Metastatic CancerPhase 2NCT04992013
Niraparib in Tumors Metastatic to the CNS
A Phase 2 study testing Niraparib in people with Metastatic Cancer and Central Nervous System Cancer, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
This research is being done to see how effective the drug niraparib is against cancer that has metastasized to the central nervous system (CNS). This research study involves the study drug niraparib. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Cancer, Central Nervous System Cancer
- What is being tested?
- Niraparib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Apr 2022to 1 Jun 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Participants must have histologically or cytologically confirmed disease from any solid tumor.
- Patients must be asymptomatic or minimally symptomatic from CNS metastases for at least 7 days prior to initiation of study therapy. Minimal symptoms is defined as not requiring escalating doses of steroids or seizure medications for at least 7 days prior to initiation of study therapy.
- Participants must have measurable disease in the CNS, defined as at least one lesion that can be accurately measured in at least one dimension as ≥10 mm.
- Participants must have progressive CNS lesions, as defined by one of the following:
- Patients may have multiple progressive CNS lesions, some of which have been treated by SRS or surgery. Patients are eligible if they have one or more un-treated (by surgery or SRS) progressive lesions that is measurable.
- Patients have measurable residual or progressive lesions after surgery.
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- Patients who have had prior WBRT and/or SRS are eligible but there needs to be unequivocal evidence of progression of at least one lesion treated by radiation (e.g. tissue diagnosis). Biopsy can be considered for definitive diagnosis.
- Patients who have previously been treated with systemic therapy for CNS metastases are eligible.
- Diagnosis of triple negative breast cancer or ovarian cancer, or any cancer histology with the presence of alteration in BRCA1, BRCA2, PARP metabolism, DNA repair pathways and HRD (homologous recombination deficiency) genes in the metastatic site as described in Section 9.2 using a CLIA-certified assay. Specific genetic changes in the HRD signature or DNA repair pathway include mutations in ATM, BAP1, BARD1, BRCA1, BRCA2, BRIP1, MRE11A, NBN, PALB2, RAD50, RAD51B, RAD51C, RAD51D, RAD54B, RAD54L, ATR, XRCC2, and XRCC3.
- Age > 18 years. The toxicity of niraparib in children is unknown.
- ECOG performance status ≤ 2 (Karnofsky ≥ 60, see Appendix A).
- Participants must have normal organ and marrow function as defined below:
- leukocytes ≥3,000/mcL
- absolute neutrophil count ≥1,500/mcL
- platelets ≥100,000/mcL
- hemoglobin ≥9g/dL
- total bilirubin total bilirubin < 1.5 x institutional upper limit of normal OR > 1.5 x institutional upper limit of normal allowed if direct bilirubin is within normal range. Patients with Gilberts will be eligible if total bili < 3.
- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
- creatinine clearance ≥30 mL/min/1.73 m2 using the Cockcrof-Gault equation.
- baseline QTc <480ms
- Female participant has a negative urine or serum pregnancy test within 72 hours prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 180 days after the last dose of study treatment, or is of nonchildbearing potential. Nonchildbearing potential is defined as follows (by other than medical reasons):
- ≥45 years of age and has not had menses for >1 year
- Patients who have been amenorrhoeic for <2 years without history of a hysterectomy and oo phorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation
- Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use a highly effective barrier methods throughout the study, starting with the screening visit through 180 days after the last dose of study treatment. See Section 4.4 for a list of acceptable birth control methods. Information must be captured appropriately within the site's source documents. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
- Participant must agree to not breastfeed during the study or for 30 days after the last dose of study treatment.
- Ability to understand and the willingness to sign a written informed consent document.
- Tissue from a prior craniotomy or biopsy for clinical genetic sequencing (at least one FFPE block or 15 unstained slides). If CNS tissue is not available, extracranial tissue can be used for sequencing. Patients previously assessed for genetic sequencing who meet requirements of section 9.2.1 do not need to have additional tissue available for prospective genetic screening.
- Patients with progressive extracranial disease will not be excluded.
- Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
- Stable dose of corticosteroids for at least 7 days.
- Patients are allowed to remain on letrozole, anastrozole, exemestane, tamoxifen, fulvestrant, trastuzumab, bisphosphonates, denosumab or ovarian suppression therapy
- Ability to swallow capsules
Who cannot join
- Prior treatment with PARP inhibitor.
- Participants who have had chemotherapy, immunotherapy or radiotherapy within 2 weeks prior to entering the study or those who have continuing or unresolved ≥grade 2 adverse events due to agents administered more than 2 weeks earlier (except for patients who will receive letrozole, anastrozole, exemestane, tamoxifen, fulvestrant, trastuzumab, bisphosphonates, denosumab or ovarian suppression therapy).
