RATIONALE: Drugs used in chemotherapy, such as fenretinide, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: 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.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the prostate recurrent prostate cancer stage II prostate cancer stage III prostate cancer	Drug: fenretinide  Procedure: chemotherapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the prostate-specific antigen (PSA) response in patients with biochemically recurrent, hormone-naïve prostate cancer treated with fenretinide.
• Determine the PSA doubling time and time to PSA progression in patients treated with this drug.
• Determine the qualitative and quantitative toxic effects of this drug in these patients.
• Determine the bioavailability of this drug in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to prior therapy (surgery vs radiotherapy and/or brachytherapy vs both), stage at diagnosis (organ confined vs extra-capsular extension vs lymph node positive), Gleason score at diagnosis (2-4 vs 5-6 vs 7-10), and prostate-specific antigen level at diagnosis (0-4 ng/mL vs 4.1-10 ng/mL vs > 10 ng/mL).

Patients receive oral fenretinide twice daily on days 1-7. Courses repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 12-37 patients will be accrued for this study.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the prostate
• Rising prostate-specific antigen (PSA) (absolute PSA value > 2.0 ng/mL above the nadir) after a nadir (< 4 ng/mL for post-radiotherapy patients and 0.3 ng/mL for post-prostatectomy patients) after local curative therapy (radical prostatectomy and/or pelvic irradiation)
• Confirmed by 2 sequential PSA increases of at least 0.5 ng/mL each, taken ≥ 2 weeks apart
• No clinical or radiographic evidence of metastatic or locally recurrent disease
• CT scan or MRI of the chest/abdomen/pelvis AND bone scan negative for metastatic disease within the past 4 weeks

PATIENT CHARACTERISTICS: Age

• Not specified

Performance status

• ECOG 0-2

Life expectancy

• More than 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3 (transfusion independent)
• Hemoglobin ≥ 8.0 g/dL (transfusion or exogenous epoetin alfa allowed)
• WBC ≥ 3,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 mg/dL
• AST and ALT < 2.5 times upper limit of normal

Renal

• Creatinine normal OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Fertile patients must use effective contraception during and for at least 3 months after study participation
• Able to swallow entire intact capsules
• No prior allergic reaction attributed to compounds of similar chemical or biological composition to study drug
• No CNS toxicity grade 3 or greater
• No uncontrolled seizure disorder
• Seizure disorders are allowed provided patient is on anticonvulsants and disorder is well controlled
• No other concurrent uncontrolled illness
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ, or adequately treated stage I or II cancer currently in complete remission
• No known retinopathy
• No known uncontrolled hypertriglyceridemia resulting in pancreatitis
• Triglycerides < 300 mg/dL

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior or concurrent biological response modifiers for recurrent prostate cancer

Chemotherapy

• No prior cytotoxic chemotherapy
• No prior chemotherapy for recurrent prostate cancer
• No other concurrent anticancer chemotherapy

Endocrine therapy

• Prior neoadjuvant hormone ablation no longer than 4 months in duration allowed
• Prior neoadjuvant or adjuvant hormone ablation therapy allowed provided it was administered in conjunction with primary definitive therapy ≤ 9 months in duration
• No prior androgen ablative therapy
• No prior or concurrent corticosteroids for recurrent prostate cancer
• No prior or concurrent hormonal therapy for recurrent prostate cancer
• At least 1 year since prior androgen deprivation
• No concurrent tamoxifen
• No concurrent hormone ablative agents (including steroids)

Radiotherapy

• See Disease Characteristics
• Prior adjuvant radiotherapy for positive margins or pT3 disease allowed
• Prior radiotherapy allowed for local recurrence provided the patient has had a subsequent rise in PSA level from a nadir of < 4 ng/mL
• No concurrent radiotherapy for persistent PSA or for local recurrence
• No concurrent radiotherapy for recurrent prostate cancer

Surgery

• See Disease Characteristics

Other

• No more than 1 prior investigational anticancer agent
• No concurrent complementary or alternative therapy (e.g., Hypericum perforatum [St. John’s wort], PC-SPES, or any other herbal remedies) for prostate cancer
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent drugs suspected of causing pseudotumor cerebri (e.g., tetracycline, nalidixic acid, nitrofurantoin, phenytoin, sulfonamides, lithium, amiodarone, or vitamin A)
• No concurrent drugs that modulate intracellular ceramide levels, ceramide cytotoxicity, sphingolipid transport, or p-glycoprotein or multidrug resistance-associated protein-1 drug/lipid transporters (e.g., cyclosporine, verapamil, ketoconazole, chlorpromazine, mifepristone, indomethacin, or sulfinpyrazone)
• No concurrent antioxidant supplements (e.g., ascorbic acid or vitamin E)
• No concurrent participation in another therapeutic clinical trial

California
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States; Recruiting
      Tower Cancer Research Foundation, Beverly Hills,  California,  90211,  United States; Recruiting
      University of California Davis Cancer Center, Sacramento,  California,  95817,  United States; Recruiting
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033-0804,  United States; Recruiting
Pennsylvania
      Hillman Cancer Center at University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15232,  United States; Recruiting

Study chairs or principal investigators

Jacek Pinski, MD,  Study Chair,  University of Southern California   

Study ID Numbers:  CDR0000357312; CCC-PHII-47; NCI-6168; NCT00080899
Record last reviewed:  February 2005
Last Updated:  April 5, 2005
Record first received:  April 7, 2004
ClinicalTrials.gov Identifier:  NCT00080899
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08