Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

Radiation Therapy and Cisplatin or Mitomycin and Fluorouracil in Treating Patients with Non-Muscle Invasive Stage I Bladder Cancer

Protocol: RTOG-0926

Full 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

Purpose

This phase II trial studies how well radiation therapy when given together with cisplatin or mitomycin and fluorouracil prevents cancer from returning after surgery in patients with bladder cancer that has not invaded the bladder muscle but has not responded to standard treatment. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, mitomycin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving these chemotherapy drugs may make tumor cells more sensitive to radiation therapy.

Study Objective

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

I. To evaluate the rate of freedom from radical cystectomy at 5 years.

II. To evaluate the rate of freedom from the development of distant disease progression at 3 and 5 years.

III. Rate of freedom from progression of bladder tumor to stage T2 or greater at 3 and 5 years.

IV. To evaluate disease-specific survival and overall survival.

V. To evaluate the incidence of acute and late pelvic toxicity.

VI. To evaluate the efficacy of this treatment approach in preventing the recurrence of any local bladder tumor.

VII. To evaluate the potential value of tumor histopathology plus molecular genetic, deoxyribonucleic acid (DNA) content, and urine proteomics parameters as possible significant prognostic factors for tumor control with this treatment approach.

VIII. To collect American Urological Association (AUA) symptom scores at baseline and at 3 years.

OUTLINE:

Beginning within 15 weeks of transurethral resection of the bladder tumor, patients undergo 3-dimensional conformal radiotherapy (3D-CRT) once daily (QD) 5 days per week during weeks 1-7 (34 fractions). Patients also receive either cisplatin intravenously (IV) over 60 minutes on days 1-3, 15-17, and 29-31 OR mitomycin IV on day 1 of week 1 and fluorouracil IV continuously over 24 hours on days 1-5 of weeks 1 and 4. Treatment continues in the absence of unacceptable toxicity.

After completion of study treatment, patients are followed up at 8-10 weeks, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

Are you eligible?

Inclusion Criteria:

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

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 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 severe, active co-morbidity or because the patient refuses BCG therapy

The participating urologist judges that the standard next therapy, based on present urologic guidelines for this patient, is radical cystectomy

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

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

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

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

Zubrod performance status =< 1

White blood cell count (WBC) >= 4,000/ml

Absolute neutrophil count (ANC) >= 1,800 cells/mm^3

Platelets >= 100,000 cells/mm^3

Hemoglobin >= 10.0 g/dL (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 10.0 g/dl is acceptable)

If the patient is to be treated with cisplatin, the serum creatinine should be =< 1.5 mg%

If the patient is to be treated with cisplatin, the serum bilirubin of =< 2.0 mg%

Glomerular filtration rate (GFR) > 25 ml/min (for patients receiving cisplatin, GFR >= 60 ml/min)

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

Patient must be able to provide study-specific informed consent prior to study entry

Exclusion Criteria:

Evidence of tumor-related hydronephrosis

Evidence of distant metastases or histologically or cytologically proven lymph node metastases

Prior systemic chemotherapy for bladder cancer; prior chemotherapy for a different cancer is allowable

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

Patients with pN+ or > T1 disease or who have not had a visibly complete TURBT

Patients receiving any drugs that have potential nephrotoxicity or ototoxicity (such as an aminoglycoside)

Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields

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 human immunodeficiency virus (HIV) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immuno-compromised patients

Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception

Prior allergic reaction to the study drugs (cisplatin, mitomycin, fluorouracil [5FU]) involved in this protocol

Bladder Cancer Genitourinary Cancers