Clinical trial NCT03712930: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Homologous Recombination Deficiency (HRD)
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2018-10-19
Enrollment: 13
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Objective Response Rate (ORR) Determined by Independent Review Committee
timeFrame: Up to 1 year and 6 months
measure: Prostate-Specific Antigen (PSA) Response Rate
timeFrame: Up to 1 year and 6 months
Secondary outcomes:
measure: Duration of Response (DOR) by IRC
timeFrame: Up to 1 year and 7 months
measure: Objective Response Rate by Investigator
timeFrame: Up to 1 year and 6 months
measure: Time to Objective Response by Investigator
timeFrame: Up to 1 year and 6 months
measure: Clinical Benefit Rate By Investigator
timeFrame: Up to 1 year and 6 months
measure: Time to PSA Response
timeFrame: Up to 1 year and 6 months
measure: Duration of PSA Response
timeFrame: Up to 1 year and 7 months
measure: Time to PSA Progression
timeFrame: Up to 1 year and 7 months
measure: Time to Symptomatic Skeletal Event
timeFrame: Up to 1 year and 7 months
measure: Radiographic Progression-Free Survival by IRC
timeFrame: Up to 1 year and 7 months
measure: Overall Survival (OS)
timeFrame: Up to 1 year and 7 months
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
timeFrame: 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)
Other outcomes:
Locations:
city: Athens
country: United States
facility: University Cancer and Blood Center
state: Georgia
city: Bronx
country: United States
facility: Montefiore Einstein Cancer Center
state: New York
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Gosford
country: Australia
facility: Gosford Hospital
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: South Brisbane
country: Australia
facility: Icon Cancer Care Foundation
state: Queensland
city: Rio Piedras
country: Puerto Rico
facility: Pan American Oncology Trials, LLC
city: Barcelona
country: Spain
facility: L Hospitalet de Llobregat
Study officials:
affiliation: Guy's and St Thomas' NHS Foundation Trust
name: Study Director
role: PRINCIPAL_INVESTIGATOR
References: