Fenretinide in Treating Patients Who Have Undergone Surgery for Bladder Cancer

M.D. Anderson Cancer Center

Status and phase

Completed

Phase 3

Conditions

Bladder Cancer

Treatments

Drug: Fenretinide

Other: Placebo

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00004154

ID95-236 (Other Identifier)

CDR0000067387

MDA-ID-95236

NCI-T98-0051

NCI-G99-1621

Details and patient eligibility

About

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.

Full description

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.

Enrollment

111 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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