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
Brief Title
Treatment of Metastatic Castration-Resistant Prostate Cancer With Homologous Recombination Deficiency
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Homologous Recombination Deficiency (HRD)
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.
* 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.
Inclusion Criteria
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
Inclusion/
* 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
Inclusion/
Gender
Male
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03712930
Org Class
Industry
Org Full Name
BeiGene
Org Study Id
BGB-290-202
Overall Status
Terminated
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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)
Primary Outcomes
Outcome 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).
Outcome Measure
Objective Response Rate (ORR) Determined by Independent Review Committee
Outcome Time Frame
Up to 1 year and 6 months
Outcome 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.
Outcome Measure
Prostate-Specific Antigen (PSA) Response Rate
Outcome Time Frame
Up to 1 year and 6 months
Secondary Ids
Secondary Id
2018-002587-28
Secondary Outcomes
Outcome 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.
Outcome Time Frame
Up to 1 year and 7 months
Outcome Measure
Duration of Response (DOR) by IRC
Outcome 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.
Outcome Time Frame
Up to 1 year and 6 months
Outcome Measure
Objective Response Rate by Investigator
Outcome 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.
Outcome Time Frame
Up to 1 year and 6 months
Outcome Measure
Time to Objective Response by Investigator
Outcome 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.
Outcome Time Frame
Up to 1 year and 6 months
Outcome Measure
Clinical Benefit Rate By Investigator
Outcome 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.
Outcome Time Frame
Up to 1 year and 6 months
Outcome Measure
Time to PSA Response
Outcome 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.
Outcome Time Frame
Up to 1 year and 7 months
Outcome Measure
Duration of PSA Response
Outcome 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.
Outcome Time Frame
Up to 1 year and 7 months
Outcome Measure
Time to PSA Progression
Outcome 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.
Outcome Time Frame
Up to 1 year and 7 months
Outcome Measure
Time to Symptomatic Skeletal Event
Outcome 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.
Outcome Time Frame
Up to 1 year and 7 months
Outcome Measure
Radiographic Progression-Free Survival by IRC
Outcome Description
Overall survival is defined as the time from the date of the first dose of study drug to death due to any cause.
Outcome Time Frame
Up to 1 year and 7 months
Outcome Measure
Overall Survival (OS)
Outcome 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)
Outcome Measure
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
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Sanjay Goel
Investigator Email
sgoel@montefiore.org
Investigator Phone
718-405-8404