Back to resultsTreatment of Metastatic Castration-Resistant Prostate Cancer With Homologous Recombination Deficiency
Primary Purpose
Metastatic Castration-Resistant Prostate Cancer (mCRPC), Homologous Recombination Deficiency (HRD)
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Pamiparib
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Eligibility Criteria
Key Inclusion Criteria:
- Men (≥ 18 years of age) with histologically or cytologically confirmed adenocarcinoma or poorly differentiated adenocarcinoma of the prostate without neuroendocrine differentiation with HRD deficiency by CTC-HRD assay and/or deleterious germline or somatic mutation in BRCA1 or BRCA2; mCRPC measurable disease and/or bone disease. • PSA progression with ≥ 3 rising PSA levels with ≥ 1 week between determinations and a screening PSA ≥ 2 μg/L (2 ng/mL).
- Must be surgically or medically castrated with serum testosterone levels of ≤1.73 nmol/L (50 ng/dL), must have received ≥ 1 prior androgen receptor-targeted therapy, and must have received ≥ 1 taxane-based therapy.
- mCRPC with 1 or 2 of the following:
- Measurable disease per RECIST v1.1
- Bone disease
- CTC-HRD+ or BRCA1/2 mutation
- PSA progression (PCWG3 criteria)
- ≥1 androgen receptor-targeted therapy (eg, abiraterone acetate/prednisone or enzalutamide) for mCRPC with progressive disease
- ≥1 taxane for metastatic prostate cancer
Key Exclusion Criteria:
- Chemotherapy, hormonal therapy, biologic therapy, radionuclide therapy, immunotherapy, investigational agent, anticancer Chinese medicine, or herbal remedies ≤ 5 half-lives if the half-life is known, ≤ 14 days if not known, before start of study treatment
- Continued treatment with a bisphosphonate or denosumab is allowed, if administered at a stable dose > 28 days before start of study treatment
- Radiotherapy ≤ 21 days (≤ 14 days, if single fraction of radiotherapy) before start of study treatment
Prior treatment for prostate cancer with any of the following:
- poly ADP ribose polymerase (PARP) inhibitor
- Platinum
- Cyclophosphamide
- Mitoxantrone
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Sites / Locations
- University Cancer and Blood Center
- Montefiore Einstein Cancer Center
- University of Washington
- Gosford Hospital
- Liverpool Hospital
- Calvary Mater Newcastle
- Icon Cancer Care Foundation
- Pan American Oncology Trials, LLC
- L Hospitalet de Llobregat
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Pamiparib
Arm Description
Participants will receive pamiparib for a period up to 1 year
Outcomes
Primary Outcome Measures
Objective Response Rate (ORR) Determined by Independent Review Committee
ORR is the percentage of participants with a best objective response of complete response (CR) or partial response (PR) confirmed at a subsequent timepoint ≥ 4 weeks later by an Independent Review Committee (IRC).
Prostate-Specific Antigen (PSA) Response Rate
PSA response rate is defined as the percentage of participants with PSA decline ≥ 50% from baseline [confirmed by a second PSA value ≥ 3 weeks later] for CTC-HRD-positive participants with or without measurable disease.
Secondary Outcome Measures
Duration of Response (DOR) by IRC
DOR is defined as the time from the date of the earliest documented CR or PR (that is subsequently confirmed) to radiographic disease progression or death due to any cause, whichever occurs first.
Objective Response Rate by Investigator
ORR is the percentage of participants with a best objective response of complete response (CR) or partial response (PR) confirmed at a subsequent timepoint ≥ 4 weeks later by the investigator.
Time to Objective Response by Investigator
Time to objective response is defined as the time from the date of the first dose of study drug to the first documented confirmed response of CR or PR assessed by the investigator and summarized for participants who have achieved a confirmed objective response.
Clinical Benefit Rate By Investigator
Clinical Benefit Rate is the percentage of participants who achieved confirmed CR, PR, or SD or NON-CR/NON-PD. The minimum interval for confirmed CR and PR is 4 weeks and the measurement of SD or NON-CR/NON-PD is 7 weeks after first dose date.
Time to PSA Response
Time to PSA response is defined as the time from the date of the first dose of study drug to the first PSA decline ≥ 50% that is subsequently confirmed. Assessments are summarized for participants who have achieved a confirmed PSA response.
Duration of PSA Response
Duration of PSA response is defined as the time from the date of the earliest documented PSA response (that is subsequently confirmed) to PSA progression or death due to any cause, whichever occurs first. PSA progression is defined as a ≥ 25% increase in PSA with an absolute increase of ≥ 2 μg/L above the nadir (or above the baseline for participants with no PSA decline) after12 weeks, confirmed by a second value ≥ 3 weeks later. The nadir is defined as the lowest value at or after baseline.
Time to PSA Progression
Time to PSA progression is defined as the time from the date of the first dose of study drug to a ≥ 25% increase in PSA with an absolute increase of ≥ 2 ng/mL above the nadir (or above the baseline for participants with no PSA decline) after 12 weeks, confirmed by a second value ≥ 3 weeks later. Death for the participants with no PSA progression is also considered as an event.
