Back to resultsPLX2853 in Combination With Abiraterone Acetate and Prednisone and in Combination With Olaparib in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Primary Purpose
Metastatic Castration-resistant Prostate Cancer
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
PLX2853
Olaparib
Abiraterone acetate
Prednisone
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Castration-resistant Prostate Cancer focused on measuring PLX2853, Metastatic Castration-resistant Prostate Cancer, Olaparib, Abiraterone Acetate, Adenocarcinoma, Prostate Cancer
Eligibility Criteria
Inclusion Criteria:
- Age ≥18 years at the time of signing informed consent.
- Histologically confirmed adenocarcinoma of the prostate with tumor tissue available for molecular analyses.
- Eastern Cooperative Oncology Group Performance Status 0 to 1.
- Adequate organ function as demonstrated following laboratory values.
- Fertile male subjects with female sexual partners must agree to use a highly effective method of birth control during the study and for 90 days after the last dose of study drug.
- Except as specified above for organ function, all drug-related toxicity from previous cancer therapy (including ongoing Abiraterone Acetate + Prednisone therapy if applicable) must be resolved (to Grade ≤1 or baseline per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0) prior to study treatment administration (Grade 2: alopecia, hot flashes, decreased libido, or neuropathy is allowed).
- Willingness and ability to provide written informed consent prior to any study-related procedures and to comply with all study requirements.
Exclusion Criteria:
- Prior exposure to a bromodomain inhibitor.
- History of autoimmune hemolytic anemia or autoimmune thrombocytopenia.
- Clinically significant cardiac disease.
- Inability to take oral medication or significant nausea and vomiting, malabsorption, or significant small bowel resection that, in the opinion of the Investigator, would preclude adequate absorption.
Active known second malignancy with the exception of any of the following:
- Adequately treated basal cell carcinoma or squamous cell carcinoma of the skin.
- Adequately treated Stage I cancer from which the subject is currently in remission and has been in remission for ≥2 years.
- Any other cancer from which the subject has been disease-free for ≥3 years.
- Subject is participating in any other therapeutic clinical study (observational or registry studies are allowed).
- Presence of any other medical, psychological, familial, sociological, or geographic condition potentially hampering compliance with the study protocol or would interfere with the study endpoints or the subject's ability to participate in the study in the judgment of the Investigator.
- Receipt of any anti-cancer therapy prior to Cycle 1 Day 1 with less than protocol defined wash-out with the exception of Abiraterone Acetate (for subjects enrolling into Abiraterone Acetate Combination) and GnRH therapy.
Sites / Locations
- University of Chicago
- Karmanos Cancer Institute
- Columbia University Medical Center
- Carolina Urologic Research Center
- Tennessee Oncology/ Sarah Cannon
- Virginia Cancer Specialist
- University of Wisconsin
- Sarah Cannon Research Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
PLX2853 + Abiraterone Acetate + Prednisone
PLX2853 + Olaparib
Arm Description
Phase 1b (PLX2853 + Abiraterone Acetate + Prednisone Combination): Up to 15 evaluable subjects with mCRPC will be enrolled. Phase 2a (PLX2853 + Abiraterone Acetate + Prednisone Combination): Up to 19 evaluable subjects with mCRPC will be enrolled.
Phase 1b (PLX2853 + Olaparib Combination): Up to 18 evaluable subjects with homologous recombination repair (HRR) gene-mutated mCRPC will be enrolled. Phase 2a (PLX2853 + Olaparib Combination): Up to 58 evaluable subjects with homologous recombination repair (HRR) gene-mutated mCRPC will be enrolled.
Outcomes
Primary Outcome Measures
Phase 2a (both arms): Disease response as defined by at least one of the following: Objective response by modified RECIST v1.1, PSA response, or circulating tumor cell count (CTC) response.
Phase 1b (both arms): Incidence of dose-limiting-toxicities (DLTs)
Phase 1b (both arms): Incidence of TEAEs that are related to treatment
Secondary Outcome Measures
Radiographic progression-free survival (rPFS) (both arms, both phases)
Radiographic progression-free survival (PFS) will be calculated for each subject as the number of days from the first day of PLX2853 and combination agent(s) treatment (Cycle 1 Day 1) to the date of the first documented disease progression by either RECIST v.1.1 or on bone scan.
Time to PSA Progression (both arms, both phases)
PSA progression (defined per PCWG3 as a ≥25% increase and an absolute increase of ≥2 ng/mL above the nadir, which is confirmed by a second consecutive value obtained 3 or more weeks later).
Duration of PSA Response (both arms, both phases)
Duration of PSA response will be calculated for each subject with a PSA response as the time from date of first documented, confirmed response (CR or PR) using PCWG3 until date of documented progression confirmed at least 3 weeks later, or death from any cause.
Overall Survival (OS) (both arms, both phases)
Overall survival (OS) will be calculated for each subject as the number of days from the first day of PLX2853 treatment and combination agent(s) (Cycle 1 Day 1) to the date of death from any cause. If a subject is lost to follow-up, OS is censored at the date of last contact.
Incidence of all TEAEs (both arms, both phases)
Incidence of TEAEs that result in dose interruption, reduction or discontinuation (both arms, both phases)
PLX2853 PK parameter AUC0-24 (both arms, both phases)
AUC from time zero extrapolated to 24 hours (AUC0-24)
PLX2853 PK parameter Cmax (both arms, both phases)
Maximum observed concentration
PLX2853 PK parameter T1/2 (both arms, both phases)
terminal elimination half-life (T1/2)
Best Overall Response (BOR) (both arms, both phases)
Best Overall Response (BOR) per RECIST v1.1 will be calculated for each subject with a minimum interval for confirmation of CR and PR of 4 weeks.
Duration of Response (DOR) (both arms, both phases)
Time from date of first documented, confirmed response using RECIST v1.1 and PCWG3 until date of documented progression or death from any cause.
Time to first Symptomatic Skeletal-Related Event (SSRE) (both arms, both phases)
Time to first Symptomatic Skeletal-Related Event (SSRE) defined as:
Use of radiation therapy to prevent or relieve skeletal symptoms.
Occurrence of new symptomatic pathological bone fractures (vertebral or non-vertebral). Radiologic documentation is required.
Occurrence of spinal cord compression. Radiologic documentation required.
Orthopedic surgical intervention for bone metastasis.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04556617
Brief Title
PLX2853 in Combination With Abiraterone Acetate and Prednisone and in Combination With Olaparib in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Official Title
A Multicenter, Open-Label, Parallel, Phase 1b/2a Study of PLX2853 in Combination With Abiraterone Acetate and Prednisone and Phase 1b/2a Study of PLX2853 in Combination With Olaparib in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Terminated
Why Stopped
study terminated due to business realignment
Study Start Date
September 21, 2020 (Actual)
Primary Completion Date
May 24, 2022 (Actual)
Study Completion Date
May 24, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Opna-IO LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this research study is to evaluate safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of the investigational drug PLX2853 in subjects with Metastatic Castration-Resistant Prostate Cancer (mCRPC)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Castration-resistant Prostate Cancer
Keywords
PLX2853, Metastatic Castration-resistant Prostate Cancer, Olaparib, Abiraterone Acetate, Adenocarcinoma, Prostate Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PLX2853 + Abiraterone Acetate + Prednisone
Arm Type
Experimental
Arm Description
Phase 1b (PLX2853 + Abiraterone Acetate + Prednisone Combination): Up to 15 evaluable subjects with mCRPC will be enrolled.
Phase 2a (PLX2853 + Abiraterone Acetate + Prednisone Combination): Up to 19 evaluable subjects with mCRPC will be enrolled.
