ATM Gene MutationPhase 2NCT04030559
Niraparib Before Surgery in Treating Patients With High Risk Localized Prostate Cancer and DNA Damage Response Defects
A Phase 2 study testing Niraparib, Niraparib Tosylate Monohydrate and Radical Prostatectomy in people with ATM Gene Mutation and BRCA1 Gene Mutation, run by University of California, Davis at 1 site in United States.
Trial summary
This phase II trial studies how well niraparib, when given before surgery, works in treating patients with high risk prostate cancer that has not spread to other parts of the body (localized) and alterations in deoxyribonucleic acid (DNA) repair pathways. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- ATM Gene Mutation, BRCA1 Gene Mutation, BRCA2 Gene Mutation
- What is being tested?
- Niraparib, Niraparib Tosylate Monohydrate and Radical Prostatectomy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Feb 2020to 7 Nov 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to understand and willingness to sign an informed consent form
- Ability to adhere to the study visit schedule and other protocol requirements
- Patients must have histologically or cytologically confirmed prostate cancer that is clinically localized as defined by negative cross-section imaging and/or bone scan, and classified as high or very high risk per National Comprehensive Cancer Network (NCCN) guideline
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1
- Life expectancy >= 10 years
- Men who have selected radical prostatectomy as the primary treatment for their prostate cancer
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- Prostate cancer tumors with alterations in key DNA repair genes. This will include at least one alteration in a gene involved in DNA repair primarily through the homologous recombination pathway including BRCA1/2, ATM, CHEK1/2 FANCA, FANCD2, FANCL, GEN1, NBN, PALB2, RAD51, RAD51c, and BRIP1. Mutations will be selected that are known or likely pathogenic. Mean allele frequencies will be assessed to estimate mono versus biallelic loss of function. Patients with biallelic deletions or mutations will be prioritized for inclusion to make up at least 30% of the enrollment (i.e., 10 patients) to gauge response in this group over monoallelic loss. Final inclusion will be determined by the principal investigator
- Must be able to swallow whole capsules
- To avoid risk of drug exposure through the ejaculate, male subjects (even if they have undergone a successful vasectomy) must agree while on study therapy (including during dose interruptions) and for 3 months following the last dose of study drug to:
- Use a condom during sexual activity or practice complete sexual abstinence
- Not donate sperm
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (obtained =< 14 days of the first study treatment)
- Platelet count >= 100 x 10^9/L (obtained =< 14 days of the first study treatment)
- Hemoglobin >= 9 g/dL (may have been transfused) (obtained =< 14 days of the first study treatment)
- Total bilirubin level =< 1.5 x the upper limit of normal (ULN) range (obtained =< 14 days of the first study treatment)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels =< 2.5 x ULN or AST and ALT levels =< 5 x ULN (for subjects with documented metastatic disease to the liver) (obtained =< 14 days of the first study treatment)
- International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN (for patients on anticoagulation they must be receiving a stable dose for at least 1 week prior to randomization) (obtained =< 14 days of the first study treatment)
- Creatinine clearance > 30 mL/min by Cockcroft-Gault formula (or local institutional standard method) (obtained =< 14 days of the first study treatment)
Who cannot join
- Any condition that would prohibit the understanding or rendering of informed consent
- Prior treatment for prostate cancer
- Prior treatment with a PARP inhibitor
- Prior treatment with androgen deprivation therapy (luteinizing hormone-releasing hormone [LHRH] agonist/antagonist), antiandrogen (e.g., bicalutamide, nilutamide, enzalutamide, apalutamide), or androgen synthesis inhibitor (e.g., abiraterone, orteronel)
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
- Uncontrolled concomitant disease that in the opinion of the investigator would interfere with the patient's safety or compliance on trial
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- Severe infection that in the opinion of the investigator would interfere with the patient's safety or compliance on trial within 4 weeks prior to enrollment
- Known allergies, hypersensitivity, or intolerance to niraparib or its excipients (refer to investigator's brochure)
- Known disorder affecting gastrointestinal absorption
- Corrected QT interval by the Fridericia correction formula (QTcF) on the screening electrocardiography (ECG) > 450 msec
- Receiving concomitant medications that prolong QTc and are unable to discontinue use while receiving study drug
- History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes)
- Known human immunodeficiency virus (HIV) positive subjects with 1 or more of the following:
- Not receiving antiretroviral therapy
- A change in antiretroviral therapy within 6 months of the start of screening (except if, after consultation with the sponsor, a change is made to avoid a potential drug-drug interaction with the study drug)
- Receiving antiretroviral therapy that may interfere with the study drug (consult the principal investigator [PI] for review of medication prior to enrollment)
- CD4 count < 350 at screening
- An acquired immunodeficiency syndrome-defining opportunistic infection within 6 months of the start of screening
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
About this study
Official title: Phase II Trial of PARP Inhibitor Niraparib for Men With High Risk Prostate Cancer and DNA Damage Response Defects
This phase II trial studies how well niraparib, when given before surgery, works in treating patients with high risk prostate cancer that has not spread to other parts of the body (localized) and alterations in deoxyribonucleic acid (DNA) repair pathways. Niraparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- To assess the impact of neoadjuvant niraparib tosylate monohydrate (niraparib) therapy prior to radical prostatectomy (RP) on pathologic tumor stage, frequency of lymph node metastases and positive margin rates for patients undergoing radical prostatectomy for high-risk, clinically localized prostate cancer with alterations in DNA repair pathways.
SECONDARY OBJECTIVE:
- To assess 5-year biochemical recurrence in subjects with high-risk prostate cancer and DNA-damage response defects after prostatectomy.
OUTLINE:
Patients receive niraparib orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Following completion of treatment, patients then undergo standard of care surgery.
After completion of study treatment, patients are followed up at 30 days, every 3 months for 2 years, and then every 6 months for up to 3 years.
- Conditions
- ATM Gene Mutation, BRCA1 Gene Mutation, BRCA2 Gene Mutation, BRIP1 Gene Mutation, CDK12 Gene Mutation, CHEK1 Gene Mutation
- Being tested
- Niraparib, Niraparib Tosylate Monohydrate, Radical Prostatectomy
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NiraparibDrug
Also called MK-4827, MK4827
Given PO
Niraparib Tosylate MonohydrateDrug
Also called Zejula
Given PO
Radical ProstatectomyProcedure or surgery
Also called Prostatovesiculectomy
Undergo standard of care surgery
| Study group | Role | What they receive |
|---|---|---|
| Treatment (niraparib) | Experimental | Patients receive niraparib PO QD on days 1-28. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Following completion of treatment, patients then undergo standard of care surgery. Receives: Drug: Niraparib; Drug: Niraparib Tosylate Monohydrate; Procedure: Radical Prostatectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic Response Rate (pRR)
Number of participants who achieve complete pathologic response defined as no tumor identified on hematoxylin and eosin (H\&E) stained sections in participants who receive neoadjuvant niraparib therapy prior to radical prostatectomy (RP).
Measured: Up to the time of radical prostatectomy procedure, about 5 months from start of treatment.
Secondary outcomes (1)
Biochemical Prostate Specific Antigen (PSA) Progression Free Survival
Number of participants who achieve biochemical (PSA) progression free survival (bPFS).
Measured: Up to about 5 years from start of treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2019
- Study start25 Feb 2020
- Primary completion10 Jan 2024
- Study completion7 Nov 2025
Why it stopped: PI choice; poor accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ATM Gene MutationStudies 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
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Janssen, LP
- Responsible party
- Principal investigator, Marc Dall'Era, MD, University of California, Davis
- Investigators
- Marc Dall'Era, Principal investigator, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04030559
- Sponsor's protocol ID
- 1412676
- Other IDs
- NCI-2019-04365, UCDCC#279, P30CA093373
- Status last verified
- May 2026
- First submitted
- 22 Jul 2019
- Last updated
- 14 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Montgomery B, Mostaghel EA. Neoadjuvant Therapy Prior to Prostatectomy: Is the Glass Half Full? Eur Urol. 2023 Jun;83(6):519-520. doi: 10.1016/j.eururo.2023.01.021. Epub 2023 Jan 27. No abstract available.
