Fenretinide in Treating Patients Who Have Undergone Surgery for Bladder Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as fenretinide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether fenretinide is more effective than a placebo in preventing the recurrence of bladder cancer after surgery to remove the tumor. PURPOSE: This randomized phase III trial is studying fenretinide to see how well it works compared to a placebo in treating patients who are at risk for recurrent bladder cancer following surgery to remove the tumor.

Detailed Description
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OBJECTIVES: Determine the efficacy, mechanism of action, and toxicity of fenretinide in patients at risk of recurrent superficial bladder cancer after complete resection of initial tumor. Determine the treatment effects in modulating the expression of retinoid receptors, chromosomal abnormalities (numerical chromosomal abnormalities and DNA ploidy), apoptosis, and autocrine motility factor receptor (intermediate endpoint markers of recurrent disease) in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to lesion type (multifocal vs solitary). Patients are randomized to one of two treatment arms. Patients receive either oral fenretinide or placebo on days 1-25. Courses repeat every 28 days for up to 1 year in the absence of disease progression, unacceptable toxicity, or development of a second primary cancer requiring therapy. Patients are followed every 3 months for 15 months. PROJECTED ACCRUAL: A total of 178 patients (89 per arm) will be accrued for this study.

Official Title
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Randomized Chemoprevention Trial With 4-HPR (Fenretinide) in Superficial Bladder Cancer

Conditions
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Bladder Cancer

Intervention / Treatment
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* Drug: Fenretinide
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven solitary or multifocal superficial (stage Ta, grades 1-2) transitional cell carcinoma (TCC) of the bladder meeting 1 of the following criteria: Newly diagnosed and no more than 4 weeks since resection Secondary after being tumor free (including carcinoma in situ) for more than 12 months with no intravesical therapy within that 12 months OR Histologically proven Ta, T1, or Tis TCC of the bladder previously treated with Bacillus Calmette-Guerin (BCG). Must have received 6 weeks of induction BCG followed by no evidence of disease by cystoscopy and cytology and then further treatment with 3 weekly doses of BCG. Visible tumor totally resected within 4 weeks prior to study entry and no further surgery, intravesical therapy, or systemic therapy planned No prostatic, prostatic urethral, or upper tract TCC involvement by the index tumor at resection No metastatic disease PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Zubrod (Eastern Cooperative Oncology Group (ECOG)) 0-2 Life expectancy: At least 2 years Hematopoietic: white blood count (WBC) greater than 3,000/mm^3 Platelet count greater than 100,000/mm^3 Hemoglobin greater than 11.0 g/dL Hepatic: serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) less than 1.5 times upper limit of normal (ULN) Renal: Creatinine less than 2.0 mg/dL Other: Triglyceride level less than 2.5 times ULN No other concurrent malignancy except nonmelanomatous skin cancer No other malignancy within the past 5 years unless currently disease free, at least 6 months since prior therapy, no current or planned active therapy, and expected disease-free survival at least 2 years Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 1 year after the study participation PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics No concurrent systemic biologic therapy Chemotherapy: See Disease Characteristics No prior systemic cytotoxic chemotherapy for bladder cancer At least 1 year since prior cytotoxic chemotherapy for nonbladder cancer No concurrent systemic chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy to the bladder No concurrent radiotherapy Surgery: See Disease Characteristics Other: At least 3 months since prior high-dose vitamin A (greater than 25,000 IU) or beta carotene (at least 30 mg/day) At least 3 months since prior retinoid therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fenretinide<br>Fenretinide (4-HPR) 200 mg orally every day for 12 months taken 25 out of every 28 days. | Drug: Fenretinide<br>* 200 mg/day (two 100 mg capsules) for 25 days of 28 day cycle.<br>* Other names: 4-HPR;|
| Placebo Comparator: Placebo<br>Placebo orally every day for 12 months, taken 25 out of every 28 days. | Other: Placebo<br>* Two placebo capsules for 25 days of 28 day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence rate of transitional cell carcinoma (TCC) | Recurrence rates is defined as proportion of participants who recur within one year of surgery. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage 0 bladder cancer, stage I bladder cancer, transitional cell carcinoma of the bladder