Testing the Addition of Immunotherapy With Hu5F9-G4 (Magrolimab) to the Usual PARP Inhibitor, Olaparib for Treatment of Metastatic or Recurrent Breast or Castrate-Resistant Prostate Cancer With BRCA Mutations
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ClinicalTrials.gov Identifier: NCT05807126 |
Recruitment Status :
Withdrawn
(No subjects enrolled in the study)
First Posted : April 11, 2023
Last Update Posted : May 2, 2024
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Tracking Information | |||||||
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First Submitted Date ICMJE | April 8, 2023 | ||||||
First Posted Date ICMJE | April 11, 2023 | ||||||
Last Update Posted Date | May 2, 2024 | ||||||
Estimated Study Start Date ICMJE | March 5, 2024 | ||||||
Estimated Primary Completion Date | December 6, 2026 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE |
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Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||
Current Other Pre-specified Outcome Measures |
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Original Other Pre-specified Outcome Measures |
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Descriptive Information | |||||||
Brief Title ICMJE | Testing the Addition of Immunotherapy With Hu5F9-G4 (Magrolimab) to the Usual PARP Inhibitor, Olaparib for Treatment of Metastatic or Recurrent Breast or Castrate-Resistant Prostate Cancer With BRCA Mutations | ||||||
Official Title ICMJE | A Phase I/Ib Study of Anti-CD47 Hu5F9-G4 (Magrolimab) in Combination With Olaparib in Patients With BRCA1/2-Mutant Tumors | ||||||
Brief Summary | This phase I/Ib trial studies the side effects and best dose of Hu5F9-G4 (magrolimab) when given in combination with olaparib for the treatment of patients with breast or castrate-resistant prostate cancer that have spread from where they first started (primary site) to other places in the body (metastatic) or have come back after a period of improvement (recurrent) and have mutations in the BRCA1/2 genes. Magrolimab is a monoclonal antibody with potential anticancer activity and the cability to stimulate the immune system and may interfere with the ability of tumor cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Olaparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep tumor cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Combination therapy with magrolimab and olaparib may be safe and effective in treating BRCA-mutated metastatic or recurrent breast or castrate-resistant prostate cancer. | ||||||
Detailed Description | PRIMARY OBJECTIVES: I. To evaluate the safety, tolerability, toxicity profile (dose-limiting toxicities [DLTs], maximum tolerated doses [MTDs]), and phase 2 recommended dose (P2RD) of Hu5F9-G4 (magrolimab) combined with olaparib. II. To evaluate the alteration in the immune microenvironment after combination therapy including alteration of specific immune signatures and pathways related to innate immune response and STING pathway. (Dose expansion) SECONDARY OBJECTIVES: I. To evaluate the status of homologous recombination repair (HR)/DNA damage response (DDR) and other genomic mutations. II. To characterize the pharmacokinetic (PK) profile of olaparib and magrolimab in combination. EXPLORATORY OBJECTIVES: I. To explore the activity of the combination regimen in entire cohort and in the dose expansion cohorts in term of objective response rate (ORR), and progression-free survival (PFS). II. To evaluate the peripheral immune profile. III. To evaluate alterations in the HR/DDR pathway by circulating tumor (ct)DNA. IV. To correlate drug exposure with response and/or toxicity. OUTLINE: This is a dose-escalation study of magrolimab in combination with fixed-dose Olaparib followed by a dose-expansion study. Patients receive magrolimab intravenously (IV) on days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of subsequent cycles. Patients also receive olaparib orally (PO) twice a day (BID) during each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and computed tomography (CT) and/or magnetic resonance imaging (MRI) throughout the trial. Patients in the dose-expansion portion of the study also undergo tumor biopsies during screening and on study. Patients are followed for 30 days after removal from study treatment, and then followed every 12 months for 36 months or until death whichever comes first. |
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Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 1 | ||||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE | Experimental: Treatment (magrolimab, olaparib)
Patients receive magrolimab IV on days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of subsequent cycles. Patients also receive olaparib PO BID during each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT and/or MRI throughout the trial. Patients in the dose-expansion portion of the study also undergo tumor biopsies during screening and on study.
Interventions:
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Withdrawn | ||||||
Actual Enrollment ICMJE |
0 | ||||||
Original Estimated Enrollment ICMJE |
33 | ||||||
Estimated Study Completion Date ICMJE | December 6, 2026 | ||||||
Estimated Primary Completion Date | December 6, 2026 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
Listed Location Countries ICMJE | United States | ||||||
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Administrative Information | |||||||
NCT Number ICMJE | NCT05807126 | ||||||
Other Study ID Numbers ICMJE | NCI-2023-02710 NCI-2023-02710 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 10551 ( Other Identifier: University of Pittsburgh Cancer Institute LAO ) 10551 ( Other Identifier: CTEP ) UM1CA186690 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | No | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | National Cancer Institute (NCI) | ||||||
Original Responsible Party | Same as current | ||||||
Current Study Sponsor ICMJE | National Cancer Institute (NCI) | ||||||
Original Study Sponsor ICMJE | Same as current | ||||||
Collaborators ICMJE | Not Provided | ||||||
Investigators ICMJE |
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PRS Account | National Cancer Institute (NCI) | ||||||
Verification Date | April 2024 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |