Sponsored by National Cancer Institute (NCI)

Phase	Quota	Distance
Phase 2		Near

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, 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 cisplatin works in treating patients with stage I bladder cancer.

Study Start Date: November 2009

Estimated Completion Date: October 2018

Specialties: Urology: Bladder,Oncology Oncology: Pharmacology/Therapy,Radiation Oncology,Renal/Urologic

Interventions

• Drug: cisplatin
• Drug: fluorouracil
• Drug: mitomycin C
• Radiation: 3-dimensional conformal radiation therapy

Inclusion 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 American Joint Committee on Cancer (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 bacillus Callamette-Guerin (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
• 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 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)

Exclusion criteria

Study Locations And Contact Information

• Emory Crawford Long Hospital, Atlanta Georgia
  Contact: Peter J Rossi 404-686-4411
• Winship Cancer Institute of Emory University, Atlanta Georgia
  Contact: Clinical Trials Office Winship Cancer Institute 404-778-1900
• St Agnes Hospital Cancer Center, Baltimore Maryland
  Contact: Richard S Hudes MD 410-368-2965
• Hudner Oncology Center at Saint Annes Hospital Fall River, Fall River Massachusetts
  Contact: Clinical Trials Office Hudner Oncology Center at Saint Anne 508-674-5600
• Norris Cotton Cancer Center at DartmouthHitchcock Medical Center, Lebanon New Hampshire
  Contact: Clinical Trials Office Norris Cotton Cancer Center 603-650-7609 cancerhelp@dartmouth.edu
• Beth Israel Medical Center Petrie Division, New York New York
  Contact: Clinical Trials Office Beth Israel Medical Center Petrie D 212-844-6286
• Summa Center for Cancer Care at Akron City Hospital, Akron Ohio
  Contact: Clinical Trials Office Akron City Hospital 330-375-6101
• Barberton Citizens Hospital, Barberton Ohio
  Contact: William F Demas MD 330-375-3557
• Cancer Care Center Incorporated, Salem Ohio
  Contact: William F Demas MD 330-375-3557
• Cancer Treatment Center, Wooster Ohio
  Contact: Clinical Trials Office Cancer Treatment Center 330-375-4221
• Fox Chase Cancer Center Philadelphia, Philadelphia Pennsylvania
  Contact: Clinical Trials Office Fox Chase Cancer Center Philadelphi 215-728-4790
• University of Texas Medical Branch, Galveston Texas
  Contact: Clinical Trials Office University of Texas Medical Branch 409-772-1950
• Norris Cotton Cancer Center North, Saint Johnsbury Vermont
  Contact: Alan C Hartford MD PhD 603-650-6600