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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00026091
First received: November 9, 2001
Last updated: March 22, 2013
Last verified: February 2013
  Purpose

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


Condition Intervention Phase
Recurrent Ovarian Epithelial Cancer
Recurrent Primary Peritoneal Cavity Cancer
Stage IV Ovarian Epithelial Cancer
Stage IV Primary Peritoneal Cavity Cancer
Drug: fenretinide
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Fenretinide (NSC 374551) in Recurrent Ovarian Cancer and Primary Peritoneal Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rate (CR or PR) [ Time Frame: Up to 9 years ] [ Designated as safety issue: No ]
    Associated exact 95% confidence intervals will be calculated.


Secondary Outcome Measures:
  • Time to treatment failure [ Time Frame: up to 9 years ] [ Designated as safety issue: No ]
    Estimated using the product-limit method of Kaplan and Meier.

  • Duration of response [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Estimated using the product-limit method of Kaplan and Meier.

  • Overall survival [ Time Frame: From first day of treatment to time of death due to any cause, assessed up to 9 years ] [ Designated as safety issue: No ]
    Estimated using the product-limit method of Kaplan and Meier.

  • Toxicity [ Time Frame: Up to 9 years after completion of treatment ] [ Designated as safety issue: Yes ]
    Tables will be constructed to summarize the observed incidence by severity and type of toxicity.

  • Pharmacokinetics of fenretinide [ Time Frame: Baseline. day 1, 4 and 7 of courses 1, day 1 of courses 2, 5, and 9, day 7 of courses 4 and 8 ] [ Designated as safety issue: No ]
    Summarized with simple summary statistics: means or medians, ranges, and standard deviations (if numbers and distribution permit).

  • Molecular change [ Time Frame: Baseline to end of treatment ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: September 2001
Primary Completion Date: March 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (fenretinide)
Patients receive oral fenretinide twice daily on days 1-7. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: fenretinide
Given orally
Other Names:
  • fenretinimide
  • McN-R-1967
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed 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.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00026091

Locations
United States, California
University of Southern California
Los Angeles, California, United States, 90033-0804
Sponsors and Collaborators
Investigators
Principal Investigator: Agustin Garcia University of Southern California
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00026091     History of Changes
Other Study ID Numbers: NCI-2013-00457, PHII-25, N01CM17101, CDR0000068985
Study First Received: November 9, 2001
Last Updated: March 22, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Peritoneal Neoplasms
Abdominal Neoplasms
Adnexal Diseases
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Ovarian Diseases
Peritoneal Diseases
Urogenital Neoplasms

ClinicalTrials.gov processed this record on October 23, 2014