Prostate Cancer
Conditions
Keywords
Neoadjuvant Prostate Cancer, Abiraterone Acetate, LHRHa, high risk prostate cancer, Radical prostatectomy, Prednisone, Luteinizing Hormone-Releasing Hormone, LHRH analogue
Brief summary
The goal of this clinical research study is to find out how treatment with abiraterone acetate in combination with prednisone and a Luteinizing Hormone-Releasing Hormone (LHRH) analogue changes the tumor in comparison to treatment with an LHRH analogue alone. Objectives: Primary Objective: To assess the difference in pathologic stage \< pT2 between Group A and Group B. Secondary Objective: * To assess and compare the changes in levels of androgens (pre, during, and post treatment) in the serum, primary tumor microenvironment and bone marrow between Group A and Group B. * To assess changes in biomarkers related to androgen signaling and other cancer-related pathways between Group A and Group B. * To assess the difference in rate of positive surgical margins between Group A and Group B. * To assess the safety profile of abiraterone acetate and low dose prednisone in a preoperative setting.
Detailed description
Study Groups: Participants who are eligible to take part in this study will be randomly assigned (as in the flip of a coin) to 1 of 2 groups: * Those who are in Group A will take abiraterone acetate, a LHRH analogue, and prednisone. * Those who are in Group B will receive a LHRH analogue alone. Participants will have 2 out of 3 chances of being placed in Group A or 1 out of 3 chances of being placed in Group B. Participants in both groups will receive the study drug(s) for about 3 months followed by a prostatectomy (prostate surgery) between 2 and 4 weeks after they stop taking the study drug(s). Length of Study: Participants will receive study drugs on this study for about 3 months before having surgery to remove their prostate about 2-4 weeks later. Participants will be removed from this study if the disease gets worse, if they experience intolerable side effects, or their study doctors feel that it is in their best interest to stop the study. Long-Term Follow-Up: Participants will return to the clinic 1 month, 3 months, 6 months, and then every 6 months (for up to 8 years) after your surgery for follow-up visits. Up to 66 patients will be take part in this study. All will be enrolled at M. D. Anderson after their surgery.
Interventions
DRUGAbiraterone Acetate
1000 mg oral daily for 3 months followed by a prostatectomy.
DRUGPrednisone
5 mg orally daily.
DRUGLHRHa
LHRH analogue (either leuprolide or goserelin): Leuprolide is an intramuscular injection, and goserelin subcutaneous (under skin) of abdomen, given either 1 injection every 3 months or 1 injection each month for 3 months.
Sponsors
Cougar Biotechnology, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histological proof of prostatic adenocarcinoma via a minimum of 6 core biopsy samples 2. Clinical stage T1c or T2 with high-grade disease (Gleason's 8-10) on initial biopsy, or clinical stage T2b-T2c with Gleason's grade \>/= 7 and PSA \> 10ng/ml. 3. No evidence of metastatic disease as determined by CT scans and bone scans. 4. Eastern Cooperative Oncology Group (ECOG) Performance Status of \</= 1 5. Patients should have adequate bone marrow function defined as an absolute peripheral granulocyte count (ANC) \> 1,500 and platelet count of \> 100,000. 6. Normal pituitary and adrenal function 7. Patients should be deemed to be candidates for radical prostatectomy.
Exclusion criteria
1. Histological variants in the primary tumor (histological variants other than adenocarcinoma); neuroendocrine tumor 2. Serious or uncontrolled co-existent non-malignant disease, including active and uncontrolled infection 3. Uncontrolled hypertension 4. Abnormal Liver function 5. Active or symptomatic viral hepatitis or chronic liver disease 6. Clinically significant heart disease 7. Other active malignancy 8. History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug 9. Previous treatment with abiraterone acetate 10. Patients who are not appropriate surgical candidates for radical prostatectomy 11. Prior chemotherapy or radiation therapy for prostate cancer. 12. Condition or situation which, in the investigator's opinion, may put the patient at significant risk, may confound the study results, or may interfere significantly with patient's participation in the study Note: There are additional inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Pathology Tumor Stage of Less Than or Equal to Prostate Cancer Stage at Which the Tumor is Confined to the Prostate (pT2) | At the end of Cycle 3 (at radical prostatectomy) | The table below shows number of participants in each treatment group with a pathology tumor stage less than or equal to pT2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Positive Surgical Margin at Radical Prostatectomy | At the end of Cycle 3 (at radical prostatectomy) | The table below shows number of participants in each treatment group who had positive surgical margins. A positive surgical margin is defined as tumor extending to the inked-surface or margin of the prostate. |
| Number of Participants With Prostate-Specific Antigen Response | Cycle 3 Day 1 | The table below shows number of participants in each treatment group who achieved a prostate-specific antigen (PSA) response defined as a drop in PSA value to less than or equal to 0.2 ng/mL. |
Countries
United States
Participant flow
Recruitment details
The study was conducted from 20 November 2009 to 14 March 2013. Participants were recruited at 1 study center in the United States.
