 37
Study Start Date: November 2009
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regimen I
Patients receive cisplatin IV on days 1-3 of weeks 1, 3, and 5.
Drug: cisplatin
Given IV
Experimental: Regimen II
Patients receive mitomycin C IV on day 1 of radiotherapy and fluorouracil IV continuously over days 1-5 of weeks 1 and 4.
Drug: fluorouracil
Given IV
Drug: mitomycin C
Given IV

Detailed Description:

OBJECTIVES:

Primary

  • To evaluate the rate of freedom from radical cystectomy at 3 years.

Secondary

  • To evaluate the rate of freedom from radical cystectomy at 5 years.
  • To evaluate the rate of freedom from the development of distant disease progression at 3 and 5 years.
  • To evaluate the rate of freedom from progression of bladder tumor to stage T2 or greater at 3 and 5 years.
  • To evaluate disease-specific survival and overall survival.
  • To evaluate the incidence of acute and late pelvic toxicity.
  • To evaluate the efficacy of this treatment approach in preventing the recurrence of any local bladder tumor.
  • To evaluate the potential value of tumor histopathology plus molecular genetic, DNA content, and urine proteomics parameters as possible significant prognostic factors for tumor control with this treatment approach.
  • To collect American Urological Association symptom scores at baseline and at 3 years.

OUTLINE: Beginning within 10 weeks of transurethral resection of the bladder tumor, patients undergo 3-dimensional conformal radiotherapy once daily 5 days per week during weeks 1-7 (34 fractions). Patients also receive 1 of 2 radiosensitizing chemotherapy regimens concurrently with radiotherapy.

  • Regimen I: Patients receive cisplatin IV on days 1-3 of weeks 1, 3, and 5.
  • Regimen II: Patients receive mitomycin C IV on day 1 of radiotherapy and fluorouracil IV continuously over days 1-5 of weeks 1 and 4.

Patients with a persistent tumor on re-evaluation may undergo radical cystectomy.

Tissue, blood, and urine samples may be collected periodically for biomarker and other analysis.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and annually thereafter.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Carcinoma of the bladder pathologically (histologically or cytologically) diagnosed within the past 10 weeks, meeting either of the following criteria:

    • Patients with operable tumors that are primary transitional cell carcinoma of the bladder exhibiting histologic evidence of invasion into the lamina propria (disease clinical stage T1) without evidence of muscularis propria invasion (muscularis propria must be present in the transurethral resection of the bladder tumor [TURBT] specimen) and are AJCC clinical stage T1, NX or N0, M0 without hydronephrosis
    • Patients with disease involvement of the prostatic urethra with transitional cell carcinoma and have no evidence of stromal invasion of the prostate
  • No pN+ or > T1 disease
  • No histologically or cytologically confirmed node metastases

    • If radiologic evaluation of a lymph node is interpreted as "positive", this must be evaluated further either by lymphadenectomy or by percutaneous needle biopsy
  • No evidence of distant metastases
  • Must have a T1G2 or T1G3 transitional cell carcinoma that has recurred within 18 months after initial treatment for ≤ T1 tumors (TURBT and intravesical BCG immunotherapy) or have presented to a participating urologist who judged BCG therapy is contraindicated because patient may be immunocompromised
  • Patients for whom radical cystectomy is the standard next therapy per urologic guidelines, in the judgement of the participating urologist, are eligible
  • Must have an adequately functioning bladder as judged by the participating urologist and radiation oncologist and have undergone a visibly complete re-staging TURBT by the participating urologist that shows (or is present on the outside pathology specimen) a T1G2 or T1G3 tumor with uninvolved muscularis propria in the specimen and, if on prostatic urethral biopsy mucosal carcinoma is present, there is no evidence on biopsy in the prostatic stroma of tumor invasion

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-1
  • WBC ≥ 4,000/mm^3
  • ANC ≥ 1,800/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 10.0 g/dL (transfusion or other intervention allowed)
  • Serum creatinine ≤ 1.5 mg/dL
  • Serum bilirubin ≤ 2.0 mg/dL
  • Glomerular filtration rate (GFR) > 25 mL/min (for patients receiving cisplatin, GFR > 60 mL/min)
  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Able to tolerate systemic chemotherapy combined with radiotherapy and a radical cystectomy (if necessary), in the opinions of the urologist, radiation oncologist, and medical oncologist
  • No prior or concurrent malignancy of any other site or histology (except for nonmelanomatous skin cancer, T1a prostate cancer, or carcinoma in situ of the uterine cervix) unless the patient has been disease-free for ≥ 5 years
  • No severe, active co-morbidity including any of the following:

