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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03712930
Recruitment Status : Terminated (Sponsor's decision to revisit the development approach for prostate cancer.)
First Posted : October 19, 2018
Results First Posted : November 17, 2021
Last Update Posted : November 17, 2021
Sponsor:
Information provided by (Responsible Party):
BeiGene

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

Condition or disease Intervention/treatment Phase
Metastatic Castration-Resistant Prostate Cancer (mCRPC) Homologous Recombination Deficiency (HRD) Drug: Pamiparib Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : February 5, 2019
Actual Primary Completion Date : August 6, 2020
Actual Study Completion Date : September 2, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Pamiparib
Participants will receive pamiparib for a period up to 1 year
Drug: Pamiparib
60 mg orally twice daily (BID)
Other Name: BGB-290




Primary Outcome Measures :
  1. Objective Response Rate (ORR) Determined by Independent Review Committee [ Time Frame: Up to 1 year and 6 months ]
    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).

  2. Prostate-Specific Antigen (PSA) Response Rate [ Time Frame: Up to 1 year and 6 months ]
    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 :
  1. Duration of Response (DOR) by IRC [ Time Frame: Up to 1 year and 7 months ]
    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.

  2. Objective Response Rate by Investigator [ Time Frame: Up to 1 year and 6 months ]
    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.

  3. Time to Objective Response by Investigator [ Time Frame: Up to 1 year and 6 months ]
    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.

  4. Clinical Benefit Rate By Investigator [ Time Frame: Up to 1 year and 6 months ]
    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.

  5. Time to PSA Response [ Time Frame: Up to 1 year and 6 months ]
    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.

  6. Duration of PSA Response [ Time Frame: Up to 1 year and 7 months ]
    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.

  7. Time to PSA Progression [ Time Frame: Up to 1 year and 7 months ]
    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.

  8. Time to Symptomatic Skeletal Event [ Time Frame: Up to 1 year and 7 months ]
    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.

  9. Radiographic Progression-Free Survival by IRC [ Time Frame: Up to 1 year and 7 months ]
    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.

  10. Overall Survival (OS) [ Time Frame: Up to 1 year and 7 months ]
    Overall survival is defined as the time from the date of the first dose of study drug to death due to any cause.

  11. 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) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03712930


Locations
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United States, Georgia
University Cancer and Blood Center
Athens, Georgia, United States, 30607
United States, New York
Montefiore Einstein Cancer Center
Bronx, New York, United States, 10461
United States, Washington
University of Washington
Seattle, Washington, United States, 98195
Australia, New South Wales
Gosford Hospital
Gosford, New South Wales, Australia, 2250
Liverpool Hospital
Liverpool, New South Wales, Australia, 2170
Calvary Mater Newcastle
Waratah, New South Wales, Australia, 2298
Australia, Queensland
Icon Cancer Care Foundation
South Brisbane, Queensland, Australia, 044101
Puerto Rico
Pan American Oncology Trials, LLC
Rio Piedras, Puerto Rico, 935
Spain
L Hospitalet de Llobregat
Barcelona, Spain, 8035
Sponsors and Collaborators
BeiGene
Investigators
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Principal Investigator: Study Director Guy's and St Thomas' NHS Foundation Trust
  Study Documents (Full-Text)

Documents provided by BeiGene:
Study Protocol  [PDF] October 16, 2018
Statistical Analysis Plan  [PDF] November 2, 2020

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Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT03712930    
Other Study ID Numbers: BGB-290-202
2018-002587-28 ( EudraCT Number )
First Posted: October 19, 2018    Key Record Dates
Results First Posted: November 17, 2021
Last Update Posted: November 17, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases