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A Phase II Trial of Fenretinide (4-HPR) in Biochemically Recurrent, Hormone Naive Prostate Cancer

Phase 2
Not Enrolling
Adenocarcinoma of the Prostate, Recurrent Prostate Cancer

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Trial Information

A Phase II Trial of Fenretinide (4-HPR) in Biochemically Recurrent, Hormone Naive Prostate Cancer


I. To assess the PSA response in prostate cancer patients with only biochemical recurrence
after local curative therapy who are then treated with fenretinide (4-HPR).

II. To assess PSA doubling time as a measure of disease activity, time to PSA progression in
prostate cancer patients receiving fenretinide.

III. To evaluate the qualitative and quantitative toxicities of this agent in this patient

IV. To evaluate pharmacokinetic studies on the bioavailability of 4-HPR in this patient

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.

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

- 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

- 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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Anti-tumor activity in terms of change in PSA levels

Outcome Time Frame:

Baseline to 5 years

Safety Issue:


Principal Investigator

Jacek Pinski

Investigator Role:

Principal Investigator

Investigator Affiliation:

Beckman Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

June 2004

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Prostate
  • Recurrent Prostate Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Prostatic Neoplasms



City of Hope Medical Center Duarte, California  91010