Perifosine in Treating Patients With Recurrent Prostate Cancer

Adenocarcinoma of the Prostate Clinical Trial

Official title:

A Phase II Trial of Perifosine (IND 58,156; NSC# 639966) in Biochemically Recurrent, Hormone Sensitive Prostate Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00058214
• Other study ID #: NCI-2012-02832
• Secondary ID: PHII-44N01CM1710
• Status: Terminated
• Phase: Phase 2
• First received: April 7, 2003
• Last updated: February 9, 2015
• Start date: March 2003
• Est. completion date: January 2009

Study information

• Verified date: February 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Terminated
• Enrollment: 25
• Est. completion date: January 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Prostate
• Prostatic Neoplasms
• Recurrent Prostate Cancer
• Stage IIB Prostate Cancer
• Stage III Prostate Cancer
• Stage IV Prostate Cancer

Intervention

Drug:
• perifosine
Given orally

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	UC Davis Cancer Center	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PSA Response	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.	Up to 6 years	No
Secondary	Time to Progression	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.	From the date of registration to the date of documented PSA progression, assessed up to 6 years	No