Ignite Creation Date:
2025-12-25 @ 2:16 AM
Ignite Modification Date:
2025-12-26 @ 12:45 AM
Study NCT ID:
NCT04493060
Status:
COMPLETED
Last Update Posted:
2025-08-07
First Post:
2020-07-27
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Niraparib and Dostarlimab for the Treatment of Germline or Somatic BRCA1/2 and PALB2 Mutated Metastatic Pancreatic Cancer
Sponsor:
Mayo Clinic
Organization:
Study Overview
Official Title:
Phase II Study of Niraparib and TSR-042 in Patients With Germline or Somatic BRCA1/2 and PALB2-Related Pancreatic Cancer
Status:
COMPLETED
Status Verified Date:
2025-01
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 phase II trial studies how well niraparib and dostarlimab work in treating patients with germline or somatic BRCA1/2 and PALB2 mutated pancreatic cancer that has spread to other places in the body (metastatic). Niraparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as dostarlimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving niraparib and dostarlimab may kill more tumor cells.
Detailed Description:
PRIMARY OBJECTIVE:
I. To determine antitumor activity as measured by disease control rate at 12 weeks (DCR12) as assessed using immune-modified Response Evaluation Criteria in Solid Tumors (iRECIST) in select homologous recombination repair (HRR) deficient pancreatic cancer patients with HRR deficiency (defined as mutations in BRCA 1/ 2, or PALB2).
SECONDARY OBJECTIVES:
I. To assess adverse events according to the current National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) and other safety parameters.
II. To assess the time to next treatment (TTNT), objective response rate (ORR), time to and duration of response and duration of confirmed stable disease according to iRECIST.
III. To assess progression-free survival. IV. To assess overall survival.
CORRELATIVE RESEARCH OBJECTIVES:
I. To assess germline deoxyribonucleic acid (DNA) and serum markers of immune response.
II. To determine changes in circulating tumor DNA (ctDNA) profile after therapy with a PARP inhibitor (i) and a PD-1 inhibitor.
III. To study mechanisms of resistance in ctDNA profile after therapy with a PARPi and a PD-1 inhibitor.
IV. To assess the tumor microenvironment for immune related changes (immune infiltration, PD-L1 and PD-1 expression, tumor-infiltrating lymphocytes \[TIL\]).
V. To assess genetic profile of the tumor pre- and post-treatment. VI. To determine changes in the cytokine profile pre- and post-treatment.
OUTLINE:
Patients receive niraparib orally (PO) once daily (QD) on days 1-21. Patients also receive dostarlimab intravenously (IV) over 30 minutes on day 1 every 3 weeks (Q3W) for cycles 1-4 and every 6 weeks (Q6W) for subsequent cycles. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, every 3 months until progressive disease (PD), and then every 6 months for up to 5 years after registration.
I. To determine antitumor activity as measured by disease control rate at 12 weeks (DCR12) as assessed using immune-modified Response Evaluation Criteria in Solid Tumors (iRECIST) in select homologous recombination repair (HRR) deficient pancreatic cancer patients with HRR deficiency (defined as mutations in BRCA 1/ 2, or PALB2).
SECONDARY OBJECTIVES:
I. To assess adverse events according to the current National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) and other safety parameters.
II. To assess the time to next treatment (TTNT), objective response rate (ORR), time to and duration of response and duration of confirmed stable disease according to iRECIST.
III. To assess progression-free survival. IV. To assess overall survival.
CORRELATIVE RESEARCH OBJECTIVES:
I. To assess germline deoxyribonucleic acid (DNA) and serum markers of immune response.
II. To determine changes in circulating tumor DNA (ctDNA) profile after therapy with a PARP inhibitor (i) and a PD-1 inhibitor.
III. To study mechanisms of resistance in ctDNA profile after therapy with a PARPi and a PD-1 inhibitor.
IV. To assess the tumor microenvironment for immune related changes (immune infiltration, PD-L1 and PD-1 expression, tumor-infiltrating lymphocytes \[TIL\]).
V. To assess genetic profile of the tumor pre- and post-treatment. VI. To determine changes in the cytokine profile pre- and post-treatment.
OUTLINE:
Patients receive niraparib orally (PO) once daily (QD) on days 1-21. Patients also receive dostarlimab intravenously (IV) over 30 minutes on day 1 every 3 weeks (Q3W) for cycles 1-4 and every 6 weeks (Q6W) for subsequent cycles. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, every 3 months until progressive disease (PD), and then every 6 months for up to 5 years after registration.
Study Oversight
Has Oversight DMC:
True
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?: