Niraparib in Tumors Metastatic to the CNS

NCT04992013 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 21-154
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Metastatic Cancer; Central Nervous System Cancer

Keywords

Metastatic Cancer; Central Nervous System Cancer

Outcome Measures

Primary Outcomes (1)

• Intracranial Clinical benefit rate

  Assessed by RANO criteria for brain metastases

  8 Weeks

Secondary Outcomes (5)

• Extracranial clinical benefit rate

  Up to 2 years

• Intracranial disease progression

  Time to the first occurrence of intracranial disease progression, or death from any cause up to 2 years

• Extracranial disease progression

  Time to the first occurrence of extracranial disease progression, or death from any cause up to 2 years

• Overall Survival Rate

  Up to 2 years

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0

  Up to 2 years

Study Arms (1)

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.

Drug: Niraparib

Interventions

Niraparib DRUG

Capsule taken by mouth

Also known as: Zejula

Niraparib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Central Nervous System Neoplasms

Interventions

niraparib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases

Study Officials

• Priscilla Brastianos, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 28, 2021
• First Posted: August 5, 2021
• Study Start: April 5, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (1)