Fenretinide in Treating Patients With Biochemically Recurrent Hormone-Naïve Prostate Cancer

• Status: Completed
• Trial end date: 2009-01-01
• Target enrollment: 0
• Participant gender: Male

Summary

This phase II trial is studying how well fenretinide works in treating patients with biochemically (rising PSA level) recurrent hormone-naïve (no previous hormone therapy) prostate cancer. Drugs used in chemotherapy, such as fenretinide, work in different ways to stop tumor cells from dividing so they stop growing or die

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Fenretinide; Hormones

Criteria

Inclusion Criteria:

• Patient must have a histologically or cytologically confirmed history of adenocarcinoma of the prostate

• Patients must have a rising PSA, following a nadir value of < 4 ng/mL for patients treated with primary radiation and < 0.3 ng/mL for patients treated with radical prostatectomy, with no clinical or radiographic evidence of metastatic disease; the rising PSA must be confirmed by two consecutive increases, separated by at least 2 weeks; the absolute PSA value must be > 2.0 ng/mL, and the increment of increase must be at least 0.5 ng/mL above the nadir

• Following radical prostatectomy, patients can have received adjuvant radiation therapy for positive margins or pT3 disease; patients may also have received radiation therapy for local recurrence, provided that they subsequently have a rising PSA after a new PSA nadir of < 4ng/mL

• Bone scan negative for metastatic disease within 4 weeks prior to registration

• Patients must have a performance status of 0, 1, or 2

• The effects of fenretinide on fetal conception and development at the recommended therapeutic dose are unknown; for this reason, men enrolled in this trial must agree to use adequate contraception prior to study entry and for the duration of study participation

• Peripheral absolute neutrophil count (ANC) >= 1000/μL

• Platelet count >= 100,000/μL (transfusion independent; defined as: without transfusion for 3 weeks prior to obtaining study entry value)

• Hemoglobin >= 8.0 gm/dL (may receive RBC transfusions or exogenous erythropoietin)

• Life expectancy of greater than 3 months

• Serum creatinine =< 1.5 gm/dL

• Creatinine clearance or radioisotope GFR >= 50 ml/min/m2

• Total bilirubin =< 1.5 mg/dL

• SGOT (AST) and SGPT (ALT) < 2.5 x normal

• Patients with seizure disorders may be enrolled if on anticonvulsants and well controlled

• CNS toxicity =< Grade 2

• Patient must be able to consume the entire intact capsule(s) in the dosage prescribed for body surface area

• Triglycerides are less than 300mg/dl

• All patients will have malignancy confirmed by review of their biopsy specimens by the Division of Pathology of the City of Hope National Medical Center, the University of Southern California/LA County/Norris Comprehensive Cancer Center, or the University of California at Davis

• In patients who received radiotherapy, the absolute increase of PSA must be at least 2ng/ml to account for the "bounce" phenomenon

Exclusion Criteria:

• Patients with evidence of metastatic disease

• PSA progression not verified by sequential rising PSA as discussed in Eligibility section

• Inability to take oral fenretinide

• Patients who have had prior cytotoxic chemotherapy or androgen ablative therapy

• Patients with history of receiving, or current administration of, chemotherapeutic agents, biological response modifiers, or corticosteroids; patients are permitted to have received up to 9 months of neoadjuvant or adjuvant hormone ablation in conjunction with their primary definitive therapy; androgen deprivation must have been completed at least one year prior to registration; no complementary or alternative therapy (e.g. St. John's Wort, PC-SPES, or other herbal remedies taken for the purpose of treating prostate cancer) may be given during protocol treatment

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to fenretinide (i.e. retinoids)

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/ social situations that would limit compliance with study requirements

• No prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ carcinoma of any site, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years

• Patients should not take any drugs suspected of causing pseudotumor cerebri, which include tetracycline, nalidixic acid, nitrofurantoin, phenytoin, sulfonamides, lithium, amiodarone, or vitamin A

• Patients may have received one prior investigational anti-cancer agent

• HIV-positive patients receiving combination anti-retroviral therapy are excluded from this study because of possible pharmacokinetic interactions with fenretinide; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated

• Patients should not concurrently take medications that may potentially act as modulators of intracellular ceramide levels or ceramide cytotoxicity, sphingolipid transport, or p-glycoprotein (MDR1) or MRP1 drug/lipid transporters, such as: cyclosporine A or analogue; verapamil; tamoxifen or analogue; ketoconazole, chlorpromazine; RU486; indomethacin; or sulfinpyrazone

• Patients with known uncontrolled hypertriglyceridemia resulting in pancreatitis are excluded from study; patients with fasting triglycerides equal to or greater then 300mg/dl should start on medical treatment for hypertriglyceridemia (ex. fibrate derivatives); fenretinide will only be started when triglycerides are less than 300mg/dl

• Patients with known retinopathy from any source are excluded from the protocol as elevated ceramide levels from Fenretinide may exacerbate and/or lead to permanent retinal damage in this population

• Patients taking antioxidant supplements (vitamin C or E) must discontinue use before being eligible for protocol