Clinical trial NCT02616185: A Phase 1 Study To Evaluate Escalating Doses Of A Vaccine-Based Immunotherapy Regimen For Prostate Cancer (PrCa VBIR)
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Prostatic Neoplasms
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2015-11-26
Enrollment: 91
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 6 months after End of Treatment (EOT; 52 months in maximum)
measure: 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)
timeFrame: Baseline up to 6 months after EOT (52 months in maximum)
measure: Number of Participants With AEs Leading to Discontinuation or Dose Reduction
timeFrame: Baseline up to 6 months after EOT (52 months in maximum)
measure: Number of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: The first 28 days following the first AdC68 vaccination (on Cycle 1 Day 1)
Secondary outcomes:
measure: Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4)
timeFrame: Baseline up to 6 months after EOT (52 months in maximum)
measure: Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4)
timeFrame: Baseline up to 6 months after EOT (52 months in maximum)
measure: Number of Participants With Laboratory Abnormalities in Urinalysis (Grade 3 or 4)
timeFrame: Baseline up to 6 months after EOT (52 months in maximum)
measure: Change From Baseline in T Cell Response to Prostate Specific Antigen (PSA) in Part A
timeFrame: 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.
measure: Change From Baseline in T Cell Response to Prostate Stem Cell Antigen (PSCA) in Part A
timeFrame: 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.
measure: Change From Baseline in T Cell Response to Prostate Specific Membrane Antigen (PSMA) in Part A
timeFrame: 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.
measure: Maximum Observed Plasma Concentration (Cmax) of Tremelimumab in Part A
timeFrame: 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.
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tremelimumab in Part A
timeFrame: 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.
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Tremelimumab in Part A
timeFrame: 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.
measure: Trough Concentrations (Ctrough) After Multiple Dosing of Tremelimumab
timeFrame: Pre-dose on Cycle 2 Day 1
measure: Cmax of PF-06801591 in Part A
timeFrame: 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.
measure: Tmax of PF-06801591 in Part A
timeFrame: 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.
measure: AUClast of PF-06801591 in Part A
timeFrame: 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.
measure: Ctrough of PF-06801591
timeFrame: Pre-dose on Cycle 2 Day 1
measure: Number of Participants With Anti-Drug Antibody (ADA) Against Tremelimumab
timeFrame: 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.
measure: Titer of Treatment-Induced ADA Against Tremelimumab
timeFrame: 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.
measure: Number of Participants With Neutralizing Antibody (NAb) Against Tremelimumab
timeFrame: 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.
measure: Titer of Treatment-Induced NAb Against Tremelimumab
timeFrame: 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.
measure: Number of Participants With ADA Against PF-06801591
timeFrame: 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.
measure: Titer of Treatment-Induced ADA Against PF-06801591
timeFrame: 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.
measure: Number of Participants With NAb Against PF-06801591
timeFrame: 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.
measure: Titer of Treatment-Induced NAb Against PF-06801591
timeFrame: 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.
measure: 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
timeFrame: Baseline up to 6 months after EOT (52 months in maximum)
measure: Duration of Response (DOR) by RECIST v1.1 in Cohort 7A and 3B Combined and All mCRPC Patients
timeFrame: Baseline up to 6 months after EOT (52 months in maximum)
measure: 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
timeFrame: Baseline up to 6 months after EOT (52 months in maximum)
measure: Immune-Related Confirmed DOR by irRECIST v1.1 in Cohort 7A and 3B Combined and All mCRPC Patients
timeFrame: Baseline up to 6 months after EOT (52 months in maximum)
measure: Number of Patients With Bone Progression Per Prostrate Cancer Working Group 3 (PCWG3) Criteria in Cohort 7A and 3B Combined
timeFrame: Baseline up to 6 months after EOT (52 months in maximum)
measure: Radiographic Progression Free Survival (rPFS) Per RECIST v1.1 in Cohort 7A and 3B Combined , All mCRPC Patients, Cohort 1B, and Cohort 5B
timeFrame: Baseline up to 6 months after EOT (52 months in maximum)
measure: Number of Participants Achieving Central PSA Response >= 50% Decline From Baseline (PSA-50) in Part B
timeFrame: 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.
measure: Duration of PSA-50 Response in Part B
timeFrame: Days 1, 29, 57 of Cycle 1 and Cycle 2.
measure: Baseline for PSA in Part B
timeFrame: At screening and Cycle 1 Day 1.
measure: Baseline for PSA Doubling Time (PSADT) in Part B
timeFrame: At screening and Cycle 1 Day 1.
measure: Baseline for PSA Slope in Part B
timeFrame: At screening and Cycle 1 Day 1.
measure: Baseline for PSA Velocity in Part B
timeFrame: At screening and Cycle 1 Day 1.
measure: Change in PSADT at Post-Treatment Visit From Baseline in Part B
timeFrame: 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.
measure: Change in PSA Slope at Post-Treatment Visit From Baseline in Part B
timeFrame: 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.
measure: Change in PSA Velocity at Post-Treatment Visit From Baseline in Part B
timeFrame: 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.
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Banner-University Medical Center Tucson
state: Arizona
city: Tucson
country: United States
facility: The University of Arizona Cancer Center-North Campus
state: Arizona
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale-New Haven
state: Connecticut
city: New Haven
country: United States
facility: Smilow Cancer Hospital Phase 1 Unit
state: Connecticut
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
city: Omaha
country: United States
facility: GU Research Network
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Morristown
country: United States
facility: Garden State Urology
state: New Jersey
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: Rockaway
country: United States
facility: Garden State Urology
state: New Jersey
city: Whippany
country: United States
facility: Garden State Urology
state: New Jersey
city: Lake Success
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center 53rd Street
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center, Sidney Kimmel Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: