Fenretinide in Treating Patients With Biochemically Recurrent Hormone-Naïve Prostate Cancer
Condition: Adenocarcinoma of the Prostate; Recurrent Prostate Cancer
MeSH terms: Prostatic Neoplasms; Recurrence
Intervention: fenretinide; laboratory biomarker analysis
Intervention description: Given orally; Correlative studies
Intervention MeSH terms: Fenretinide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: Male
Healthy volunteers: No

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
    

Eligibility 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