Pre-assignment details
66 participants were randomly allocated to the 2 treatment arms and were included in the intent-to-treat (ITT) analysis set. 65 participants received at least 1 dose of the study drug and were included in the safety analysis set.
Participants by arm
| Arm | Count |
|---|---|
| AA+LHRHa Participants received luteinizing hormone-releasing hormone analog (LHRHa) for a maximum of 4 months (monthly injection or injection every 3 months) and 1,000 mg abiraterone acetate (AA) plus 5 mg of prednisone daily for 3 months prior to radical prostatectomy | 44 |
| LHRHa Participants received luteinizing hormone-releasing hormone analog (LHRHa) for a maximum of 4 months (monthly injection or injection every 3 months) prior to radical prostatectomy. | 22 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not receive study treatment | 0 | 1 |
Baseline characteristics
| Characteristic | AA+LHRHa | LHRHa | Total |
|---|---|---|---|
| Age, Continuous | 61.6 years STANDARD_DEVIATION 7.14 | 59.9 years STANDARD_DEVIATION 7.6 | 61 years STANDARD_DEVIATION 7.29 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 44 Participants | 22 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 43 / 44 | 21 / 21 |
| serious Total, serious adverse events | 2 / 44 | 2 / 21 |
Outcome results
Primary
Number of Participants With a Pathology Tumor Stage of Less Than or Equal to Prostate Cancer Stage at Which the Tumor is Confined to the Prostate (pT2)
The table below shows number of participants in each treatment group with a pathology tumor stage less than or equal to pT2.
Time frame: At the end of Cycle 3 (at radical prostatectomy)
Population: Intent-to-treat (ITT) analysis set, which included all participants who were randomized to study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AA+LHRHa | Number of Participants With a Pathology Tumor Stage of Less Than or Equal to Prostate Cancer Stage at Which the Tumor is Confined to the Prostate (pT2) | 24 participants |
| LHRHa | Number of Participants With a Pathology Tumor Stage of Less Than or Equal to Prostate Cancer Stage at Which the Tumor is Confined to the Prostate (pT2) | 8 participants |
p-value: 0.214890% CI: [0.859, 2.386]Chi-squared
Secondary
Number of Participants With a Positive Surgical Margin at Radical Prostatectomy
The table below shows number of participants in each treatment group who had positive surgical margins. A positive surgical margin is defined as tumor extending to the inked-surface or margin of the prostate.
Time frame: At the end of Cycle 3 (at radical prostatectomy)
Population: Intent-to-treat (ITT) analysis set, which included all participants who were randomized to study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AA+LHRHa | Number of Participants With a Positive Surgical Margin at Radical Prostatectomy | 6 participants |
| LHRHa | Number of Participants With a Positive Surgical Margin at Radical Prostatectomy | 6 participants |
p-value: 0.179690% CI: [0.205, 1.109]Fisher Exact
Secondary
Number of Participants With Prostate-Specific Antigen Response
The table below shows number of participants in each treatment group who achieved a prostate-specific antigen (PSA) response defined as a drop in PSA value to less than or equal to 0.2 ng/mL.
Time frame: Cycle 3 Day 1
Population: Intent-to-treat (ITT) analysis set, which included all participants who were randomized to study. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AA+LHRHa | Number of Participants With Prostate-Specific Antigen Response | 32 participants |
| LHRHa | Number of Participants With Prostate-Specific Antigen Response | 0 participants |
p-value: <0.000190% CI: [2.701, 15.753]Chi-squared