PubMed 36710203
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of PARP Inhibitor Niraparib for Men With High Risk Prostate Cancer and DNA Damage Response Defects
- ClinicalTrials.gov ID
- NCT04030559
- Acronym / sponsor ID
- 1412676
- Conditions
- ATM Gene Mutation, BRCA1 Gene Mutation, BRCA2 Gene Mutation, BRIP1 Gene Mutation, CDK12 Gene Mutation, CHEK1 Gene Mutation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI choice; poor accrual
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Janssen, LP
- Study start
- 25 Feb 2020 (actual)
- Primary completion
- 10 Jan 2024 (actual)
- Study completion
- 7 Nov 2025 (actual)
- First posted
- 24 Jul 2019 (actual)
- Results
- Posted 14 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well niraparib, when given before surgery, works in treating patients with high risk prostate cancer that has not spread to other parts of the body (localized) and alterations in deoxyribonucleic acid (DNA) repair pathways. Niraparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES:
- To assess the impact of neoadjuvant niraparib tosylate monohydrate (niraparib) therapy prior to radical prostatectomy (RP) on pathologic tumor stage, frequency of lymph node metastases and positive margin rates for patients undergoing radical prostatectomy for high-risk, clinically localized prostate cancer with alterations in DNA repair pathways.
SECONDARY OBJECTIVE:
- To assess 5-year biochemical recurrence in subjects with high-risk prostate cancer and DNA-damage response defects after prostatectomy.
OUTLINE:
Patients receive niraparib orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Following completion of treatment, patients then undergo standard of care surgery.
After completion of study treatment, patients are followed up at 30 days, every 3 months for 2 years, and then every 6 months for up to 3 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (niraparib) | Experimental | Drug: Niraparib, Drug: Niraparib Tosylate Monohydrate, Procedure: Radical ProstatectomyPatients receive niraparib PO QD on days 1-28. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Following completion of treatment, patients then undergo standard of care surgery. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Ability to understand and willingness to sign an informed consent form
- Ability to adhere to the study visit schedule and other protocol requirements
- Patients must have histologically or cytologically confirmed prostate cancer that is clinically localized as defined by negative cross-section imaging and/or bone scan, and classified as high or very high risk per National Comprehensive Cancer Network (NCCN) guideline
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1
- Life expectancy >= 10 years
Key exclusion criteria (18 listed)
- Any condition that would prohibit the understanding or rendering of informed consent
- Prior treatment for prostate cancer
- Prior treatment with a PARP inhibitor
- Prior treatment with androgen deprivation therapy (luteinizing hormone-releasing hormone [LHRH] agonist/antagonist), antiandrogen (e.g., bicalutamide, nilutamide, enzalutamide, apalutamide), or androgen synthesis inhibitor (e.g., abiraterone, orteronel)
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
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 |
|---|---|---|
| NiraparibAlso: MK-4827, MK4827Given PO | Drug | Treatment (niraparib) |
| Niraparib Tosylate MonohydrateAlso: ZejulaGiven PO | Drug | Treatment (niraparib) |
| Radical ProstatectomyAlso: ProstatovesiculectomyUndergo standard of care surgery | Procedure or surgery | Treatment (niraparib) |
Primary outcome
Pathologic Response Rate (pRR)
Time frame: Up to the time of radical prostatectomy procedure, about 5 months from start of treatment.
Number of participants who achieve complete pathologic response defined as no tumor identified on hematoxylin and eosin (H\&E) stained sections in participants who receive neoadjuvant niraparib therapy prior to radical prostatectomy (RP).
1 secondary outcome
Biochemical Prostate Specific Antigen (PSA) Progression Free Survival
Time frame: Up to about 5 years from start of treatment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36710203Montgomery B, Mostaghel EA. Neoadjuvant Therapy Prior to Prostatectomy: Is the Glass Half Full? Eur Urol. 2023 Jun;83(6):519-520. doi: 10.1016/j.eururo.2023.01.021. Epub 2023 Jan 27. No abstract available.
- Learn more or sign up for the study here!Link provided by the sponsor.
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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.
Marc Dall'Era principal investigator
University of California, Davis
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, Niraparib Tosylate Monohydrate and Radical Prostatectomy in people with ATM Gene Mutation and BRCA1 Gene Mutation, run by University of California, Davis 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 18 inclusion and 18 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: stopped early, as of the sponsor's last update on 14 May 2026. 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?
Yes. Results are posted in the registry (first posted 14 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathologic Response Rate (pRR) (time frame: Up to the time of radical prostatectomy procedure, about 5 months from start of treatment.). 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 NCT04030559, 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 14 May 2026.