Prostate Cancer
Conditions
Brief summary
This is an open label, single center Phase II trial of Sandostatin LAR in patients with hormone refractory prostate cancer. Patients will receive Sandostatin LAR 30 mg intramuscularly every 28 days. Patients will be treated until the time of disease progression, unacceptable toxicity or withdrawal of consent. The study will require 27 evaluable patients.
Detailed description
Primary Objective: To evaluate changes in prostate specific antigen (PSA) in patients with androgen independent prostate cancer who are treated with Sandostatin LAR. Secondary Objective: To evaluate the effects of Sandostatin LAR on circulating levels of Insulin Growth Factor-1 and Insulin Growth Factor Binding Protein 1. To evaluate the safety of Sandostatin LAR in this patient population. To evaluate the pre versus post treatment mitogenic effects of serum derived from subjects with prostate cancer compared to pretreatment serum. Patients with androgen independent prostate cancer who do not have bone or visceral metastases are selected for this trial because they are a patient population that is likely to have no symptoms from the disease or rapid progression that would suggest the need for chemotherapy. Additionally, given the preclinical data suggesting that IGF-1 expression and signaling occurs concomitantly with the onset of androgen independent growth, it is felt that testing in the early androgen independent state is warranted. This trial is consistent with overall goal to develop IGF-1 targeted therapies in patients with disease progression and a lower disease burden.
Interventions
DRUGSandostatin
Sandostatin 30mg intramuscular every 28 days
Sponsors
Novartis
University of California, San Francisco
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed adenocarcinoma of the prostate. * Biochemical disease progression following androgen deprivation and therapy with at least one antiandrogen defined as three rises in PSA with PSA determinations at least 4 weeks apart and each PSA value \> 0.2 ng/ml. * Four weeks since prior therapy with Flutamide. * Six weeks since prior therapy with Bicalutamide or Nilutamide. * Current PSA \> 5 ng/ml. * Testosterone \<50 ng/dL. * SGPT (ALT) \< 1.5 times upper limit of normal. * Fasting blood glucose \> 60 mg/dL. * ECOG performance status 0, 1 or 2. * No visceral or bony metastatic disease (Lymph node only metastases are allowed). * No prior chemotherapy for prostate cancer. * No current treatment with insulin or an oral hypoglycemic. * No history of treatment with octreotide analogs for prostate cancer. * No NYHA Class 3 or 4 cardiac status.
Exclusion criteria
* Diabetes Mellitus requiring medical therapy and/or that which is not controlled by dietary means (HbA1C\<6.0). * A history of gallstones that has been clinically significant. Patients who have undergone cholecystectomy are eligible. * Other concomitant medical or psychiatric condition which would make it undesirable, in the physician's opinion, for the patient to participate in the protocol or would jeopardize compliance with the protocol requirements. * Prior treatment with chemotherapy for prostate cancer. * No current treatment with Saw Palmetto, or Proscar. Patients must be off these medicines for more than 4 weeks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PSA Response | 12 weeks | Number of participants with a PSA decline of at least 50% from Baseline during the first 3 cycles of therapy, confirmed by a second measurement at least 2 weeks later. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pre-post Percent Change in Circulating Levels of IGF-1 and IGF-Binding Protein 1. | Baseline, 12 weeks | Serum was batched and IGF and IGFBP levels were assayed at one time at the end of the study using an enzyme-linked immunoabsorbent assay (ELISA) method by Diagnostic Systems Laboratories (Webster, TX). |
| Grade 4-5 Adverse Events | 12 weeks | — |
| Pre Versus Post Treatment Mitogenic Effects. | 12 Weeks | — |
Countries
United States
Participant flow
Recruitment details
Men with prostate adenocarcinoma that had progressed despite androgen deprivation therapy were recruited for participation at one U.S. clinical site (UCSF)
Participants by arm
| Arm | Count |
|---|---|
| Octreotide Acetate Octreotide acetate 30mg intramuscular every 28 days | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Octreotide Acetate |
|---|---|
| Age Continuous | 75 years |
| Gleason Score | 8 Score |
| Hemoglobin | 13.9 gm/dl |
| Median PSA | 36.2 ng/ml |
| Primary therapy Androgen Deprivation | 4 participants |
| Primary therapy Prostatectomy | 3 participants |
| Primary therapy Radiation Therapy | 6 participants |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
Primary
PSA Response
Number of participants with a PSA decline of at least 50% from Baseline during the first 3 cycles of therapy, confirmed by a second measurement at least 2 weeks later.
Time frame: 12 weeks
Population: n=27 was determined to be sufficient to test for a 20% PSA response proportion compared with a null hypothesis of 5%. A two-stage design was employed to carry out an interim analysis for efficacy. As no patient showed a PSA decline among the first 13 accrued after 3 cycles (the first evaluation of PSA response), accrual was discontinued
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Octreotide Acetate | PSA Response | 0 Participants |
Secondary
Grade 4-5 Adverse Events
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Octreotide Acetate | Grade 4-5 Adverse Events | 0 Adverse Events |
Secondary
Pre-post Percent Change in Circulating Levels of IGF-1 and IGF-Binding Protein 1.
Serum was batched and IGF and IGFBP levels were assayed at one time at the end of the study using an enzyme-linked immunoabsorbent assay (ELISA) method by Diagnostic Systems Laboratories (Webster, TX).
Time frame: Baseline, 12 weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Octreotide Acetate | Pre-post Percent Change in Circulating Levels of IGF-1 and IGF-Binding Protein 1. | IGFBP-1 | 76.3 percent change |
| Octreotide Acetate | Pre-post Percent Change in Circulating Levels of IGF-1 and IGF-Binding Protein 1. | IGF-1 | -34.5 percent change |
Secondary
Pre Versus Post Treatment Mitogenic Effects.
Time frame: 12 Weeks
Population: The trial was closed for futility after no PSA responses were observed among the first 13 patients, and this analysis was not performed