Fenretinide in Treating Patients With Recurrent or Metastatic Ovarian Epithelial or Primary Peritoneal Cancer

Recurrent Ovarian Epithelial Cancer Clinical Trial

Official title:

Phase II Trial of Fenretinide (NSC 374551) in Recurrent Ovarian Cancer and Primary Peritoneal Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00026091
• Other study ID #: NCI-2013-00457
• Secondary ID: PHII-25N01CM1710
• Status: Completed
• Phase: Phase 2
• First received: November 9, 2001
• Last updated: March 22, 2013
• Start date: September 2001

Study information

• Verified date: February 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Phase II trial to study the effectiveness of fenretinide in treating patients who have recurrent or metastatic ovarian epithelial or primary peritoneal cancer. 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

Description:

PRIMARY OBJECTIVES:

I. To evaluate the efficacy of fenretinide (4-HPR) in patients with recurrent ovarian cancer or primary peritoneal carcinoma.

II. To assess the toxicity of this agent in this patient population. III. To evaluate molecular changes in normal and tumor cells induced by 4-HPR by studying: (a) the analysis of ceramide and glucosyleceramide levels before and after therapy, (b) intracellular levels of 4-HPR and 4-MPR, and (c) determinants of apoptosis (p53, p21, bcl-2, bax and terminal deoxynucleotidyl transferase [TdT] assay) in baseline tumor specimens, serial serum and tumor biopsy specimens where available, and surrogate in-vitro studies.

IV. To evaluate the pharmacokinetics of fenretinide. V. To further investigate the antiangiogenesis effects of fenretinide in in-vitro assays using ovarian cancer cell lines and in vascular growth factor (VEGF, TGFb) plasma levels in patients.

OUTLINE:

Patients receive oral fenretinide twice daily on days 1-7. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. primary completion date: March 2004
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Patients with histologically confirmed recurrent or metastatic epithelial ovarian cancer or primary peritoneal carcinoma

• Unidimensionally measurable disease; indicator lesions must not have been irradiated unless they have grown following radiation therapy

• SWOG performance status 0-2

• Patients must have received a platinum and paclitaxel containing regimen

• Patients are allowed to receive =< 2 prior chemotherapy regimens for recurrent disease; patients who are rechallenged with the same chemotherapy regimen are considered to have had that regimen only once

• Projected life expectancy must be at least 3 months

• Signed informed consent

• Absolute neutrophil count >= 1500/ul

• Platelet count >= 100,000 ul

• Bilirubin =< 2 times the institutional limit of normal

• ALT or AST =< 3 times the upper limit of normal

• Measured or calculated creatinine clearance >= 60 ml/min

• Fasting triglycerides =< 1 time the upper limit of normal; triglycerides may be "normalized" prior to study entry with use of an antilipemic agent (atorvastatin, fenofibrate)

• Patients must have recovered from acute toxicities from surgery, radiation or chemotherapy; at least 3 weeks will have elapsed since any prior therapy directed at the malignant tumor

• Patients of childbearing potential must agree to use an approved method of birth control

Exclusion Criteria:

• Prior fenretinide is not allowed; prior 13-cis, 9-cis or all-transretinoic acid are allowed

• Patients with a second malignancy within the last 5 years are not allowed, except for those with non-melanomatous skin cancer and carcinoma-in-situ of the cervix; all prior invasive malignancies must be in complete remission

• The use of concomitant antioxidants, such as vitamin C or E, is not allowed

• Patients with concurrent medical, psychological or social conditions of such severity that the investigator deems it unwise to enter the patient on protocol

• Untreated or symptomatic brain metastases

• Pregnant or nursing women

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasms, Glandular and Epithelial
• Ovarian Neoplasms
• Peritoneal Neoplasms
• Recurrent Ovarian Epithelial Cancer
• Recurrent Primary Peritoneal Cavity Cancer
• Stage IV Ovarian Epithelial Cancer
• Stage IV Primary Peritoneal Cavity Cancer

Intervention

Drug:
• fenretinide
Given orally

Other:
• laboratory biomarker analysis
Correlative studies
• pharmacological study
Correlative studies

Locations

Country	Name	City	State
United States	University of Southern California	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate (CR or PR)	Associated exact 95% confidence intervals will be calculated.	Up to 9 years	No
Secondary	Time to treatment failure	Estimated using the product-limit method of Kaplan and Meier.	up to 9 years	No
Secondary	Duration of response	Estimated using the product-limit method of Kaplan and Meier.	From the time measurement criteria met for CR/PR until the first date that recurrent or progressive disease is objectively documented, assessed up to 9 years	No
Secondary	Overall survival	Estimated using the product-limit method of Kaplan and Meier.	From first day of treatment to time of death due to any cause, assessed up to 9 years	No
Secondary	Toxicity	Tables will be constructed to summarize the observed incidence by severity and type of toxicity.	Up to 9 years after completion of treatment	Yes
Secondary	Pharmacokinetics of fenretinide	Summarized with simple summary statistics: means or medians, ranges, and standard deviations (if numbers and distribution permit).	Baseline. day 1, 4 and 7 of courses 1, day 1 of courses 2, 5, and 9, day 7 of courses 4 and 8	No
Secondary	Molecular change		Baseline to end of treatment	No