Trial Outcomes & Findings for Androgen Deprivation Therapy and Vorinostat Followed by Radical Prostatectomy in Treating Patients With Localized Prostate Cancer (NCT NCT00589472)

Results Overview

The primary endpoint will be pathologic complete response at the time of surgery. This represents the proportion of patients with no evidence of disease in the prostate (ie, the absence of tumor in the posttherapy pathology specimen) at the time of radical prostatectomy. Pathologic complete response at the time of surgery is the primary endpoint for this study. A Simon 2-stage optimal design that differentiates between response probabilities of 0.05 and 0.20 will be used in the analysis of the pathological complete response at 12 weeks (Type I error 10% and power 90%). A maximum of 38 pts were planned for accrual onto this study. If zero or one response was observed, then the trial was to be stopped. The design had power 0.90 for a population response proportion to 0.20 using a one-sided 0.10 size test. pT2 indicates that the cancer is confined to the prostate, while pT3 indicates that there is an extraprostatic extension of the cancer.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

19 participants

Primary outcome timeframe

At 12 weeks

Results posted on

2017-10-06

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Antihormone Therapy and Enzyme Inhibitor Therapy) Patients receive bicalutamide PO QD for 1 month and leuprolide acetate IM or goserelin acetate SC once a month until surgery. Patients also receive vorinostat PO QD beginning on the first day of androgen depletion therapy and continuing for up to 8 weeks or until the day of surgery. Patients then undergo an open or laparoscopic radical prostatectomy. Patients with positive surgical margins undergo immediate adjuvant external beam radiotherapy to the prostatic fossa, based on the judgment of the treating physician. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Therapeutic Conventional Surgery: Undergo radical prostatectomy Vorinostat: Given PO
Overall Study STARTED	19
Overall Study COMPLETED	18
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Antihormone Therapy and Enzyme Inhibitor Therapy) Patients receive bicalutamide PO QD for 1 month and leuprolide acetate IM or goserelin acetate SC once a month until surgery. Patients also receive vorinostat PO QD beginning on the first day of androgen depletion therapy and continuing for up to 8 weeks or until the day of surgery. Patients then undergo an open or laparoscopic radical prostatectomy. Patients with positive surgical margins undergo immediate adjuvant external beam radiotherapy to the prostatic fossa, based on the judgment of the treating physician. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Therapeutic Conventional Surgery: Undergo radical prostatectomy Vorinostat: Given PO
Overall Study Adverse Event	1

Baseline Characteristics

Androgen Deprivation Therapy and Vorinostat Followed by Radical Prostatectomy in Treating Patients With Localized Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Antihormone Therapy and Enzyme Inhibitor Therapy) n=19 Participants Patients receive bicalutamide PO QD for 1 month and leuprolide acetate IM or goserelin acetate SC once a month until surgery. Patients also receive vorinostat PO QD beginning on the first day of androgen depletion therapy and continuing for up to 8 weeks or until the day of surgery. Patients then undergo an open or laparoscopic radical prostatectomy. Patients with positive surgical margins undergo immediate adjuvant external beam radiotherapy to the prostatic fossa, based on the judgment of the treating physician. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Therapeutic Conventional Surgery: Undergo radical prostatectomy Vorinostat: Given PO
Age, Categorical <=18 years	0 Participants n=113 Participants
Age, Categorical Between 18 and 65 years	14 Participants n=113 Participants
Age, Categorical >=65 years	5 Participants n=113 Participants
Sex: Female, Male Female	0 Participants n=113 Participants
Sex: Female, Male Male	19 Participants n=113 Participants

PRIMARY outcome

Timeframe: At 12 weeks

The primary endpoint will be pathologic complete response at the time of surgery. This represents the proportion of patients with no evidence of disease in the prostate (ie, the absence of tumor in the posttherapy pathology specimen) at the time of radical prostatectomy. Pathologic complete response at the time of surgery is the primary endpoint for this study. A Simon 2-stage optimal design that differentiates between response probabilities of 0.05 and 0.20 will be used in the analysis of the pathological complete response at 12 weeks (Type I error 10% and power 90%). A maximum of 38 pts were planned for accrual onto this study. If zero or one response was observed, then the trial was to be stopped. The design had power 0.90 for a population response proportion to 0.20 using a one-sided 0.10 size test. pT2 indicates that the cancer is confined to the prostate, while pT3 indicates that there is an extraprostatic extension of the cancer.

Outcome measures

Outcome measures
Measure	Treatment (Antihormone Therapy and Enzyme Inhibitor Therapy) n=18 Participants Patients receive bicalutamide PO QD for 1 month and leuprolide acetate IM or goserelin acetate SC once a month until surgery. Patients also receive vorinostat PO QD beginning on the first day of androgen depletion therapy and continuing for up to 8 weeks or until the day of surgery. Patients then undergo an open or laparoscopic radical prostatectomy. Patients with positive surgical margins undergo immediate adjuvant external beam radiotherapy to the prostatic fossa, based on the judgment of the treating physician. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Therapeutic Conventional Surgery: Undergo radical prostatectomy Vorinostat: Given PO
Pathologic Complete Response at the Time of Surgery pT2	10 Participants
Pathologic Complete Response at the Time of Surgery pT3	8 Participants
Pathologic Complete Response at the Time of Surgery Complete Response	0 Participants

SECONDARY outcome

Timeframe: Baseline

A Gleason score is the sum of two numbers. Pathologist determines where the cancer is most prominent and assigns the primary grade, the secondary grade is assigned based on where the cancer is next most prominent. A score from one to five is assigned for each area based on how aggressive the tumor appears. A tumor with cell that appear close to normal is assigned a low Gleason score (six or below). A tumor with cells that appear clearly different from those of a normal prostate is assigned a high Gleason score (seven or above). A system of grading prostate cancer tissue based on how it looks under a microscope. Gleason scores range from 2 to 10 and indicate how likely it is that a tumor will spread. A low Gleason score means the cancer tissue is similar to normal prostate tissue and the tumor is less likely to spread; a high Gleason score means the cancer tissue is very different from normal and the tumor is more likely to spread.

Outcome measures

Outcome measures
Measure	Treatment (Antihormone Therapy and Enzyme Inhibitor Therapy) n=18 Participants Patients receive bicalutamide PO QD for 1 month and leuprolide acetate IM or goserelin acetate SC once a month until surgery. Patients also receive vorinostat PO QD beginning on the first day of androgen depletion therapy and continuing for up to 8 weeks or until the day of surgery. Patients then undergo an open or laparoscopic radical prostatectomy. Patients with positive surgical margins undergo immediate adjuvant external beam radiotherapy to the prostatic fossa, based on the judgment of the treating physician. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Therapeutic Conventional Surgery: Undergo radical prostatectomy Vorinostat: Given PO
Gleason Score	8 units on a scale Interval 6.0 to 9.0

SECONDARY outcome

Timeframe: Up to 1 year

Outcome measures

Outcome measures
Measure	Treatment (Antihormone Therapy and Enzyme Inhibitor Therapy) n=18 Participants Patients receive bicalutamide PO QD for 1 month and leuprolide acetate IM or goserelin acetate SC once a month until surgery. Patients also receive vorinostat PO QD beginning on the first day of androgen depletion therapy and continuing for up to 8 weeks or until the day of surgery. Patients then undergo an open or laparoscopic radical prostatectomy. Patients with positive surgical margins undergo immediate adjuvant external beam radiotherapy to the prostatic fossa, based on the judgment of the treating physician. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Therapeutic Conventional Surgery: Undergo radical prostatectomy Vorinostat: Given PO
Levels of DHEA in Blood From Radical Prostatectomy Specimens	256 ng/dL Interval 81.0 to 461.0

SECONDARY outcome

Timeframe: Up to 1 year

Outcome measures

Outcome measures
Measure	Treatment (Antihormone Therapy and Enzyme Inhibitor Therapy) n=18 Participants Patients receive bicalutamide PO QD for 1 month and leuprolide acetate IM or goserelin acetate SC once a month until surgery. Patients also receive vorinostat PO QD beginning on the first day of androgen depletion therapy and continuing for up to 8 weeks or until the day of surgery. Patients then undergo an open or laparoscopic radical prostatectomy. Patients with positive surgical margins undergo immediate adjuvant external beam radiotherapy to the prostatic fossa, based on the judgment of the treating physician. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Therapeutic Conventional Surgery: Undergo radical prostatectomy Vorinostat: Given PO
Levels of DHEA-S in Blood From Radical Prostatectomy Specimens	90 mcg/dL Interval 24.9 to 221.0

SECONDARY outcome

Timeframe: Up to 1 year

Outcome measures

Outcome measures
Measure	Treatment (Antihormone Therapy and Enzyme Inhibitor Therapy) n=18 Participants Patients receive bicalutamide PO QD for 1 month and leuprolide acetate IM or goserelin acetate SC once a month until surgery. Patients also receive vorinostat PO QD beginning on the first day of androgen depletion therapy and continuing for up to 8 weeks or until the day of surgery. Patients then undergo an open or laparoscopic radical prostatectomy. Patients with positive surgical margins undergo immediate adjuvant external beam radiotherapy to the prostatic fossa, based on the judgment of the treating physician. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Therapeutic Conventional Surgery: Undergo radical prostatectomy Vorinostat: Given PO
Levels of DHT in Blood From Radical Prostatectomy Specimens	24 ng/dL Interval 2.0 to 54.0

SECONDARY outcome

Timeframe: Up to 1 year

Outcome measures

Outcome measures
Measure	Treatment (Antihormone Therapy and Enzyme Inhibitor Therapy) n=18 Participants Patients receive bicalutamide PO QD for 1 month and leuprolide acetate IM or goserelin acetate SC once a month until surgery. Patients also receive vorinostat PO QD beginning on the first day of androgen depletion therapy and continuing for up to 8 weeks or until the day of surgery. Patients then undergo an open or laparoscopic radical prostatectomy. Patients with positive surgical margins undergo immediate adjuvant external beam radiotherapy to the prostatic fossa, based on the judgment of the treating physician. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Therapeutic Conventional Surgery: Undergo radical prostatectomy Vorinostat: Given PO
Levels of PSA in Blood From Radical Prostatectomy Specimens	9.44 ng/mL Interval 1.19 to 41.3

