Cancer > Niraparib

Niraparib for Brain Cancer

Recruiting in Palo Alto (17 mi)

Overseen By Priscilla K. Brastianos

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Massachusetts General Hospital

Must not be taking: PARP inhibitors

Disqualifiers: Recent chemotherapy, Major surgery, MDS, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 3 jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing niraparib, a drug that may help treat cancer that has spread to the brain and spinal cord. It works by preventing cancer cells from fixing their damaged DNA, which can help kill them. The study will include about 20 participants and will last for a significant period. Niraparib is an oral drug approved for maintenance treatment in various cancers including ovarian cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you can continue taking letrozole, anastrozole, exemestane, tamoxifen, fulvestrant, trastuzumab, bisphosphonates, denosumab, or ovarian suppression therapy. If you are on other medications, it's best to discuss with the trial team.

How does the drug Niraparib differ from other treatments for brain cancer?

Niraparib is unique because it is a PARP inhibitor, which means it works by blocking a protein that helps repair DNA damage in cancer cells, potentially making it effective for brain cancer where other treatments may not target this mechanism.

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Eligibility Criteria

This trial is for adults with solid tumors that have spread to the brain and are minimally symptomatic. Participants must have measurable CNS disease, be stable on medications, and not have had recent major surgery or blood transfusions. They should not have been treated with PARP inhibitors before and must not be pregnant or breastfeeding. A good performance status and normal organ function are required.

Inclusion Criteria

My cancer is triple negative or has specific genetic changes.

I have had brain surgery or a biopsy for genetic testing.

I agree not to donate blood during the study or for 90 days after the last treatment.

Exclusion Criteria

I haven't had significant radiation therapy affecting my bone marrow recently.

I haven't taken any colony stimulating factors in the last 4 weeks.

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

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive niraparib 1x daily for each 28-day cycle up to 2 years or until disease worsens or unacceptable side effects occur

Up to 2 years

Monthly visits for each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Every 4 months

Participant Groups

The effectiveness of niraparib, a drug designed to combat cancer in the central nervous system (CNS), is being tested. The study focuses on patients whose cancer has metastasized to the CNS, particularly those with genetic alterations related to DNA repair pathways.

Group I: Niraparib Experimental Treatment 1 Intervention

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.

Niraparib is already approved in European Union, United States, Canada for the following indications:

🇪🇺 Approved in European Union as Zejula for:

• Maintenance treatment of adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy
• Maintenance treatment of adults with platinum-sensitive relapsed high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy

🇺🇸 Approved in United States as Zejula for:

• Maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy
• Treatment of adults with advanced ovarian, fallopian tube, or primary peritoneal cancer treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD)-positive status

🇨🇦 Approved in Canada as Zejula for:

• Maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Massachusetts General Hospital Cancer Center Boston, MA

Who Is Running the Clinical Trial?

Massachusetts General Hospital Lead Sponsor

GlaxoSmithKline Industry Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Buparlisib in Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase II Trial. [2020] Phosphatidylinositol 3-kinase (PI3K) signaling is highly active in glioblastomas. We assessed pharmacokinetics, pharmacodynamics, and efficacy of the pan-PI3K inhibitor buparlisib in patients with recurrent glioblastoma with PI3K pathway activation.

2. Germany pubmed.ncbi.nlm.nih.gov

Microdialysis measurement of intratumoral temozolomide concentration after cediranib, a pan-VEGF receptor tyrosine kinase inhibitor, in a U87 glioma model. [2021] Combining anti-angiogenesis agents with cytotoxic agents for the treatment of malignant gliomas may affect the cytotoxic drug distribution by normalizing the blood-brain barrier (BBB). This study examines the intratumoral concentration of temozolomide (TMZ) in the presence and absence of the pan-VEGF receptor tyrosine kinase inhibitor, cediranib.

3. England pubmed.ncbi.nlm.nih.gov

Phase I, open-label, multicentre study of buparlisib in combination with temozolomide or with concomitant radiation therapy and temozolomide in patients with newly diagnosed glioblastoma. [2021] Most glioblastoma tumours exhibit intrinsic phosphatidylinositol 3-kinase (PI3K) pathway activation. Preclinical in vitro and in vivo models suggest that buparlisib (an oral pan-PI3K inhibitor) can have an effect on glioblastoma directly and by enhancing the activity of radiation and of temozolomide.

4. England pubmed.ncbi.nlm.nih.gov

EORTC study 26041-22041: phase I/II study on concomitant and adjuvant temozolomide (TMZ) and radiotherapy (RT) with PTK787/ZK222584 (PTK/ZK) in newly diagnosed glioblastoma. [2022] Glioblastoma is a highly vascularised tumour with a high expression of both vascular endothelial growth factor (VEGF) and VEGFR. PTK787/ZK222584 (PTK/ZK, vatalanib), a multiple VEGF receptor inhibitor, blocks the intracellular tyrosine kinase activity of all known VEGF receptors and is therefore suitable for long-term therapy of pathologic tumour neovascularisation.

5. United States pubmed.ncbi.nlm.nih.gov

Pazopanib reveals a role for tumor cell B-Raf in the prevention of HER2+ breast cancer brain metastasis. [2022] Brain metastases of breast cancer contribute significantly to patient morbidity and mortality. We have tested pazopanib, a recently approved antiangiogenic drug that targets VEGFR1, VEGFR2, VEGFR3, PDGFRβ, PDGFRα, and c-kit, for prevention of experimental brain metastases and mechanism of action.