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Trial record 4 of 4 for:    MEL-01

Efficacy and Safety Study of Niraparib in Melanoma With Genetic Homologous Recombination (HR) Mutation

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ClinicalTrials.gov Identifier: NCT03925350
Recruitment Status : Recruiting
First Posted : April 24, 2019
Last Update Posted : April 24, 2019
Sponsor:
Collaborators:
Mt. Sinai Medical Center, Miami
Tesaro, Inc.
Information provided by (Responsible Party):
Kevin Kim, California Pacific Medical Center Research Institute

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 and/or BRAF-targeting therapy.

Condition or disease Intervention/treatment Phase
Metastatic Melanoma Drug: Niraparib Phase 2

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 30.5% 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 mutation/alteration 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 41 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Niraparib in Patients With Advanced Melanoma With Genetic Homologous Recombination (HR) Mutation / Alteration
Actual Study Start Date : March 20, 2019
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : February 2023


Arm Intervention/treatment
Experimental: Niraparib
Patients receive niraparib PO daily
Drug: Niraparib
300 mg PO daily




Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: 6 months ]
    ORR of niraparib in patients with advanced melanoma with genetic homologous recombination (HR) mutation/ alteration using RECIST v1.1


Secondary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: 2 years ]
    PFS of patients with advanced melanoma with genetic HR mutation/ alteration who are treated with niraparib

  2. overall survival (OS) [ Time Frame: 2 years ]
    OS of patients with advanced melanoma with genetic HR mutation/ alteration who are treated with niraparib

  3. Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 2 years ]
    Evaluation of the safety profile of niraparib treatment in patients with advanced melanoma with genetic homologous recombination (HR) mutation/ alteration



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have genetic homologous recombination (HR) mutation/ alteration including ARID1A/B, ARID2, ATM, ATR, BARD1, BRCA1/2, BAP1, BRIP1, CHEK2, FANCD2, MRN11A, RAD50, RAD51, RAD54B
  • Disease must have progressed on the standard systemic therapies or they could not have tolerated the standard therapies.
  • ECOG PS >/=1
  • Have measurable metastatic disease according to RECIST 1.1
  • Prior systemic cytotoxic therapy up to 1 regimens is allowed; There is no limit on the number of prior immunotherapy or targeted therapy regimens.
  • All adverse events associated with prior treatment must have resolved to ≤ Grade 1 prior to day 1 of the study drug administration.

Exclusion Criteria:

  • Previously treated with a PARP inhibitor
  • Symptomatic brain metastasis or active brain lesions ≥6 mm size or those
  • Require steroid treatment for brain lesions or leptomeningeal disease
  • Systemic cancer therapy within 14 days prior to day 1 of the study drug administration
  • Any major surgery ≤ 3 weeks of starting the study and patient must have recovered from any effects of any major surgery
  • Investigational therapy administered ≤ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational
  • Prior radiotherapy encompassing > 20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy
  • Medical history of immunocompromised condition
  • Systemic treatment of another type of cancer ≤ 2 years prior to registration
  • Known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)

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): NCT03925350


Contacts
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Contact: Peter Gasper 415-600-3472 gasperjp@sutterhealth.org

Locations
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United States, California
California Pacific Medical Center Research Institute Recruiting
San Francisco, California, United States, 94115
Contact: Peter Gasper    415-600-3472    peter@cpmcri.org   
Sponsors and Collaborators
California Pacific Medical Center Research Institute
Mt. Sinai Medical Center, Miami
Tesaro, Inc.
Investigators
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Principal Investigator: Kevin Kim, MD California Pacific Medical Center

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Responsible Party: Kevin Kim, Principal Investigator, California Pacific Medical Center Research Institute
ClinicalTrials.gov Identifier: NCT03925350     History of Changes
Other Study ID Numbers: CPMC17-MEL01
First Posted: April 24, 2019    Key Record Dates
Last Update Posted: April 24, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Kevin Kim, California Pacific Medical Center Research Institute:
Homologous recombination (HR)
Mutation
Niraparib
PARP inhibitor

Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Niraparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents