Treatment of Metastatic Castration-Resistant Prostate Cancer With Homologous Recombination Deficiency

• ClinicalTrials.gov Identifier: NCT03712930
• Recruitment Status: Terminated
• First Posted: October 19, 2018
• Last Update Posted: September 23, 2020
• Sponsor: BeiGene
• Information provided by (Responsible Party): BeiGene

Tracking Information

• First Submitted Date: October 11, 2018
• First Posted Date: October 19, 2018
• Last Update Posted Date: September 23, 2020
• Actual Study Start Date: February 14, 2019
• Actual Primary Completion Date: August 6, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 1, 2020)

• Objective Response Rate determined by independent central review [ Time Frame: Up to study completion, an average of 1 year ]
• Prostate-Specific Antigen (PSA) response rate [ Time Frame: Up to study completion, an average of 1 year ]

Original Primary Outcome Measures (submitted: October 17, 2018)

• Objective Response Rate determined by independent central review [ Time Frame: through study completion, an average of 1 year ]
• Prostate-Specific Antigen (PSA) response rate [ Time Frame: through study completion, an average of 1 year ]

Current Secondary Outcome Measures (submitted: July 1, 2020)

• Duration of response [ Time Frame: Up to study completion, an average of 1 year ]
• Objective Response Rate by Investigator [ Time Frame: Up to study completion, an average of 1 year ]
• Time to Objective Response [ Time Frame: Up to study completion, an average of 1 year ]
• Clinical benefit rate [ Time Frame: Up to study completion, an average of 1 year ]
  Proportion of participants with a documented confirmed complete response (CR), partial response (PR), or stable disease

Original Secondary Outcome Measures (submitted: October 17, 2018)

• Duration of response [ Time Frame: through study completion, an average of 1 year ]
• Objective Response Rate by Investigator [ Time Frame: through study completion, an average of 1 year ]
• Time to Objective Response [ Time Frame: through study completion, an average of 1 year ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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)
• 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 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, or as clinically indicated. Administration of pamiparib will continue until disease progression, unacceptable toxicity, death or another discontinuation criterion is met.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Metastatic Castration-Resistant Prostate Cancer (mCRPC)
• HRD

Intervention

Drug: Pamiparib

60 mg orally twice daily (BID)

Other Name: BGB-290

Study Arms

Experimental: Pamiparib

Participants will receive pamiparib for a period up to 1 year

Intervention: Drug: Pamiparib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: July 1, 2020): 13
• Original Estimated Enrollment (submitted: October 17, 2018): 100
• Actual Study Completion Date: August 6, 2020
• Actual Primary Completion Date: August 6, 2020 (Final data collection date for primary outcome measure)

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
• Prior sipuleucel-T and checkpoint inhibitors"

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.

Sex/Gender

• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Puerto Rico, Spain, United States

Administrative Information

• NCT Number: NCT03712930
• Other Study ID Numbers: BGB-290-202; 2018-002587-28 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

• Responsible Party: BeiGene
• Study Sponsor: BeiGene
• Collaborators: Not Provided

Investigators

• Principal Investigator: Simon Chowdhury, MD; Guy's and St Thomas' NHS Foundation Trust

• PRS Account: BeiGene
• Verification Date: September 2020