Arm Title
PLX2853 + Olaparib
Arm Type
Experimental
Arm Description
Phase 1b (PLX2853 + Olaparib Combination): Up to 18 evaluable subjects with homologous recombination repair (HRR) gene-mutated mCRPC will be enrolled.
Phase 2a (PLX2853 + Olaparib Combination): Up to 58 evaluable subjects with homologous recombination repair (HRR) gene-mutated mCRPC will be enrolled.
Intervention Type
Drug
Intervention Name(s)
PLX2853
Intervention Description
PLX2853 tablets
Intervention Type
Drug
Intervention Name(s)
Olaparib
Intervention Description
Olaparib tablets
Intervention Type
Drug
Intervention Name(s)
Abiraterone acetate
Intervention Description
Abiraterone acetate tablets
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Prednisone (or equivalent) tablets
Primary Outcome Measure Information:
Title
Phase 2a (both arms): Disease response as defined by at least one of the following: Objective response by modified RECIST v1.1, PSA response, or circulating tumor cell count (CTC) response.
Time Frame
From 6 weeks of treatment (Cycle 3 Day 1; 21 days per cycle) until completion of long term follow-up, an average of 6 months.
Title
Phase 1b (both arms): Incidence of dose-limiting-toxicities (DLTs)
Time Frame
From time of first dose of PLX2853 and combination agent(s) through completion of Cycle 1 (21 days).
Title
Phase 1b (both arms): Incidence of TEAEs that are related to treatment
Time Frame
From time of first dose of PLX2853 and combination agent(s) until 30 days from end of treatment.
Secondary Outcome Measure Information:
Title
Radiographic progression-free survival (rPFS) (both arms, both phases)
Description
Radiographic progression-free survival (PFS) will be calculated for each subject as the number of days from the first day of PLX2853 and combination agent(s) treatment (Cycle 1 Day 1) to the date of the first documented disease progression by either RECIST v.1.1 or on bone scan.
Time Frame
From 6 weeks of treatment (Cycle 3 Day 1; 21 days per cycle) until completion of long term follow-up, an average of 6 months.
Title
Time to PSA Progression (both arms, both phases)
Description
PSA progression (defined per PCWG3 as a ≥25% increase and an absolute increase of ≥2 ng/mL above the nadir, which is confirmed by a second consecutive value obtained 3 or more weeks later).
Time Frame
From 3 weeks of treatment (Cycle 2 Day 1; 21 days per cycle) until completion of long term follow-up, an average of 6 months.
Title
Duration of PSA Response (both arms, both phases)
Description
Duration of PSA response will be calculated for each subject with a PSA response as the time from date of first documented, confirmed response (CR or PR) using PCWG3 until date of documented progression confirmed at least 3 weeks later, or death from any cause.
Time Frame
From 3 weeks of treatment (Cycle 3 Day 1; 21 days per cycle) until completion of long term follow-up, an average of 6 months.
Title
Overall Survival (OS) (both arms, both phases)
Description
Overall survival (OS) will be calculated for each subject as the number of days from the first day of PLX2853 treatment and combination agent(s) (Cycle 1 Day 1) to the date of death from any cause. If a subject is lost to follow-up, OS is censored at the date of last contact.
Time Frame
From time of first dose until completion of long term follow-up, approximately 30 months.
Title
Incidence of all TEAEs (both arms, both phases)
Time Frame
From time of first dose of PLX2853 and combination agent(s) until 30 days from end of treatment.
Title
Incidence of TEAEs that result in dose interruption, reduction or discontinuation (both arms, both phases)
Time Frame
From time of first dose of PLX2853 and combination agent(s) until 30 days from end of treatment.
Title
PLX2853 PK parameter AUC0-24 (both arms, both phases)
Description
AUC from time zero extrapolated to 24 hours (AUC0-24)
Time Frame
From time of first dose until 30 days from end of treatment.
Title
PLX2853 PK parameter Cmax (both arms, both phases)
Description
Maximum observed concentration
Time Frame
From time of first dose until 30 days from end of treatment.
