Radiation Therapy and Chemotherapy in Treating Patients With Stage I Bladder Cancer
Condition: Bladder Cancer
MeSH terms: Urinary Bladder Neoplasms
Intervention: cisplatin; 5-fluorouracil; Mitomycin; Three-Dimensional Conformal Radiation Therapy
Intervention description: 60-minute intravenous (IV) infusion of 15 mg/m^2 on days 1, 2, 3, 15, 16, 17, 29, 30, and 31 of radiation treatment.; Continuous IV infusion of 500 mg/m^2/24 hrs for 5 consecutive days during weeks 1 and 4 of radiation treatment.; IV bolus dose of 12 mg/m^2 on day 1 of radiation treatment.; Total dose to the gross bladder volume of 61.2 Gy as 34 daily fractions 5 days/week, for approximately 7 weeks.
Intervention MeSH terms: Fluorouracil; Mitomycins; Mitomycin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 37.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: stage I bladder cancer; transitional cell carcinoma of the bladder

Summary:

      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.
    

Eligibility criteria:

        Inclusion criteria

          1. Pathologically proven diagnosis of carcinoma of the bladder within 105 days prior to
             registration.

             • Operable patients whose initial tumor is a 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 who have involvement of the prostatic urethra with urothelial
             carcinoma and have no evidence of stromal invasion of the prostate remain eligible. If
             the patient's initial tumor was a high grade stage Ta urothelial carcinoma then
             his/her recurrent tumor must be a high grade stage T1 urothelial carcinoma to be
             eligible.

          2. Patients must have a high grade urothelial carcinoma stage Ta or T1 that has recurred
             within 540 days after completion of the initial treatment [TURBT and intravesical
             Bacillus Calmette Guerin (BCG) immunotherapy] or on initial presentation with a T1
             high grade tumor, the participating urologist judged BCG therapy is contraindicated or
             unsuitable because the patient is found to be intolerant of BCG therapy or because
             this patient may be immuno-compromised in ways other than that mentioned in Exclusion
             Criteria 2.8 or because the patient refuses BCG therapy.

          3. With the presentations as described in Section 2, the participating urologist judges
             that the standard next therapy, based on present urologic guidelines for this patient,
             is radical cystectomy.

          4. If radiologic evaluation of a lymph node is interpreted as "positive", this must be
             evaluated further either by lymphadenectomy or by percutaneous needle biopsy. Patients
             with histologically or cytologically confirmed node metastases will not be eligible.

          5. Patients must have an adequately functioning bladder as judged by the participating
             urologist and radiation oncologist and have undergone a re-staging TURBT by the
             participating urologist that showed (or was present in the outside pathology specimen)
             a high grade stage Ta or T1 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.

          6. Patient must be considered able to tolerate systemic chemotherapy combined with pelvic
             radiation therapy, and a radical cystectomy (if necessary) by the joint agreement of
             the participating urologist, radiation oncologist, and medical oncologist.

          7. Appropriate stage for protocol entry, based upon the following minimum diagnostic
             workup within 60 days prior to registration:

             • History/physical examination including weight, performance data, body surface area

          8. Zubrod Performance Status ≤ 1

          9. Age ≥ 18

         10. Complete blood count (CBC)/differential obtained no more than 30 days prior to
             registration on study, with adequate bone marrow function defined as follows:

               -  White blood cell count (WBC) ≥ 4,000/ml

               -  Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3

               -  Platelets ≥ 100,000 cells/mm3

               -  Hemoglobin ≥ 10.0 g/dl (Note: The use of transfusion or other intervention to
                  achieve Hgb ≥ 10.0 g/dl is acceptable.)

         11. If the patient is to be treated with cisplatin, the serum creatinine should be ≤ 1.5
             mg%; serum bilirubin of ≤ 2.0 mg%

         12. Glomerular filtration rate (GFR) > 25 ml/min [For patients receiving cisplatin, GFR ≥
             60 ml/min]

         13. Serum pregnancy test for female patients of childbearing potential, ≤ 72 hours prior
             to study entry; women of childbearing potential and male participants must practice
             adequate contraception.

         14. Patient must be able to provide study-specific informed consent prior to study entry.

        Exclusion Criteria

          1. Evidence of tumor-related hydronephrosis

          2. Evidence of distant metastases or histologically or cytologically proven lymph node
             metastases

          3. Prior systemic chemotherapy for bladder cancer; prior chemotherapy for a different
             cancer is allowable

          4. A prior or concurrent malignancy of any other site or histology unless the patient has
             been disease-free for ≥ 5 years except for non-melanoma skin cancer and/or stage T1a
             prostate cancer or carcinoma in situ of the uterine cervix or a urothelial carcinoma
             of the upper urinary tract stage pTa, pTis or pT1 that has not been free of disease
             after treatment for more than a 2-year period

          5. Patients with pN+ or > T1 disease or who have not had a visibly complete TURBT

          6. Patients receiving any drugs that have potential nephrotoxicity or ototoxicity (such
             as an aminoglycoside)

          7. Prior radiotherapy to the region of the study cancer that would result in overlap of
             radiation therapy fields

          8. Severe, active co-morbidity, defined as follows:

               -  Unstable angina and/or congestive heart failure requiring hospitalization within
                  the last 6 months;

               -  Transmural myocardial infarction within the last 6 months;

               -  Acute bacterial or fungal infection requiring intravenous antibiotics at the time
                  of registration;

               -  Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
                  requiring hospitalization or precluding study therapy at the time of
                  registration;

               -  Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
                  note, however, that laboratory tests for liver function and coagulation
                  parameters are not required for entry into this protocol.

               -  Acquired Immune Deficiency Syndrome (AIDS) based upon the current Centers for
                  Disease Control and Prevention (CDC) definition; note, however, that HIV testing
                  is not required for entry into this protocol. The need to exclude patients with
                  AIDS from this protocol is necessary because the treatments involved in this
                  protocol may be significantly immunosuppressive. Protocol-specific requirements
                  may also exclude immuno-compromised patients.

          9. Pregnancy or women of childbearing potential and men who are sexually active and not
             willing/able to use medically acceptable forms of contraception; this exclusion is
             necessary because the treatment involved in this study may be significantly
             teratogenic.

         10. Prior allergic reaction to the study drugs (cisplatin, mitomycin, 5FU) involved in
             this