Ignite Creation Date:
2024-05-06 @ 1:05 PM
Last Modification Date:
2024-10-26 @ 1:08 PM
Study NCT ID:
NCT03925350
Status:
UNKNOWN
Last Update Posted:
2021-10-22
First Post:
2019-03-15
Brief Title:
Efficacy and Safety Study of Niraparib in Melanoma With Genetic Homologous Recombination HR Mutation
Sponsor:
California Pacific Medical Center Research Institute
Organization:
California Pacific Medical Center Research Institute
Study Overview
Official Title:
A Phase II Study of Niraparib in Patients With Advanced Melanoma With Genetic Homologous Recombination HR Mutation Alteration
Status:
UNKNOWN
Status Verified Date:
2021-10
Last Known Status:
RECRUITING
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 open-label phase II trial studies how well niraparib works in treating patients with advanced metastatic melanoma with the homologous recombination HR pathway gene mutation alteration Niraparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth The trial is designed to assess the efficacy and safety of niraparib in patients with HR mutation alteration whose disease progressed on prior immunotherapy andor BRAF-targeting therapy
Detailed Description:
Treatment with PARP inhibitors could represent a novel opportunity to selectively kill a subset of cancer cells with deficiencies in DNA repair pathways For example a tumor arising in a patient with a germline BRCA mutation gBRCAmut has a defective homologous recombination DNA repair pathway and would be increasingly dependent on NHEJ alt-NHEJ and BER for maintenance of genomic integrity PARP inhibitors block alt-NHEJ and BER forcing tumors with BRCA deficiencies to use the error-prone NHEJ to fix double-strand breaks Non-BRCA deficiencies in homologous recombination DNA repair genes could also enhance tumor cell sensitivity to PARP inhibitors The rationale for anticancer activity in a subset of non-gBRCAmut tumors is that they share distinctive DNA repair defects with gBRCAmut carriers a phenomenon broadly described as BRCAness DNA repair defects can be caused by germline or somatic alterations to the homologous recombination DNA repair pathway Homologous recombination is a complex pathway and several genes other than BRCA1 and BRCA2 are required either to sense or repair DNA double-strand breaks via the homologous recombination pathway Therefore PARP inhibitors are also selectively cytotoxic for cancer cells with deficiencies in DNA repair proteins other than BRCA1 and BRCA2
In melanoma genetic HR mutation alterations are rather common Retrospective data showed that nearly 305 of cutaneous melanoma harbors a mutation in at least 1 of the HR genes in their tumor The most commonly altered gene was ARID2 followed by ARID1A FANCA ATM BRCA1 ATRX and BRCA2 ATR BRCA1 and BRIP1
These findings provide a strong rationale to evaluate the clinical efficacy of a PARP inhibitor in patients with advanced cancers with HR mutationalteration or HR deficiency Therefore the investigators propose a phase II study of niraparib in patients with advanced melanoma with genetic homologous recombination mutation alteration
In this clinical study clinical efficacy of niraparib will be evaluated by assessing an objective clinical response rate in patients with advanced metastatic melanoma with the homologous recombination HR pathway gene mutation alteration All participating patients will receive niraparib 300 mg a day until disease progresses or they experience intolerable toxicity
In melanoma genetic HR mutation alterations are rather common Retrospective data showed that nearly 305 of cutaneous melanoma harbors a mutation in at least 1 of the HR genes in their tumor The most commonly altered gene was ARID2 followed by ARID1A FANCA ATM BRCA1 ATRX and BRCA2 ATR BRCA1 and BRIP1
These findings provide a strong rationale to evaluate the clinical efficacy of a PARP inhibitor in patients with advanced cancers with HR mutationalteration or HR deficiency Therefore the investigators propose a phase II study of niraparib in patients with advanced melanoma with genetic homologous recombination mutation alteration
In this clinical study clinical efficacy of niraparib will be evaluated by assessing an objective clinical response rate in patients with advanced metastatic melanoma with the homologous recombination HR pathway gene mutation alteration All participating patients will receive niraparib 300 mg a day until disease progresses or they experience intolerable toxicity
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