Metastatic MelanomaPhase 2NCT03925350
Efficacy and Safety Study of Niraparib in Melanoma With Genetic Homologous Recombination (HR) Mutation
A Phase 2 study testing Niraparib in people with Metastatic Melanoma, run by California Pacific Medical Center Research Institute at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma
- What is being tested?
- Niraparib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Mar 2019to Feb 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have genetic homologous recombination (HR) mutation/ alteration including ARID1A/B, ARID2, ATM, ATR, ATRX, BARD1, BRCA1/2, BAP1, BRIP1, CHEK2, FANCD2, MRN11A, PALB2, 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.
Who cannot join
- 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
Show all 10Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
California Pacific Medical Center Research Institute
San Francisco, California, 94115
Emilia Janiczek, 415-600-1544, janicze@sutterhealth.org
About this study
Official title: A Phase II Study of Niraparib in Patients With Advanced Melanoma With Genetic Homologous Recombination (HR) Mutation / Alteration
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.
Read the 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.
- Conditions
- Metastatic Melanoma
- Being tested
- Niraparib
- Keywords
- Homologous recombination (HR), Mutation, Niraparib, PARP inhibitor
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NiraparibDrug
300 mg PO daily
| Study group | Role | What they receive |
|---|---|---|
| Niraparib | Experimental | Patients receive niraparib PO daily Receives: Drug: Niraparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
ORR of niraparib in patients with advanced melanoma with genetic homologous recombination (HR) mutation/ alteration using RECIST v1.1
Measured: 6 months
Secondary outcomes (3)
Progression-free survival (PFS)
PFS of patients with advanced melanoma with genetic HR mutation/ alteration who are treated with niraparib
Measured: 2 years
overall survival (OS)
OS of patients with advanced melanoma with genetic HR mutation/ alteration who are treated with niraparib
Measured: 2 years
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Evaluation of the safety profile of niraparib treatment in patients with advanced melanoma with genetic homologous recombination (HR) mutation/ alteration
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2019
- Study start20 Mar 2019
- Primary completionFeb 2022 (estimated)
- Study completionFeb 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (estimated)
Sponsor and investigators
- Lead sponsor
- California Pacific Medical Center Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Tesaro, Inc., Vanderbilt-Ingram Cancer Center, Huntsman Cancer Institute
- Responsible party
- Principal investigator, Kevin Kim, California Pacific Medical Center Research Institute
- Investigators
- Kevin Kim, MD, Principal investigator, California Pacific Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03925350
- Sponsor's protocol ID
- CPMC17-MEL01
- Status last verified
- Oct 2021
- First submitted
- 15 Mar 2019
- Last updated
- 22 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Kim KB, Desprez PY, de Semir D, Woo RWL, Sharma A, Jones R, Caressi C, Nosrati M, Janiczek E, Rivera Penafiel J, Kashani-Sabet M. Phase II Study of Niraparib in Patients With Advanced Melanoma With Homologous Recombination Pathway Gene Mutations. JCO Precis Oncol. 2025 May;9:e2400658. doi: 10.1200/PO-24-00658. Epub 2025 May 15.
PubMed 40373259
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Niraparib in Patients With Advanced Melanoma With Genetic Homologous Recombination (HR) Mutation / Alteration
- ClinicalTrials.gov ID
- NCT03925350
- Acronym / sponsor ID
- CPMC17-MEL01
- Conditions
- Metastatic Melanoma
- Keywords
- Homologous recombination (HR), Mutation, Niraparib, PARP inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 41 participants (estimated)
- Lead sponsor
- California Pacific Medical Center Research InstituteUniversity, hospital or other
- Collaborators
- Tesaro, Inc., Vanderbilt-Ingram Cancer Center, Huntsman Cancer Institute
- Study start
- 20 Mar 2019 (actual)
- Primary completion
- Feb 2022 (estimated)
- Study completion
- Feb 2023 (estimated)
- First posted
- 24 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Niraparib | Experimental | Drug: NiraparibPatients receive niraparib PO daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Have genetic homologous recombination (HR) mutation/ alteration including ARID1A/B, ARID2, ATM, ATR, ATRX, BARD1, BRCA1/2, BAP1, BRIP1, CHEK2, FANCD2, MRN11A, PALB2, 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.
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Niraparib300 mg PO daily | Drug | Niraparib |
Primary outcome
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
3 secondary outcomes
Progression-free survival (PFS)
Time frame: 2 years
overall survival (OS)
Time frame: 2 years
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2021.
- Derived from this study: PubMed 40373259Kim KB, Desprez PY, de Semir D, Woo RWL, Sharma A, Jones R, Caressi C, Nosrati M, Janiczek E, Rivera Penafiel J, Kashani-Sabet M. Phase II Study of Niraparib in Patients With Advanced Melanoma With Homologous Recombination Pathway Gene Mutations. JCO Precis Oncol. 2025 May;9:e2400658. doi: 10.1200/PO-24-00658. Epub 2025 May 15.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kevin Kim, MD principal investigator
California Pacific Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Niraparib in people with Metastatic Melanoma, run by California Pacific Medical Center Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Emilia Janiczek (415-600-1544, janicze@sutterhealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03925350, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2021.