Adenocarcinoma of the Prostate, Recurrent Prostate Cancer, Stage IIB Prostate Cancer, Stage III Prostate Cancer, Stage IV Prostate Cancer
Conditions
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.
Interventions
DRUGperifosine
Given orally
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Perifosine) Patients receive oral perifosine 100 mg once daily on days 1-28. On day 1 of course 1 only, patients receive 2 doses of oral perifosine at 450 mg. 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.
perifosine: Given orally
laboratory biomarker analysis: Correlative studies | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Treatment (Perifosine) |
|---|---|
| Age, Continuous | 67 years |
| Region of Enrollment United States | 25 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 25 / 25 |
| serious Total, serious adverse events | 1 / 25 |
Outcome results
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.
Time frame: Up to 6 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Perifosine) | PSA Response | 0 percentage of participants |
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.
Time frame: From the date of registration to the date of documented PSA progression, assessed up to 6 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Perifosine) | Time to Progression | 6.64 months |