Title
PLX2853 PK parameter T1/2 (both arms, both phases)
Description
terminal elimination half-life (T1/2)
Time Frame
From time of first dose until 30 days from end of treatment.
Title
Best Overall Response (BOR) (both arms, both phases)
Description
Best Overall Response (BOR) per RECIST v1.1 will be calculated for each subject with a minimum interval for confirmation of CR and PR of 4 weeks.
Time Frame
From 6 weeks of treatment (Cycle 3 Day 1; 21 days per cycle) until completion of long term follow-up, an average of 6 months.
Title
Duration of Response (DOR) (both arms, both phases)
Description
Time from date of first documented, confirmed response using RECIST v1.1 and PCWG3 until date of documented progression or death from any cause.
Time Frame
From 6 weeks of treatment (Cycle 3 Day 1; 21 days per cycle) until completion of long term follow-up, an average of 6 months.
Title
Time to first Symptomatic Skeletal-Related Event (SSRE) (both arms, both phases)
Description
Time to first Symptomatic Skeletal-Related Event (SSRE) defined as:
Use of radiation therapy to prevent or relieve skeletal symptoms.
Occurrence of new symptomatic pathological bone fractures (vertebral or non-vertebral). Radiologic documentation is required.
Occurrence of spinal cord compression. Radiologic documentation required.
Orthopedic surgical intervention for bone metastasis.
Time Frame
From time of first dose until 30 days from end of treatment.
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥18 years at the time of signing informed consent.
Histologically confirmed adenocarcinoma of the prostate with tumor tissue available for molecular analyses.
Eastern Cooperative Oncology Group Performance Status 0 to 1.
Adequate organ function as demonstrated following laboratory values.
Fertile male subjects with female sexual partners must agree to use a highly effective method of birth control during the study and for 90 days after the last dose of study drug.
Except as specified above for organ function, all drug-related toxicity from previous cancer therapy (including ongoing Abiraterone Acetate + Prednisone therapy if applicable) must be resolved (to Grade ≤1 or baseline per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0) prior to study treatment administration (Grade 2: alopecia, hot flashes, decreased libido, or neuropathy is allowed).
Willingness and ability to provide written informed consent prior to any study-related procedures and to comply with all study requirements.
Exclusion Criteria:
Prior exposure to a bromodomain inhibitor.
History of autoimmune hemolytic anemia or autoimmune thrombocytopenia.
Clinically significant cardiac disease.
Inability to take oral medication or significant nausea and vomiting, malabsorption, or significant small bowel resection that, in the opinion of the Investigator, would preclude adequate absorption.
Active known second malignancy with the exception of any of the following:
Adequately treated basal cell carcinoma or squamous cell carcinoma of the skin.
Adequately treated Stage I cancer from which the subject is currently in remission and has been in remission for ≥2 years.
Any other cancer from which the subject has been disease-free for ≥3 years.
Subject is participating in any other therapeutic clinical study (observational or registry studies are allowed).
Presence of any other medical, psychological, familial, sociological, or geographic condition potentially hampering compliance with the study protocol or would interfere with the study endpoints or the subject's ability to participate in the study in the judgment of the Investigator.
Receipt of any anti-cancer therapy prior to Cycle 1 Day 1 with less than protocol defined wash-out with the exception of Abiraterone Acetate (for subjects enrolling into Abiraterone Acetate Combination) and GnRH therapy.
Facility Information:
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Carolina Urologic Research Center
City
Myrtle Beach
State/Province
South Carolina
ZIP/Postal Code
29572
Country
United States
Facility Name
Tennessee Oncology/ Sarah Cannon
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Virginia Cancer Specialist
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
University of Wisconsin
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Sarah Cannon Research Institute
City
London
ZIP/Postal Code
W1G 6AD
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
PLX2853 in Combination With Abiraterone Acetate and Prednisone and in Combination With Olaparib in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
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