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

Metastatic Castration-Resistant Prostate Cancer (mCRPC) Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03712930
• Other study ID #: BGB-290-202
• Secondary ID: 2018-002587-28
• Status: Terminated
• Phase: Phase 2
• Start date: February 5, 2019
• Est. completion date: September 2, 2020

Study information

• Verified date: October 2021
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. completion date: September 2, 2020
• Est. primary completion date: August 6, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Homologous Recombination Deficiency (HRD)
• Metastatic Castration-Resistant Prostate Cancer (mCRPC)
• Prostatic Neoplasms

Intervention

Drug:
• Pamiparib
60 mg orally twice daily (BID)

Locations

Country	Name	City	State
Australia	Gosford Hospital	Gosford	New South Wales
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Icon Cancer Care Foundation	South Brisbane	Queensland
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Puerto Rico	Pan American Oncology Trials, LLC	Rio Piedras
Spain	L Hospitalet de Llobregat	Barcelona
United States	University Cancer and Blood Center	Athens	Georgia
United States	Montefiore Einstein Cancer Center	Bronx	New York
United States	University of Washington	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Countries where clinical trial is conducted

United States,  Australia,  Puerto Rico,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Up to 1 year and 6 months
Primary	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.	Up to 1 year and 6 months
Secondary	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.	Up to 1 year and 7 months
Secondary	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.	Up to 1 year and 6 months
Secondary	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.	Up to 1 year and 6 months
Secondary	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.	Up to 1 year and 6 months
Secondary	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.	Up to 1 year and 6 months
Secondary	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.	Up to 1 year and 7 months
Secondary	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.	Up to 1 year and 7 months
Secondary	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.	Up to 1 year and 7 months
Secondary	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.	Up to 1 year and 7 months
Secondary	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.	Up to 1 year and 7 months
Secondary	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		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)