Time to Symptomatic Skeletal Event
Time to symptomatic skeletal event (SSE) is defined as time from the date of the first dose of study drug to the first symptomatic fracture, radiation or surgery to bone, or spinal cord compression.
Radiographic Progression-Free Survival by IRC
Radiographic progression-free survival is defined as the time from the date of the first dose of study drug to radiographic disease progression by IRC or death due to any cause, whichever occurs first.
Overall Survival (OS)
Overall survival is defined as the time from the date of the first dose of study drug to death due to any cause.
Number of Participants With Treatment-Emergent Adverse Events Graded According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03712930
Brief Title
Treatment of Metastatic Castration-Resistant Prostate Cancer With Homologous Recombination Deficiency
Official Title
A Phase 2, Open-Label, Single-Arm Study of BGB-290 (BGB-290) for the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC) With Homologous Recombination Deficiency (HRD)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Terminated
Why Stopped
Sponsor's decision to revisit the development approach for prostate cancer.
Study Start Date
February 5, 2019 (Actual)
Primary Completion Date
August 6, 2020 (Actual)
Study Completion Date
September 2, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BeiGene
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This study is designed to evaluate the efficacy of pamiparib in participants with metastatic castration-resistant prostate cancer (mCRPC) positive for circulating tumor cells (CTC) with homologous recombination deficiency (CTC-HRD). All participants will receive pamiparib. The purpose of this study is to demonstrate that pamiparib will improve Objective Response Rate (ORR) and Prostate-Specific Antigen (PSA) response rate
Detailed Description
This is a global, Phase 2, open-label study of pamiparib in approximately 100 participants with metastatic castration-resistant prostate cancer (mCRPC) positive for circulating tumor cells (CTC) with homologous recombination deficiency (CTC-HRD). Participants in Cohort 1 will include 50 mCRPC participants with CTC-HRD-positive, measurable metastatic disease (soft tissue with/without bone lesions), and positive BRCA1/2 mutation or negative/unknown BRCA1/2 mutation. Cohort 2 will include 30 mCRPC CTC-HRD positive participants with bone metastasis only and positive or negative/unknown BRCA1/2. Cohort 3 and 4 will include 20 mCRPC CTC-HRD negative/unknown participants with BRCA1/2 positive mutations, metastatic disease (measurable soft tissue with/without bone), and bone only. Participants will undergo PSA level assessments approximately every 4 weeks as well as tumor assessments every 8 weeks for 24 weeks and the every 12 weeks, or as clinically indicated. Administration of pamiparib will continue until disease progression, unacceptable toxicity, death or another discontinuation criterion is met.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Castration-Resistant Prostate Cancer (mCRPC), Homologous Recombination Deficiency (HRD)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pamiparib
Arm Type
Experimental
Arm Description
Participants will receive pamiparib for a period up to 1 year
Intervention Type
Drug
Intervention Name(s)
Pamiparib
Other Intervention Name(s)
BGB-290
Intervention Description
60 mg orally twice daily (BID)
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR) Determined by Independent Review Committee
Description
ORR is the percentage of participants with a best objective response of complete response (CR) or partial response (PR) confirmed at a subsequent timepoint ≥ 4 weeks later by an Independent Review Committee (IRC).
Time Frame
Up to 1 year and 6 months
Title
Prostate-Specific Antigen (PSA) Response Rate
Description
PSA response rate is defined as the percentage of participants with PSA decline ≥ 50% from baseline [confirmed by a second PSA value ≥ 3 weeks later] for CTC-HRD-positive participants with or without measurable disease.
Time Frame
Up to 1 year and 6 months
Secondary Outcome Measure Information:
Title
Duration of Response (DOR) by IRC
Description
DOR is defined as the time from the date of the earliest documented CR or PR (that is subsequently confirmed) to radiographic disease progression or death due to any cause, whichever occurs first.
Time Frame
Up to 1 year and 7 months
Title
Objective Response Rate by Investigator
Description
ORR is the percentage of participants with a best objective response of complete response (CR) or partial response (PR) confirmed at a subsequent timepoint ≥ 4 weeks later by the investigator.
Time Frame
Up to 1 year and 6 months
Title
Time to Objective Response by Investigator
Description
Time to objective response is defined as the time from the date of the first dose of study drug to the first documented confirmed response of CR or PR assessed by the investigator and summarized for participants who have achieved a confirmed objective response.
Time Frame
Up to 1 year and 6 months
Title
Clinical Benefit Rate By Investigator
Description
Clinical Benefit Rate is the percentage of participants who achieved confirmed CR, PR, or SD or NON-CR/NON-PD. The minimum interval for confirmed CR and PR is 4 weeks and the measurement of SD or NON-CR/NON-PD is 7 weeks after first dose date.
Time Frame
Up to 1 year and 6 months
Title
Time to PSA Response
Description
Time to PSA response is defined as the time from the date of the first dose of study drug to the first PSA decline ≥ 50% that is subsequently confirmed. Assessments are summarized for participants who have achieved a confirmed PSA response.
Time Frame
Up to 1 year and 6 months
Title
Duration of PSA Response
Description
Duration of PSA response is defined as the time from the date of the earliest documented PSA response (that is subsequently confirmed) to PSA progression or death due to any cause, whichever occurs first. PSA progression is defined as a ≥ 25% increase in PSA with an absolute increase of ≥ 2 μg/L above the nadir (or above the baseline for participants with no PSA decline) after12 weeks, confirmed by a second value ≥ 3 weeks later. The nadir is defined as the lowest value at or after baseline.
Time Frame
Up to 1 year and 7 months
Title
Time to PSA Progression
Description
Time to PSA progression is defined as the time from the date of the first dose of study drug to a ≥ 25% increase in PSA with an absolute increase of ≥ 2 ng/mL above the nadir (or above the baseline for participants with no PSA decline) after 12 weeks, confirmed by a second value ≥ 3 weeks later. Death for the participants with no PSA progression is also considered as an event.
Time Frame
Up to 1 year and 7 months
Title
Time to Symptomatic Skeletal Event
Description
Time to symptomatic skeletal event (SSE) is defined as time from the date of the first dose of study drug to the first symptomatic fracture, radiation or surgery to bone, or spinal cord compression.
Time Frame
Up to 1 year and 7 months
Title
Radiographic Progression-Free Survival by IRC
Description
Radiographic progression-free survival is defined as the time from the date of the first dose of study drug to radiographic disease progression by IRC or death due to any cause, whichever occurs first.
Time Frame
Up to 1 year and 7 months
Title
Overall Survival (OS)
Description
Overall survival is defined as the time from the date of the first dose of study drug to death due to any cause.
Time Frame
Up to 1 year and 7 months
Title
Number of Participants With Treatment-Emergent Adverse Events Graded According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03
Time Frame
From the date of first Pamiparib dose until 30 days after the last dose or initiation of new anti-cancer therapy, whichever occurs first. (Up to 1 year and 7 months)
10. Eligibility
Sex
Male
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Men (≥ 18 years of age) with histologically or cytologically confirmed adenocarcinoma or poorly differentiated adenocarcinoma of the prostate without neuroendocrine differentiation with HRD deficiency by CTC-HRD assay and/or deleterious germline or somatic mutation in BRCA1 or BRCA2; mCRPC measurable disease and/or bone disease. • PSA progression with ≥ 3 rising PSA levels with ≥ 1 week between determinations and a screening PSA ≥ 2 μg/L (2 ng/mL).
Must be surgically or medically castrated with serum testosterone levels of ≤1.73 nmol/L (50 ng/dL), must have received ≥ 1 prior androgen receptor-targeted therapy, and must have received ≥ 1 taxane-based therapy.
mCRPC with 1 or 2 of the following:
Measurable disease per RECIST v1.1
Bone disease
CTC-HRD+ or BRCA1/2 mutation
PSA progression (PCWG3 criteria)
≥1 androgen receptor-targeted therapy (eg, abiraterone acetate/prednisone or enzalutamide) for mCRPC with progressive disease
≥1 taxane for metastatic prostate cancer
Key Exclusion Criteria:
Chemotherapy, hormonal therapy, biologic therapy, radionuclide therapy, immunotherapy, investigational agent, anticancer Chinese medicine, or herbal remedies ≤ 5 half-lives if the half-life is known, ≤ 14 days if not known, before start of study treatment
Continued treatment with a bisphosphonate or denosumab is allowed, if administered at a stable dose > 28 days before start of study treatment
Radiotherapy ≤ 21 days (≤ 14 days, if single fraction of radiotherapy) before start of study treatment
Prior treatment for prostate cancer with any of the following:
poly ADP ribose polymerase (PARP) inhibitor
Platinum
Cyclophosphamide
Mitoxantrone
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Guy's and St Thomas' NHS Foundation Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Cancer and Blood Center
City
Athens
State/Province
Georgia
ZIP/Postal Code
30607
Country
United States
Facility Name
Montefiore Einstein Cancer Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
Facility Name
Gosford Hospital
City
Gosford
State/Province
New South Wales
ZIP/Postal Code
2250
Country
Australia
Facility Name
Liverpool Hospital
City
Liverpool
State/Province
New South Wales
ZIP/Postal Code
2170
Country
Australia
Facility Name
Calvary Mater Newcastle
City
Waratah
State/Province
New South Wales
ZIP/Postal Code
2298
Country
Australia
Facility Name
Icon Cancer Care Foundation
City
South Brisbane
State/Province
Queensland
ZIP/Postal Code
044101
Country
Australia
Facility Name
Pan American Oncology Trials, LLC
City
Rio Piedras
ZIP/Postal Code
935
Country
Puerto Rico
Facility Name
L Hospitalet de Llobregat
City
Barcelona
ZIP/Postal Code
8035
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
Yes
Learn more about this trial
Treatment of Metastatic Castration-Resistant Prostate Cancer With Homologous Recombination Deficiency
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