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Fenretinide in Treating Patients Who Have Undergone Surgery for Bladder Cancer

Primary Purpose

Bladder Cancer

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Fenretinide
Placebo
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bladder Cancer focused on measuring stage 0 bladder cancer, stage I bladder cancer, transitional cell carcinoma of the bladder

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Texas - MD Anderson Cancer Center
  • Baylor College of Medicine
  • Veterans Affairs Medical Center - Seattle

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Fenretinide

Placebo

Arm Description

Fenretinide (4-HPR) 200 mg orally every day for 12 months taken 25 out of every 28 days.

Placebo orally every day for 12 months, taken 25 out of every 28 days.

Outcomes

Primary Outcome Measures

Recurrence rate of transitional cell carcinoma (TCC)
Recurrence rates is defined as proportion of participants who recur within one year of surgery.

Secondary Outcome Measures

Full Information

First Posted
December 10, 1999
Last Updated
November 7, 2018
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00004154
Brief Title
Fenretinide in Treating Patients Who Have Undergone Surgery for Bladder Cancer
Official Title
Randomized Chemoprevention Trial With 4-HPR (Fenretinide) in Superficial Bladder Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
November 2018
Overall Recruitment Status
Completed
Study Start Date
July 30, 1998 (Actual)
Primary Completion Date
March 1, 2005 (Actual)
Study Completion Date
March 1, 2005 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Cancer
Keywords
stage 0 bladder cancer, stage I bladder cancer, transitional cell carcinoma of the bladder

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
111 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Fenretinide
Arm Type
Experimental
Arm Description
Fenretinide (4-HPR) 200 mg orally every day for 12 months taken 25 out of every 28 days.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo orally every day for 12 months, taken 25 out of every 28 days.
Intervention Type
Drug
Intervention Name(s)
Fenretinide
Other Intervention Name(s)
4-HPR
Intervention Description
200 mg/day (two 100 mg capsules) for 25 days of 28 day cycle.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Two placebo capsules for 25 days of 28 day cycle.
Primary Outcome Measure Information:
Title
Recurrence rate of transitional cell carcinoma (TCC)
Description
Recurrence rates is defined as proportion of participants who recur within one year of surgery.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anita L. Sabichi, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
University of Texas - MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Veterans Affairs Medical Center - Seattle
City
Seattle
State/Province
Washington
ZIP/Postal Code
98108
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
18172274
Citation
Sabichi AL, Lerner SP, Atkinson EN, Grossman HB, Caraway NP, Dinney CP, Penson DF, Matin S, Kamat A, Pisters LL, Lin DW, Katz RL, Brenner DE, Hemstreet GP 3rd, Wargo M, Bleyer A, Sanders WH, Clifford JL, Parnes HL, Lippman SM. Phase III prevention trial of fenretinide in patients with resected non-muscle-invasive bladder cancer. Clin Cancer Res. 2008 Jan 1;14(1):224-9. doi: 10.1158/1078-0432.CCR-07-0733.
Results Reference
result

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Fenretinide in Treating Patients Who Have Undergone Surgery for Bladder Cancer

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