    • Unstable angina and/or congestive heart failure that required hospitalization within the past 6 months
    • Transmural myocardial infarction that occurred within the past 6 months
    • Acute bacterial or fungal infection requiring IV antibiotics at the time of registration
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding any study therapy at the time of registration
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
    • AIDS based upon the current Centers for Disease Control definition (HIV testing not required)
  • No prior allergic reaction to cisplatin, mitomycin, or fluorouracil

PRIOR CONCURRENT THERAPY:

  • No prior systemic chemotherapy for bladder cancer
  • Prior chemotherapy for a different cancer allowed
  • No prior radiotherapy to the region of this cancer that would result in overlap of radiotherapy fields
  • No concurrent drugs that have potential nephrotoxicity or ototoxicity (e.g., aminoglycoside)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00981656

Locations
United States, Georgia
Emory Crawford Long Hospital Recruiting
Atlanta, Georgia, United States, 30308
Contact: Peter J. Rossi     404-686-4411        
Winship Cancer Institute of Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Clinical Trials Office - Winship Cancer Institute     404-778-1900        
United States, Maryland
St. Agnes Hospital Cancer Center Recruiting
Baltimore, Maryland, United States, 21229
Contact: Richard S. Hudes, MD     410-368-2965        
United States, Massachusetts
Hudner Oncology Center at Saint Anne's Hospital - Fall River Recruiting
Fall River, Massachusetts, United States, 02721
Contact: Clinical Trials Office - Hudner Oncology Center at Saint Anne'     508-674-5600 ext. 2019        
United States, New Hampshire
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center Recruiting
Lebanon, New Hampshire, United States, 03756-0002
Contact: Clinical Trials Office - Norris Cotton Cancer Center     603-650-7609     cancerhelp@dartmouth.edu    
United States, New York
Beth Israel Medical Center - Petrie Division Recruiting
New York, New York, United States, 10003-3803
Contact: Clinical Trials Office - Beth Israel Medical Center - Petrie D     212-844-6286        
United States, Ohio
Summa Center for Cancer Care at Akron City Hospital Recruiting
Akron, Ohio, United States, 44309-2090
Contact: Clinical Trials Office - Akron City Hospital     330-375-6101        
Barberton Citizens Hospital Recruiting
Barberton, Ohio, United States, 44203
Contact: William F. Demas, MD     330-375-3557        
Cancer Care Center, Incorporated Recruiting
Salem, Ohio, United States, 44460
Contact: William F. Demas, MD     330-375-3557        
Cancer Treatment Center Recruiting
Wooster, Ohio, United States, 44691
Contact: Clinical Trials Office - Cancer Treatment Center     330-375-4221        
United States, Pennsylvania
Fox Chase Cancer Center - Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19111-2497
Contact: Clinical Trials Office - Fox Chase Cancer Center - Philadelphi     215-728-4790        
United States, Texas
University of Texas Medical Branch Recruiting
Galveston, Texas, United States, 77555-0361
Contact: Clinical Trials Office - University of Texas Medical Branch     409-772-1950        
United States, Vermont
Norris Cotton Cancer Center - North Recruiting
Saint Johnsbury, Vermont, United States, 05819
Contact: Alan C. Hartford, MD, PhD     603-650-6600        
Sponsors and Collaborators
Radiation Therapy Oncology Group
Investigators
Study Chair: William U. Shipley, MD, FACR Massachusetts General Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Walter John Curran, Jr, Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00981656     History of Changes
Other Study ID Numbers: CDR0000654727, RTOG-0926
Study First Received: September 19, 2009
Last Updated: September 26, 2012
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage I bladder cancer
transitional cell carcinoma of the bladder

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Mitomycins
Mitomycin
Cisplatin
Fluorouracil
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Alkylating Agents
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on June 17, 2013