- Participant must not have had major surgery ≤ 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects.
- Must not have received investigational therapy ≤ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior initiating protocol therapy.
- Participant has had radiation therapy encompassing >20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy.
- Participant must not have a known hypersensitivity to niraparib components or excipients.
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- Participant must not have received a transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol therapy.
- Participant must not have received colony stimulating factors (e.g., granulocyte colony-stimulating factor, granulocyte macrophage colony stimulating factor, or recombinant erythropoietin) within 4 weeks prior initiating protocol therapy.
- Participant has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted > 4 weeks and was related to the most recent treatment.
- Participant must not have any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
- Participant must not have a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent.
- Participant must not have had diagnosis, detection, or treatment of another type of cancer ≤ 2 years prior to initiating protocol therapy (except basal or squamous cell carcinoma of the skin and cervical cancer that has been definitively treated)
- Unable to undergo MRI scans.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
About this study
Official title: Genomically Guided Phase II Study to Evaluate the Clinical Benefit of Niraparib in Tumors Metastatic to the CNS
This research is being done to see how effective the drug niraparib is against cancer that has metastasized to the central nervous system (CNS).
- This research study involves the study drug niraparib.
Read the detailed description
This is a single arm open-label study designed to evaluate the efficacy and safety of niraparib in treating cancer that has metastasized to the central nervous system (CNS).
The U.S. Food and Drug Administration (FDA) has not approved niraparib for cancer metastasized to the central nervous system (CNS) but it has been approved for other uses.
Niraparib is a type of drug called a "PARP inhibitor", which blocks DNA (the genetic material of cells) damage from being repaired or may prevent damage from occurring in the first place. In cancer treatment, inhibiting PARP may help kill cancer cells by not allowing the cancer cells to repair its DNA damage or prevent DNA damage associated with your diagnosis from occurring.
The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.
Participants will receive the study drug for up to 2 years or until their disease worsens, they have unacceptable side effects, or they meet one of the criteria to be removed from the study. Participants will then be followed every 4 months for up to 2 years.
It is expected that about 20 people will take part in this research study.
GlaxoSmithKline, a pharmaceutical company, is supporting this research study by providing funding for the study, including the study drug.
- Conditions
- Metastatic Cancer, Central Nervous System Cancer
- Being tested
- Niraparib
- Keywords
- Metastatic Cancer, Central Nervous System Cancer
- Medical subject headings
- Neoplasm Metastasis, Central Nervous System Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NiraparibDrug
Also called Zejula
Capsule taken by mouth
| Study group | Role | What they receive |
|---|---|---|
| Niraparib | Experimental | Participants will receive niraparib 1x daily for each 28 day study treatment cycle up to 2 years or until disease worsens or unacceptable side effects occur. Receives: Drug: Niraparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intracranial Clinical benefit rate
Assessed by RANO criteria for brain metastases
Measured: 8 Weeks
Secondary outcomes (5)
Extracranial clinical benefit rate
Assessed by RECIST and duration of response
Measured: Up to 2 years
Intracranial disease progression
Assessed by cumulative incidence function (CIF), which estimates the marginal probability of each competing event via cause-specific hazards
Measured: Time to the first occurrence of intracranial disease progression, or death from any cause up to 2 years
Extracranial disease progression
Assessed by cumulative incidence function (CIF), which estimates the marginal probability of each competing event via cause-specific hazards
Measured: Time to the first occurrence of extracranial disease progression, or death from any cause up to 2 years
Overall Survival Rate
Summarized using Kaplan-Meier.
Measured: Up to 2 years
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0
The number and proportion of adverse events, graded as defined by CTCAE version 5.0 will be will be summarized according to system organ class and/or preferred term, severity (based on CTCAE grade), type of adverse event, and relation to study treatment.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2021
- Study start5 Apr 2022
- Primary completion1 Dec 2026 (estimated)
- Study completion1 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic CancerStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- 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
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Principal investigator, Nancy Wang, M.D., Massachusetts General Hospital
- Investigators
- Nancy Wang, MD, MPH, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04992013
- Sponsor's protocol ID
- 21-154
- Status last verified
- Jul 2026
- First submitted
- 28 Jul 2021
- Last updated
- 21 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genomically Guided Phase II Study to Evaluate the Clinical Benefit of Niraparib in Tumors Metastatic to the CNS
- ClinicalTrials.gov ID
- NCT04992013
- Acronym / sponsor ID
- 21-154
- Conditions
- Metastatic Cancer, Central Nervous System Cancer
- Keywords
- Metastatic Cancer, Central Nervous System Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- 5 Apr 2022 (actual)
- Primary completion
- 1 Dec 2026 (estimated)
- Study completion
- 1 Jun 2027 (estimated)
- First posted
- 5 Aug 2021 (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 research is being done to see how effective the drug niraparib is against cancer that has metastasized to the central nervous system (CNS).
- This research study involves the study drug niraparib.
Detailed description
This is a single arm open-label study designed to evaluate the efficacy and safety of niraparib in treating cancer that has metastasized to the central nervous system (CNS).
The U.S. Food and Drug Administration (FDA) has not approved niraparib for cancer metastasized to the central nervous system (CNS) but it has been approved for other uses.
Niraparib is a type of drug called a "PARP inhibitor", which blocks DNA (the genetic material of cells) damage from being repaired or may prevent damage from occurring in the first place. In cancer treatment, inhibiting PARP may help kill cancer cells by not allowing the cancer cells to repair its DNA damage or prevent DNA damage associated with your diagnosis from occurring.
The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.
Participants will receive the study drug for up to 2 years or until their disease worsens, they have unacceptable side effects, or they meet one of the criteria to be removed from the study. Participants will then be followed every 4 months for up to 2 years.
It is expected that about 20 people will take part in this research study.
GlaxoSmithKline, a pharmaceutical company, is supporting this research study by providing funding for the study, including the study drug.
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: NiraparibParticipants will receive niraparib 1x daily for each 28 day study treatment cycle up to 2 years or until disease worsens or unacceptable side effects occur. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (32 listed)
- Participants must have histologically or cytologically confirmed disease from any solid tumor.
- Patients must be asymptomatic or minimally symptomatic from CNS metastases for at least 7 days prior to initiation of study therapy. Minimal symptoms is defined as not requiring escalating doses of steroids or seizure medications for at least 7 days prior to initiation of study therapy.
- Participants must have measurable disease in the CNS, defined as at least one lesion that can be accurately measured in at least one dimension as ≥10 mm.
- Participants must have progressive CNS lesions, as defined by one of the following:
- Diagnosis of triple negative breast cancer or ovarian cancer, or any cancer histology with the presence of alteration in BRCA1, BRCA2, PARP metabolism, DNA repair pathways and HRD (homologous recombination deficiency) genes in the metastatic site as described in Section 9.2 using a CLIA-certified assay. Specific genetic changes in the HRD signature or DNA repair pathway include mutations in ATM, BAP1, BARD1, BRCA1, BRCA2, BRIP1, MRE11A, NBN, PALB2, RAD50, RAD51B, RAD51C, RAD51D, RAD54B, RAD54L, ATR, XRCC2, and XRCC3.
Key exclusion criteria (13 listed)
- Prior treatment with PARP inhibitor.
- Participants who have had chemotherapy, immunotherapy or radiotherapy within 2 weeks prior to entering the study or those who have continuing or unresolved ≥grade 2 adverse events due to agents administered more than 2 weeks earlier (except for patients who will receive letrozole, anastrozole, exemestane, tamoxifen, fulvestrant, trastuzumab, bisphosphonates, denosumab or ovarian suppression therapy).
- Participant must not have had major surgery ≤ 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects.
- Must not have received investigational therapy ≤ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior initiating protocol therapy.
- Participant has had radiation therapy encompassing >20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy.
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: ZejulaCapsule taken by mouth | Drug | Niraparib |
Primary outcome
Intracranial Clinical benefit rate
Time frame: 8 Weeks
Assessed by RANO criteria for brain metastases
5 secondary outcomes
Extracranial clinical benefit rate
Time frame: Up to 2 years
Intracranial disease progression
Time frame: Time to the first occurrence of intracranial disease progression, or death from any cause up to 2 years
Extracranial disease progression
Time frame: Time to the first occurrence of extracranial disease progression, or death from any cause up to 2 years
Overall Survival Rate
Time frame: Up to 2 years
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0
Time frame: Up to 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2026.
- Individual participant dataSharing planned: Yes. The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
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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.
Nancy Wang, MD, MPH principal investigator
Massachusetts General Hospital
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 Cancer and Central Nervous System Cancer, run by Massachusetts General Hospital 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 32 inclusion and 13 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: under way, not looking for participants, as of the sponsor's last update on 21 Jul 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?
This study is still under way. Results are not available in the source record yet.
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?
Intracranial Clinical benefit rate (time frame: 8 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Jul 2026.