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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Radiation Therapy Oncology Group
Sponsor:
Collaborators:
NRG Oncology Foundation, Inc.
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00981656
First received: September 19, 2009
Last updated: July 10, 2014
Last verified: July 2014
  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: Intervention Model: Single Group Assignment
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 Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Rate of freedom from radical cystectomy at 3 years [ Time Frame: Three years from the date of registration. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Rate of freedom from radical cystectomy at 5 years [ Time Frame: Five years from the date of registration. ] [ Designated as safety issue: No ]
  • Rate of freedom from the development of distant disease progression at 3 and 5 years [ Time Frame: From the date of registration to the date of first appearance of disease in a non-regional lymph node, solid organ or bone within 3 years and 5 years after registration. ] [ Designated as safety issue: No ]
  • Rate of freedom from progression of bladder tumor to stage T2 or greater at 3 and 5 years [ Time Frame: From the date of registration to the date of first documented increase of 50% or more in the largest diameter of the endoscopically appreciable tumor or the progression from stage T1 to stage T2 or beyond within 3 years and 5years afeter registration. ] [ Designated as safety issue: No ]
  • Disease-specific survival at 5 years [ Time Frame: From the date of registration to the date of death due to bladder cancer. ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: From the date of registration to the date of death due to any cause. ] [ Designated as safety issue: No ]
  • Incidence of adverse events as assessed by Common Toxicity Criteria for Adverse Effects (CTCAE), v3.0 [ Time Frame: From the date of registration to the date of Grade 3 or more adverse events based on the active version of CTCAE among all eligible patients. ] [ Designated as safety issue: Yes ]
  • Recurrence rate of any local bladder tumor [ Time Frame: From the date of registration to the date of first documented local bladder recurrence. ] [ Designated as safety issue: No ]
  • Descriptive analysis for American Urological Association symptom score at baseline and at 3 years [ Time Frame: From the date of registration to 3 years after registration. ] [ 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: TURBT + Concurrent RT + Chemotherapy
Transurethral resection of the bladder tumor (TURBT) + Concurrent Radiation Therapy (RT) + Chemotherapy
Drug: cisplatin
Given IV
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:

  • Pathologically (histologically or cytologically) diagnosis of carcinoma of the bladder within 70 days prior to registration.

    • Patients with operable tumors that are primary high grade urothelial carcinoma of the bladder exhibiting histologic evidence of invasion into the lamina propria (disease clinical stage T1) or a high grade stage Ta urothelial carcinoma without hydronephrosis.
    • Patients with disease involvement of the prostatic urethra with urothelial carcinoma and have no evidence of stromal invasion of the prostate. If the patient's initial tumor was a high grade Ta urothelial carcinoma then his/her recurrent tumor must be a high grade stage T1 urothelial carcinoma to be eligible.
    • Patients must have a high grade urothelial carcinoma stage Ta or T1 that has recurred within 540 days after completion of the initial treatment (transurethral resection bladder tumor [TURBT] and intravesical bacillus Calmette-Guerin [BCG] immunotherapy) or have presented to a participating urologist who judged BCG therapy is contraindicated because this patient may be immuno-compromised or because the patients refuses BCG therapy
  • 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
  • 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
  • White blood cell count (WBC) ≥ 4,000/mm^3
  • Absolute neutrophil count (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 5-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
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: 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
NRG Oncology Foundation, Inc.
Investigators
Principal Investigator: William U. Shipley, MD, FACR Massachusetts General Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00981656     History of Changes
Other Study ID Numbers: RTOG 0926, CDR0000654727
Study First Received: September 19, 2009
Last Updated: July 10, 2014
Health Authority: United States: Federal Government

Keywords provided by Radiation Therapy Oncology Group:
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 July 26, 2014