Fenretinide/LXS Oral Powder Plus Ketoconazole in Recurrent Ovarian Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine the effectiveness of fenretinide (4-HPR/LXS) plus ketoconazole in the treatment of recurrent ovarian cancer or primary peritoneal carcinoma. In addition, researchers would like to determine if the drugs are most effective together or if fenretinide (4-HPR/LXS) is most effective alone.

Detailed Description
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In this study, an initial Phase I component of six patients will be conducted to monitor for potential toxicities as this wil be the initial adult experience of fenretinide (4-HPR) given together with ketoconazole

Official Title
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Phase I/II Trial of Fenretinide/LXS Oral Powder (NSC 374551) Plus Ketoconazole in Recurrent Ovarian Cancer and Primary Peritoneal Carcinoma

Conditions
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Ovarian Cancer, Cancer of Ovary, Cancer of the Ovary, Ovary Neoplasms, Primary Peritoneal Carcinoma

Intervention / Treatment
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* Drug: Fenretinide/LXS + Ketoconazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recurrent epithelial ovarian cancer or primary peritoneal carcinoma that can be platinum sensitive or platinum resistant SWOG Performance Status 0-2 Previously received a platinum and paclitaxel containing regimen Projected Life Expectancy of at least 3 months Adequate bone marrow function Adequate organ function Must have received at least 1 prior salvage regimen for recurrent ovarian cancer Recovery from acute toxicities from surgery, radiation or chemotherapy At least 3 weeks from last therapy Exclusion Criteria: Prior fenretinide oral capsule use allowed. If prior IV fenretinide use, must contact study chair for eligibility Second malignancy within last 5 years Use of concomitant antioxidants, such as vitamin C or E Untreated or symptomatic brain metastases History of hypertriglyceride levels > 200 mg/dl; triglyceride levels < 200 and receiving treatment are okay. Use of certain medications is prohibited - contact study coordinator for information

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fenretinide/LXS + Ketoconozale<br>One course is defined as 7 days of Fenretinide/LXS + Ketoconazole followed by 14 days of rest. A course is repeated every 21 days if no evidence of disease progression for six courses. | Drug: Fenretinide/LXS + Ketoconazole<br>* Starting dose is: Fenretinide/LXS 800 mg 4-HPR/m2/day and Ketoconazole 400 mg/day<br>* Other names: Feoris;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 2: Progression Free Survival | The objective response rate will be calculated as the percent of evaluable patients whose best response is a CR or PR, and assoicated exact 95% confidence intervals will be calculated. Time to treatment failure, duration of response and survival will be estimated using the product-limit method of Kaplan and Meier. | From date of enrollment until date of documented progression or date of death (up to 48 months after last patient enters treatment) | 
| Phase 2: Overall Survival | The objective response rate will be calculated as the percent of evaluable patients whose best response is a CR or PR, and assoicated exact 95% confidence intervals will be calculated. Time to treatment failure, duration of response and survival will be estimated using the product-limit method of Kaplan and Meier. | From enrollment up to first date of progressive disease or death from any cause (up to 48 months after last patient entered treatment) | 
| Phase 1: To determine the systemic toxicity profile of 4-HPR/LXS oral powder + ketoconazole | Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen. | From time of first dose to the last (average 6 months) | 
| Phase 2: Event Free Survival | The objective response rate will be calculated as the percent of evaluable patients whose best response is a CR or PR, and assoicated exact 95% confidence intervals will be calculated. Time to treatment failure, duration of response and survival will be estimated using the product-limit method of Kaplan and Meier. | From enrollment up to the first date of progressive disease or death from any cause (up to 48 months after last patient entered on treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics - | Area under the plasma concentration versus time curve (AUC) steady state plasma concentrations; drug levels in plasma | up to 48 months after the last subject enrolled | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chemotherapy