Perifosine in Treating Patients With Recurrent Prostate Cancer

Phase 2

Terminated

Conditions: Recurrent Prostate Cancer
Stage IIB Prostate Cancer
Stage III Prostate Cancer
Stage IV Prostate Cancer
Adenocarcinoma of the Prostate

Interventions: Drug: perifosine
Other: laboratory biomarker analysis

Registration Number: NCT00058214

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: Phase II trial to study the effectiveness of perifosine in treating patients who have recurrent prostate cancer. Drugs used in chemotherapy such as perifosine use different ways to stop tumor cells from dividing so they stop growing or die

Detailed Description: PRIMARY OBJECTIVES:

I. To assess the PSA response in prostate cancer patients with only biochemical recurrence after local curative therapy who are then treated with perifosine.

II. To assess the secondary endpoints of a) six-month increase in PSA levels compared to baseline, b) PSA doubling time and c) time to PSA progression in prostate cancer patients receiving perifosine.

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

IV. To investigate potential molecular markers predictive of decreased PSADT and possibly PSA response in prostate cancer patients receiving perifosine.

OUTLINE: This is a multicenter study. Patients are stratified according to prior therapy (surgery vs radiotherapy with or without brachytherapy vs surgery and radiotherapy) and original combined Gleason score (7 or less vs 8-10).

Patients receive oral perifosine once daily on days 1-28. On day 1 of course 1 only, patients receive 2 doses of oral perifosine. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease by PSA alone may receive up to 3 additional courses of therapy after documentation of progression.

Recruitment & Eligibility

Status: TERMINATED

Sex: Male

Target Recruitment: 25

Inclusion Criteria

Patients must have histologically or cytologically confirmed adenocarcinoma of the prostate
Patients must have a rising PSA >= 2.0 following a nadir after local curative therapy (either radical prostatectomy and/or pelvic radiation) with no clinical or radiographic evidence of metastatic disease; PSA >= 2.0 elevation must be confirmed by two consecutive increases, each measured at least 2 weeks apart; only patients with a biochemical (PSA) recurrence with no physical exam or radiographic evidence of local or distant relapse are eligible
Prior hormonal therapy in the form of neoadjuvant or adjuvant therapy is allowed as long as neither lasted for more than 9 months; androgen deprivation therapy must have been completed at least one year prior to registration; patients could not have had a rising PSA at the time that neoadjuvant or adjuvant therapy was stopped
Life expectancy of greater than 3 months
Karnofsky performance status > 60%
Leukocytes >= 3,000/uL
Absolute neutrophil count >= 1,500/uL
Platelets >= 100,00/uL
Total bilirubin =< 1.5 mg/dL
AST (SGOT)/ALT (SGPT) =< 2.5 x institutional upper limit of normal
Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min
Computed tomography scan or MRI of the pelvis negative for metastatic disease within 3 months prior to registration
Bone scan negative for metastatic disease within 3 months prior to registration
Chest PA and lateral films negative for metastatic disease within 3 months prior to registration
Prior vaccine therapy is allowed if completed at least 6 months prior to registration
Men enrolled in this trial must agree to use adequate contraception prior to study entry and for the duration of study participation
Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

Patients who have had any prior cytotoxic chemotherapy
Patients may not be receiving any other investigational agents
Patients receiving concurrent chemotherapeutic agents, biological response modifiers, radiation therapy, corticosteroid or hormonal therapy; no complementary or alternative therapy (e.g., St. John's Wort, PC-SPES, or any 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 perifosine
Androgen deprivation given for reasons other than neoadjuvant or adjuvant therapy
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
HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with perifosine; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated
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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (perifosine)	laboratory biomarker analysis	Patients receive oral perifosine once daily on days 1-28. On day 1 of course 1 only, patients receive 2 doses of oral perifosine. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease by PSA alone may receive up to 3 additional courses of therapy after documentation of progression.
Treatment (perifosine)	perifosine	Patients receive oral perifosine once daily on days 1-28. On day 1 of course 1 only, patients receive 2 doses of oral perifosine. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease by PSA alone may receive up to 3 additional courses of therapy after documentation of progression.

Primary Outcome Measures

Name	Time	Method
PSA Response	Up to 6 years	A PSA normalization (PSA-N) - was recorded on case report forms for any evaluation in which the PSA level was undetectable (\< 0.1 ng/mL). If the PSA-N response was confirmed by a second measurement ≥ 4 weeks later, the patient's best PSA response was considered PSA-N. PSA-PR was recorded if the PSA decreased by ≥ 50% from baseline (pretreatment) values and confirmed by a second measurement ≥ 4 weeks later. PSA-PD was recorded upon the appearance of ≥ 1 new lesion on radiographs consistent with metastatic disease, an absolute increase in PSA value of 5 ng/mL relative to the lowest postenrollment PSA value (including the baseline PSA value), or if the PSA doubling time was \< 2 months. PSA-SD constituted responses that did not qualify for PSA-N, PSA-PR, or PSA-PD. Response = PSA-N + PSA-PR.

Secondary Outcome Measures

Name	Time	Method
Time to Progression	From the date of registration to the date of documented PSA progression, assessed up to 6 years	Estimated using the product-limit method of Kaplan and Meier. Progression was defined as the appearance of ≥ 1 new lesion on radiographs consistent with metastatic disease, an absolute increase in PSA value of 5 ng/mL relative to the lowest postenrollment PSA value (including the baseline PSA value), or if the PSA doubling time was \< 2 months.