Ignite Creation Date:
2024-05-06 @ 7:53 PM
Last Modification Date:
2024-10-26 @ 3:16 PM
Study NCT ID:
NCT06177171
Status:
RECRUITING
Last Update Posted:
2024-05-01
First Post:
2023-12-11
Brief Title:
Olaparib and ASTX727 in BRCA12- and Homologous Recombination Deficient HRD-Mutated Tumors
Sponsor:
Pamela Munster
Organization:
University of California San Francisco
Study Overview
Official Title:
A Phase IIb Study of Olaparib and ASTX727 in BRCA12- and HRD-mutated Tumors
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a single center phase IIb clinical trial evaluating the combination of the poly adenosine diphosphate-ribose polymerase PARP inhibitor olaparib with the DNA methyltransferase DNMT inhibitor ASTX727 which is an oral formulation of decitabine with cedazuridine a cytidine deaminase inhibitor that allows for oral administration The study population consists of adults with advancedmetastatic solid tumor malignancies with germline or somatic mutations in the HRR pathway ie BReast CAncer gene 1 BRCA1 BReast CAncer gene 2BRCA2 Partner And Localizer of BRCA2 PALB2 ATM andor Checkpoint kinase 2 CHEK2 mutations
Detailed Description:
PRIMARY OBJECTIVES
I To assess the safety and tolerability of olaparib and ASTX7272 in patients with advanced solid tumors and germline or somatic mutations in the homologous recombination repair HRR pathway
II To determine the maximum tolerated dose MTD and recommended phase II dose RP2D for olaparib and ASTX7272 in patients with advanced solid tumors and germline or somatic mutations in the HRR pathway
SECONDARY OBJECTIVES
I To evaluate the preliminary efficacy of the recommended dose level of olaparib and ASTX727 in patients with solid tumor malignancies and germline or somatic mutations in the HRR pathway
EXPLORATORY OBJECTIVES
I To characterize HRD mutations in tumor samples and assess functional impact on HRR
II To assess cell free deoxyribonucleic acid cfDNA as a predictive biomarker of response and resistance
III To create patient-derived xenograft PDX and patient-derived organoid PDO models for sensitive and resistant tumors from patients treated with olaparib and ASTX727
OUTLINE
Testing for DNA repair mutations should occur prior to study consent or prior to enrollment via a Clinical Laboratory Improvement Amendments of 1988 CLIA-approved test This study uses a 33 design In phase 1 participants will be assigned to the starting dose If no DLTs are found in the first cycle for the first 3 participants an additional cohort at the next dose level will open for enrollment In phase 1b participants will receive the recommended phase 2 dose RP2D Participants will be followed for approximately 30 days after discontinuation of study treatment for safety and every 16 weeks for up to 2 years
I To assess the safety and tolerability of olaparib and ASTX7272 in patients with advanced solid tumors and germline or somatic mutations in the homologous recombination repair HRR pathway
II To determine the maximum tolerated dose MTD and recommended phase II dose RP2D for olaparib and ASTX7272 in patients with advanced solid tumors and germline or somatic mutations in the HRR pathway
SECONDARY OBJECTIVES
I To evaluate the preliminary efficacy of the recommended dose level of olaparib and ASTX727 in patients with solid tumor malignancies and germline or somatic mutations in the HRR pathway
EXPLORATORY OBJECTIVES
I To characterize HRD mutations in tumor samples and assess functional impact on HRR
II To assess cell free deoxyribonucleic acid cfDNA as a predictive biomarker of response and resistance
III To create patient-derived xenograft PDX and patient-derived organoid PDO models for sensitive and resistant tumors from patients treated with olaparib and ASTX727
OUTLINE
Testing for DNA repair mutations should occur prior to study consent or prior to enrollment via a Clinical Laboratory Improvement Amendments of 1988 CLIA-approved test This study uses a 33 design In phase 1 participants will be assigned to the starting dose If no DLTs are found in the first cycle for the first 3 participants an additional cohort at the next dose level will open for enrollment In phase 1b participants will receive the recommended phase 2 dose RP2D Participants will be followed for approximately 30 days after discontinuation of study treatment for safety and every 16 weeks for up to 2 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2023-10542 | REGISTRY | NCI Clinical Trials Reporting Program | httpsreporternihgovquickSearch5R01CA255613-02 |
| 5R01CA255613-02 | NIH | None | None |