SECONDARY outcome

Timeframe: Up to 1 year

Outcome measures

Outcome measures
Measure	Treatment (Antihormone Therapy and Enzyme Inhibitor Therapy) n=18 Participants Patients receive bicalutamide PO QD for 1 month and leuprolide acetate IM or goserelin acetate SC once a month until surgery. Patients also receive vorinostat PO QD beginning on the first day of androgen depletion therapy and continuing for up to 8 weeks or until the day of surgery. Patients then undergo an open or laparoscopic radical prostatectomy. Patients with positive surgical margins undergo immediate adjuvant external beam radiotherapy to the prostatic fossa, based on the judgment of the treating physician. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Therapeutic Conventional Surgery: Undergo radical prostatectomy Vorinostat: Given PO
Levels of Testosterone in Blood From Radical Prostatectomy Specimens	319 ng/dL Interval 138.0 to 521.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 1 year

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 1 year

Adverse events will be monitored at each scheduled visit and throughout the study. Toxicity will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Treatment (Antihormone Therapy and Enzyme Inhibitor Therapy)

Serious events: 2 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Antihormone Therapy and Enzyme Inhibitor Therapy) n=19 participants at risk Patients receive bicalutamide PO QD for 1 month and leuprolide acetate IM or goserelin acetate SC once a month until surgery. Patients also receive vorinostat PO QD beginning on the first day of androgen depletion therapy and continuing for up to 8 weeks or until the day of surgery. Patients then undergo an open or laparoscopic radical prostatectomy. Patients with positive surgical margins undergo immediate adjuvant external beam radiotherapy to the prostatic fossa, based on the judgment of the treating physician. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Therapeutic Conventional Surgery: Undergo radical prostatectomy Vorinostat: Given PO
Cardiac disorders Thrombosis	5.3% 1/19 • Number of events 1 • Up to 30 days after treatment
Vascular disorders Hypertension	5.3% 1/19 • Number of events 1 • Up to 30 days after treatment

Other adverse events

Other adverse events
Measure	Treatment (Antihormone Therapy and Enzyme Inhibitor Therapy) n=19 participants at risk Patients receive bicalutamide PO QD for 1 month and leuprolide acetate IM or goserelin acetate SC once a month until surgery. Patients also receive vorinostat PO QD beginning on the first day of androgen depletion therapy and continuing for up to 8 weeks or until the day of surgery. Patients then undergo an open or laparoscopic radical prostatectomy. Patients with positive surgical margins undergo immediate adjuvant external beam radiotherapy to the prostatic fossa, based on the judgment of the treating physician. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Therapeutic Conventional Surgery: Undergo radical prostatectomy Vorinostat: Given PO
Investigations Activated partial thromboplastin time prolonged	5.3% 1/19 • Number of events 1 • Up to 30 days after treatment
Blood and lymphatic system disorders Anemia	57.9% 11/19 • Number of events 24 • Up to 30 days after treatment
Investigations Blood bilirubin increased	5.3% 1/19 • Number of events 1 • Up to 30 days after treatment
Cardiac disorders Cardiac disorders-Other, specify	5.3% 1/19 • Number of events 1 • Up to 30 days after treatment
Psychiatric disorders Confusion	5.3% 1/19 • Number of events 1 • Up to 30 days after treatment
Investigations Creatinine increased	10.5% 2/19 • Number of events 3 • Up to 30 days after treatment
Reproductive system and breast disorders Erectile dysfunction	5.3% 1/19 • Number of events 1 • Up to 30 days after treatment
General disorders Fatigue	5.3% 1/19 • Number of events 1 • Up to 30 days after treatment
Nervous system disorders Headache	5.3% 1/19 • Number of events 1 • Up to 30 days after treatment
Metabolism and nutrition disorders Hyperglycemia	57.9% 11/19 • Number of events 28 • Up to 30 days after treatment
Vascular disorders Hypertension	10.5% 2/19 • Number of events 2 • Up to 30 days after treatment
Metabolism and nutrition disorders Hypocalcemia	42.1% 8/19 • Number of events 20 • Up to 30 days after treatment
Metabolism and nutrition disorders Hypokalemia	5.3% 1/19 • Number of events 1 • Up to 30 days after treatment
Metabolism and nutrition disorders Hypophosphatemia	5.3% 1/19 • Number of events 2 • Up to 30 days after treatment
Investigations INR increased	10.5% 2/19 • Number of events 3 • Up to 30 days after treatment
Investigations Lymphocyte count decreased	21.1% 4/19 • Number of events 6 • Up to 30 days after treatment
Investigations Neutrophil count decreased	5.3% 1/19 • Number of events 1 • Up to 30 days after treatment
General disorders Pain	5.3% 1/19 • Number of events 1 • Up to 30 days after treatment

Additional Information

Dr. Susan Slovin

Memorial Sloan Kettering Cancer Center

Phone: 646-422-4470

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60