A Phase 1 Study To Evaluate Escalating Doses Of A Vaccine-Based Immunotherapy Regimen For Prostate Cancer (PrCa VBIR)

Prostatic Neoplasms Clinical Trial

Official title:

A PHASE 1 STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS AND PHARMACODYNAMICS OF ESCALATING DOSES OF A VACCINE-BASED IMMUNOTHERAPY REGIMEN (VBIR) FOR PROSTATE CANCER (PF-06753512)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02616185
• Other study ID #: B7791001
• Secondary ID: PRCA VBIR FIP ST
• Status: Terminated
• Phase: Phase 1
• Start date: December 30, 2015
• Est. completion date: February 23, 2021

Study information

• Verified date: January 2023
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study will evaluate the safety, pharmacokinetics and pharmacodynamics of increasing doses of a vaccine-based immunotherapy regimen for patients with prostate cancer.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 91
• Est. completion date: February 23, 2021
• Est. primary completion date: February 23, 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histological or cytological diagnosis of prostate cancer

• Adequate bone marrow, kidney and liver function

• Hormone sensitive relapsing prostate cancer after definitive local therapy (biochemical relapse) OR

• Failed prior therapy with a novel hormone (e.g. enzalutamide, abiraterone) with documented progressive disease (post-novel hormone therapy CRPC)

Exclusion Criteria:

• ECOG performance status greater than or equal to 2

• Concurrent immunotherapy for prostate cancer

• History of or active autoimmune disorders (including but not limited to: myasthenia gravis, thyroiditis, pneumonitis, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, scleroderma) and other conditions that disorganize or alter the immune system.

• History of inflammatory bowel disease.

• Current use of any implanted electronic stimulation device

• For biochemically relapsed patients, no concurrent use of ADT or orchiectomy and no known prior or current evidence of any metastatic involvement of distant organs

• For post-novel hormone patients, no concurrent treatment with a secondary hormone (e.g. enzalutamide, abiraterone), no metastasis to the liver or brain

Related Conditions & MeSH terms

• Prostatic Neoplasms

Intervention

Biological:
• PF-06755992
PF-06755992 will be administered on Day 1 of Cycles 1 and 2.
• PF-06755990
PF-06755990 will be administered using a device on Day 29, 57 and 85 of each cycle.

Device:
• TDS-IM Electroporation Device
TDS-IM electroporation device and associated supplies will be used for PF-06755990 administration

Biological:
• Tremelimumab
PF-06753388 will be administered every 28 days.
• PF-06801591
PF-06801591 will be administered every 28 days.
• PF-06753512
Combination of adenovirus (AdC68) + plasmid DNA (pDNA) + tremelimumab

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland
United States	Duke University Medical Center	Durham	North Carolina
United States	Northwell Health	Lake Success	New York
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Garden State Urology	Morristown	New Jersey
United States	Morristown Medical Center	Morristown	New Jersey
United States	Smilow Cancer Hospital at Yale-New Haven	New Haven	Connecticut
United States	Smilow Cancer Hospital Phase 1 Unit	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan-Kettering Cancer Center 53rd Street	New York	New York
United States	Memorial Sloan-Kettering Cancer Center, Sidney Kimmel Center	New York	New York
United States	GU Research Network	Omaha	Nebraska
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Garden State Urology	Rockaway	New Jersey
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Banner-University Medical Center Tucson	Tucson	Arizona
United States	The University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	Garden State Urology	Whippany	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a clinical investigation where participant administered a product; the event did not need to have a causal relationship with the treatment. A SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and non-serious AEs.	Baseline up to 6 months after End of Treatment (EOT; 52 months in maximum)
Primary	Number of Participants With AEs as Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) (Grade >= 3)	An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. Grades of AEs were defined by NCI CTCAE v 4.03. Grade 1=asymptomatic/mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activity of daily living (ADL); Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5= death related to AE. Treatment-emergent adverse events occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.	Baseline up to 6 months after EOT (52 months in maximum)
Primary	Number of Participants With AEs Leading to Discontinuation or Dose Reduction	An AE was any untoward medical occurrence in a clinical investigation where participant administered a product; the event did not need to have a causal relationship with the treatment.	Baseline up to 6 months after EOT (52 months in maximum)
Primary	Number of Participants With Dose-Limiting Toxicities (DLTs)	The following AEs occurring in the first 28 days following the first AdC68 vaccination and not related to disease/progression were DLTs: (a) hematologic (Cohorts 1A to 3A and Cohorts 6A to 9A): Grade 3 neutropenia lasting >7 days, febrile neutropenia, Grade >=3 neutropenic infection, Grade >=3 thrombocytopenia, Grade >=3 anemia lasting >7 days, Grade >=3 lymphopenia lasting >14 days; (b) non-hematologic (all cohorts): Grade >=3 laboratory abnormalities either associated with symptoms or associated with worsening of an existing condition or that suggested a new disease process or that required additional active management, Grade >=3 toxicities, Grade 3 flu like symptoms lasting >3 days, fever of >40.0 degree Celsius lasting >3 days. Other clinically important or persistent toxicities at discretion of investigator and Pfizer.	The first 28 days following the first AdC68 vaccination (on Cycle 1 Day 1)
Secondary	Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4)	Laboratory abnormalities were graded per NCI CTCAE version 4.03 (Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) and those with at least 1 participant are presented here. Hematology parameters included hemoglobin, platelets, white blood cell count, neutrophils, eosinophils, monocytes, basophils and lymphocytes.	Baseline up to 6 months after EOT (52 months in maximum)
Secondary	Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4)	Laboratory abnormalities were graded per NCI CTCAE version 4.03 (Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) and those with at least 1 participant are presented here. Chemistry parameters included aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen (or urea), creatinine, uric acid, glucose, albumin, phosphorous or phosphate, lactate dehydrogenase, lipase, bicarbonate or carbon dioxide, total protein, TSH (if abnormal, reflex free T4 and free T3).	Baseline up to 6 months after EOT (52 months in maximum)
Secondary	Number of Participants With Laboratory Abnormalities in Urinalysis (Grade 3 or 4)	Laboratory abnormalities were graded per NCI CTCAE version 4.03 (Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) and those with at least 1 participant are presented here. Urine parameters included urine protein and urine blood.	Baseline up to 6 months after EOT (52 months in maximum)
Secondary	Change From Baseline in T Cell Response to Prostate Specific Antigen (PSA) in Part A	T cell response to PSA was determined by assaying peripheral blood mononuclear cell (PBMC) samples for cellular immune responses against PSA antigens and was determined as the frequency of interferon-gamma (IFN-?) spot forming cells (SFC)/million PBMCs. Change from baseline at Cycle 1 Day 71 and at Cycle 2 Day 99 are presented here.	At screening; Cycle 1: at Day 1, Day 15, Day 29, Day 43, Day 71; Cycle 2: at Day 1, Day 29, and Day 99; at the EOT visit, and 2, 4 and 6 months after EOT.
Secondary	Change From Baseline in T Cell Response to Prostate Stem Cell Antigen (PSCA) in Part A	T cell response to PSCA was determined by assaying PBMC samples for cellular immune responses against PSCA antigens and was determined as the frequency of IFN-? SFC/million PBMCs. Change from baseline at Cycle 1 Day 71 and at Cycle 2 Day 99 are presented here.	At screening; Cycle 1: at Day 1, Day 15, Day 29, Day 43, Day 71; Cycle 2: at Day 1, Day 29, and Day 99; at the EOT visit, and 2, 4 and 6 months after EOT.
Secondary	Change From Baseline in T Cell Response to Prostate Specific Membrane Antigen (PSMA) in Part A	T cell response to PSMA was determined by assaying PBMC samples for cellular immune responses against PSMA antigens and was determined as the frequency of IFN-? SFC/million PBMCs. Change from baseline at Cycle 1 Day 71 and at Cycle 2 Day 99 are presented here.	At screening; Cycle 1: at Day 1, Day 15, Day 29, Day 43, Day 71; Cycle 2: at Day 1, Day 29, and Day 99; at the EOT visit, and 2, 4 and 6 months after EOT.
Secondary	Maximum Observed Plasma Concentration (Cmax) of Tremelimumab in Part A	Cmax was defined as the maximum observed plasma concentration. Blood samples (approximately 3 mL whole blood) to provide at least 1 mL of serum for measurement of tremelimumab PK analysis were collected.	Cycle 1: at Day 1 pre-dose, any time between 48 to 120 hr, approximately 168 hr, 336 hr, and 504 hr, at pre-dose on Day 29, Day 57, and Day 85; Cycle 2: at pre-dose on Day 1 and Day 29; at EOT visit, and 2, 4 and 6 months after EOT.
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tremelimumab in Part A	Tmax was defined as the time to reach maximum observed plasma concentration. Blood samples (approximately 3 mL whole blood) to provide at least 1 mL of serum for measurement of tremelimumab PK analysis were collected.	Cycle 1: at Day 1 pre-dose, any time between 48 to 120 hr, approximately 168 hr, 336 hr, and 504 hr, at pre-dose on Day 29, Day 57, and Day 85; Cycle 2: at pre-dose on Day 1 and Day 29; at EOT visit, and 2, 4 and 6 months after EOT.
Secondary	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Tremelimumab in Part A	AUClast was defined as the area under the curve from time zero to last quantifiable concentration. Blood samples (approximately 3 mL whole blood) to provide at least 1 mL of serum for measurement of tremelimumab PK analysis were collected.	Cycle 1: at Day 1 pre-dose, any time between 48 to 120 hr, approximately 168 hr, 336 hr, and 504 hr, at pre-dose on Day 29, Day 57, and Day 85; Cycle 2: at pre-dose on Day 1 and Day 29; at EOT visit, and 2, 4 and 6 months after EOT.
Secondary	Trough Concentrations (Ctrough) After Multiple Dosing of Tremelimumab	Pre-dose tremelimumab concentration on Cycle 2 Day 1 is presented here as Ctrough. Blood samples (approximately 3 mL whole blood) to provide at least 1 mL of serum for measurement of tremelimumab PK analysis were collected. Summary statistics of Ctrough were not calculated if number of observations above lower lit of quantification (NALQ)=0 or <=3 participants had non-missing data.	Pre-dose on Cycle 2 Day 1
Secondary	Cmax of PF-06801591 in Part A	Cmax was defined as the maximum observed plasma concentration. Blood samples (approximately 5 mL) to provide serum for the analysis of PF-06801591 concentrations were collected.	Cycle 1: at Day 1 pre-dose, any time between 48 to 120 hr, approximately 168 hr, 336 hr, and 504 hr, at pre-dose on Day 29, Day 57, and Day 85; Cycle 2: at pre-dose on Day 1 and Day 29; at EOT visit, and 2, 4 and 6 months after EOT.
Secondary	Tmax of PF-06801591 in Part A	Tmax was defined as the time at which Cmax occurred. Blood samples (approximately 5 mL) to provide serum for the analysis of PF- 06801591 concentrations were collected.	Cycle 1: at Day 1 pre-dose, any time between 48 to 120 hr, approximately 168 hr, 336 hr, and 504 hr, at pre-dose on Day 29, Day 57, and Day 85; Cycle 2: at pre-dose on Day 1 and Day 29; at EOT visit, and 2, 4 and 6 months after EOT.
Secondary	AUClast of PF-06801591 in Part A	AUClast was defined as the area under the curve from time zero to last quantifiable concentration. Blood samples (approximately 5 mL) to provide serum for the analysis of PF-06801591 concentrations were collected. The geometric mean and geometric coefficient of variation of AUClast for Cohort 9A were not presented because fewer than 3 participants had reportable parameter values.	Cycle 1: at Day 1 pre-dose, any time between 48 to 120 hr, approximately 168 hr, 336 hr, and 504 hr, at pre-dose on Day 29, Day 57, and Day 85; Cycle 2: at pre-dose on Day 1 and Day 29; at EOT visit, and 2, 4 and 6 months after EOT.
Secondary	Ctrough of PF-06801591	Pre-dose PF-06801591 concentration on Cycle 2 Day 1 is presented here as Ctrough. Blood samples (approximately 3 mL whole blood) to provide at least 1 mL of serum for measurement of PF-06801591 PK analysis were collected.	Pre-dose on Cycle 2 Day 1
Secondary	Number of Participants With Anti-Drug Antibody (ADA) Against Tremelimumab	Blood samples (approximately 5 mL) to provide at least 1 mL of serum to detect ADA were collected from participants enrolled in to Cohorts 3A to 9A and Cohorts 1B to 5B. Participants were considered ADA-positive if sample titer (log10) >=1.48; participants were considered ADA-negative if sample titer (log10) <1.48.	Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to tremelimumab dosing.
Secondary	Titer of Treatment-Induced ADA Against Tremelimumab	Treatment-induced ADA was defined as baseline titer missing or negative and participant had >=1 post-treatment positive titer. Blood samples (approximately 5 mL) to provide at least 1 mL of serum to detect ADA were collected from participants enrolled in to Cohorts 3A to 9A and Cohorts 1B to 5B.	Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to tremelimumab dosing.
Secondary	Number of Participants With Neutralizing Antibody (NAb) Against Tremelimumab	Only those samples tested positive for ADA were to be further tested for Nab. Blood samples (approximately 5 mL) to provide at least 1 mL of serum to detect NAb were collected from participants enrolled in to Cohorts 3A to 9A and Cohorts 1B to 5B. Nab against tremelimumab was not examined due to business reason.	Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to tremelimumab dosing.
Secondary	Titer of Treatment-Induced NAb Against Tremelimumab	Only those samples tested positive for ADA were to be further tested for Nab. Blood samples (approximately 5 mL) to provide at least 1 mL of serum to detect NAb were collected from participants enrolled in to Cohorts 3A to 9A and Cohorts 1B to 5B. Nab against tremelimumab was not examined due to business reason.	Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to tremelimumab dosing.
Secondary	Number of Participants With ADA Against PF-06801591	Participants were considered ADA-positive if sample titer (log10) >=99; Participants were considered ADA-negative if sample titer (log10) <99. Blood samples (approximately 5 mL) to provide at least 1 mL of serum for detection of ADA against PF-06801591 were collected from participants enrolled in Cohorts 6A to 9A and Cohorts 3B and 5B.	Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to PF-06801591 dosing.
Secondary	Titer of Treatment-Induced ADA Against PF-06801591	Treatment-induced ADA was defined as baseline titer missing or negative and participant had >=1 post-treatment positive titer. Blood samples (approximately 5 mL) to provide at least 1 mL of serum for detection of ADA against PF-06801591 were collected from participants enrolled in Cohorts 6A to 9A and Cohorts 3B and 5B.	Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to PF-06801591 dosing.
Secondary	Number of Participants With NAb Against PF-06801591	Only those samples tested positive for ADA were to be further tested for Nab. Blood samples (approximately 5 mL) to provide at least 1 mL of serum for detection of NAb against PF-06801591 were collected from participants enrolled in Cohorts 6A to 9A and Cohorts 3B and 5B. Nab against PF-06801591 was not examined due to business reason.	Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to PF-06801591 dosing.
Secondary	Titer of Treatment-Induced NAb Against PF-06801591	Only those samples tested positive for ADA were to be further tested for Nab. Blood samples (approximately 5 mL) to provide at least 1 mL of serum for detection of NAb against PF-06801591 were collected from participants enrolled in Cohorts 6A to 9A and Cohorts 3B and 5B. Nab against PF-06801591 was not examined due to business reason.	Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to PF-06801591 dosing.
Secondary	Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Cohort 7A and 3B Combined and All mCRPC Patients	ORR was defined as the percentage of participants with best overall response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST v1.1. Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm) and no new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease and no new lesions.	Baseline up to 6 months after EOT (52 months in maximum)
Secondary	Duration of Response (DOR) by RECIST v1.1 in Cohort 7A and 3B Combined and All mCRPC Patients	DOR was defined as the time from first documentation of confirmed CR or PR to date of first documentation of progressive disease (PD) or death due to any cause according to RECIST v1.1. Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm) and no new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all measurable target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease and no new lesions. PD was defined as >=20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm. Unequivocal progression of pre existing lesions for non-target disease.	Baseline up to 6 months after EOT (52 months in maximum)
Secondary	Immune-Related Confirmed ORR by Immune Related Response Evaluation Criteria in Solid Tumors Version 1.1 (irRECIST v1.1) in Cohort 7A and 3B Combined and All mCRPC Patients	Immune-related confirmed ORR was defined as the percentage of participants with objective response based assessment of confirmed immune related complete response (irCR) or confirmed immune related partial response (irPR) according to irRECIST v1.1. Per irRECIST v1.1: irCR was defined as complete disappearance of all lesions and no new lesions. All measurable lymph nodes also must have a reduction in short axis to <10 mm. irPR was defined as sum of the diameters (longest for non nodal lesions, shortest for nodal lesions) of target and new measurable lesions must decrease >=30%.	Baseline up to 6 months after EOT (52 months in maximum)
Secondary	Immune-Related Confirmed DOR by irRECIST v1.1 in Cohort 7A and 3B Combined and All mCRPC Patients	Immune-related confirmed DOR was defined as the time from first documentation of confirmed irCR or confirmed irPR to date of first documentation of immune related progressive disease (irPD) or death due to any cause according to irRECIST. Per irRECIST v1.1: irCR was defined as complete disappearance of all lesions and no new lesions. All measurable lymph nodes also must have a reduction in short axis to <10 mm. irPR was defined as sum of the diameters (longest for non nodal lesions, shortest for nodal lesions) of target and new measurable lesions must decrease >=30%. irPD was defined as sum of the diameters of target and new measurable lesions must increase >=20%, confirmed by a repeat, consecutive observation at least 4 weeks from the date first documented.	Baseline up to 6 months after EOT (52 months in maximum)
Secondary	Number of Patients With Bone Progression Per Prostrate Cancer Working Group 3 (PCWG3) Criteria in Cohort 7A and 3B Combined	Number of participants with bone progression per Prostate Cancer Clinical Trials Working Group 3 (PCWG3). Per PCWG3, progressing disease on bone scan was considered when at least two new lesions relative to the first post treatment scan was confirmed on a subsequent scan (6 or more weeks later).	Baseline up to 6 months after EOT (52 months in maximum)
Secondary	Radiographic Progression Free Survival (rPFS) Per RECIST v1.1 in Cohort 7A and 3B Combined , All mCRPC Patients, Cohort 1B, and Cohort 5B	Radiographic Progression Free Survival (rPFS) per RECIST v1.1. rPFS was defined as the time from first dose of study treatment to date of first documentation of radiographic PD or death due to any cause, whichever occurs first. Per RECIST v1.1, PD was defined as >=20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm. Unequivocal progression of pre existing lesions for non-target disease. The Kaplan Meier estimate of median rPFS was presented here.	Baseline up to 6 months after EOT (52 months in maximum)
Secondary	Number of Participants Achieving Central PSA Response >= 50% Decline From Baseline (PSA-50) in Part B	PSA-50 response rate was defined as the proportion of patients whose on-study PSA declined from baseline by at least 50% at two consecutive measurements at least 3 weeks apart, prior to other systematic anti-cancer therapy.	At screening; Cycle 1 and 2: at Day 1, Day 29, Day 57, and Day 85; at the EOT visit, and 1, 2, 4 and 6 months after EOT.
Secondary	Duration of PSA-50 Response in Part B	Duration of PSA-50 response was defined as the period from the first measurement when PSA-50 response was achieved to the measurement when PSA-50 response no longer held.	Days 1, 29, 57 of Cycle 1 and Cycle 2.
Secondary	Baseline for PSA in Part B	PSA Baseline is defined as the most recent non-missing value prior to dosing.	At screening and Cycle 1 Day 1.
Secondary	Baseline for PSA Doubling Time (PSADT) in Part B	PSADT was defined as the natural log of 2 divided by the slope of the linear regression line of the natural log of PSA against time in month. Baseline has been calculated from the PSA values at screening and C1D1.	At screening and Cycle 1 Day 1.
Secondary	Baseline for PSA Slope in Part B	PSA slope was defined as the slope of the linear regression line of natural log of PSA against time in month. Baseline has been calculated from the PSA values at screening and C1D1.	At screening and Cycle 1 Day 1.
Secondary	Baseline for PSA Velocity in Part B	PSA velocity was defined as the slope of the linear regression line of PSA against time in month. Baseline has been calculated from the PSA values at screening and C1D1.	At screening and Cycle 1 Day 1.
Secondary	Change in PSADT at Post-Treatment Visit From Baseline in Part B	PSADT was defined as the natural log of 2 divided by the slope of the linear regression line of the natural log of PSA against time in month. PSADT at the post-treatment visit was calculated from C1D1 and all post-treatment PSA values.	At screening; Cycle 1 and 2: at Day 1, Day 29, Day 57, and Day 85; at the EOT visit, and 1, 2, 4 and 6 months after EOT.
Secondary	Change in PSA Slope at Post-Treatment Visit From Baseline in Part B	PSA slope was defined as the slope of the linear regression line of natural log of PSA against time in month. PSA slope at the post-treatment visit was calculated from C1D1 and all post-treatment PSA values.	At screening; Cycle 1 and 2: at Day 1, Day 29, Day 57, and Day 85; at the EOT visit, and 1, 2, 4 and 6 months after EOT.
Secondary	Change in PSA Velocity at Post-Treatment Visit From Baseline in Part B	PSA velocity was defined as the slope of the linear regression line of PSA against time in month. PSA velocity at the post-treatment visit was calculated from C1D1 and all post-treatment PSA values.	At screening; Cycle 1 and 2: at Day 1, Day 29, Day 57, and Day 85; at the EOT visit, and 1, 2, 4 and 6 months after EOT.

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