Niraparib for Recurrent Brain Cancer

Overseen By Isabel Arrillaga-Romany, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Massachusetts General Hospital

Must not be taking: Lomustine, Investigational agents

Disqualifiers: Pregnancy, HIV, Hepatitis B/C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an experimental treatment called Niraparib for individuals with recurrent brain cancer that has a specific gene mutation (IDH1 or IDH2). The trial aims to observe Niraparib's behavior inside the tumor and its effects on cancer cells. Participants will be divided into two groups: one will receive Niraparib before surgery, while the other will not, though both groups will eventually receive the treatment. This trial seeks individuals with glioma who have experienced cancer recurrence and can undergo surgery. As an Early Phase 1 trial, this research focuses on understanding how Niraparib works in people, offering participants the opportunity to be among the first to receive this new treatment.

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 must not have received systemic anticancer therapy or certain investigational agents within 28 days before starting the study drug. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that Niraparib has undergone safety testing in various studies. In one study, some patients with newly diagnosed brain cancer experienced thrombocytopenia, a decrease in blood cells that aid in clotting. Although serious, this issue resolved without further complications.

Another study examined Niraparib for high-grade brain tumors, assessing the drug's efficacy and side effects. These study results help researchers better understand Niraparib's safety.

While Niraparib is still under investigation for brain cancer, it has FDA approval for other conditions, providing some insight into its safety. However, as this trial is in its early stages, researchers are still learning about its full safety profile for this specific condition. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Niraparib is unique because it targets cancer cells by inhibiting a specific enzyme called PARP, which is involved in repairing DNA damage. Unlike traditional treatments for recurrent brain cancer that primarily focus on surgery, radiation, or chemotherapy, niraparib's mechanism allows it to disrupt cancer cell repair and potentially enhance the effectiveness of other treatments. Researchers are excited about niraparib because it offers a new approach that might slow tumor growth and improve patient outcomes, especially in cases where other treatments have failed.

What evidence suggests that Niraparib might be an effective treatment for recurrent brain cancer?

Research has shown that niraparib may help treat brain tumors such as glioma. In this trial, participants in Arm A will receive niraparib daily before undergoing tumor resection, while those in Arm B will not receive niraparib prior to surgery. Studies have found that niraparib can reach the brain and slow tumor growth in glioblastoma, a type of brain cancer. It accumulates in brain tissue more effectively than other similar treatments, suggesting it might better target brain tumors. Early results indicate that niraparib might shrink tumors in patients with high-grade glioma, offering hope for those with recurring brain cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

Isabel Arrillaga-Romany, MD, Ph.D

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

Adults with confirmed IDH1/2 mutant glioma, evidence of tumor progression, and a Karnofsky Performance Score (KPS) ≥ 70. Must be at least 12 weeks post-CNS radiation, not pregnant or breastfeeding, agree to contraception use, have adequate organ function and no major surgery within the last 4 weeks. Cannot be on other clinical trials or have had certain treatments recently.

Inclusion Criteria

Participant must agree to not breastfeed during the study or for 30 days after the last dose of study treatment.

It has been over 12 weeks since I completed radiation therapy to my brain.

- Hemoglobin ≥ 9 g/dL

Exclusion Criteria

Participants who are pregnant or breast-feeding.

Participants with any other medical or psychological condition, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate, or participate in the study.

Participants with known hypersensitivity to any of the components of niraparib.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment - Arm A

Participants receive 1 cycle of Niraparib followed by surgery, then up to 12 cycles of Niraparib

13 cycles (1 cycle is 28 days)

Monthly visits for each cycle

Treatment - Arm B

Participants undergo surgery followed by up to 12 cycles of Niraparib

12 cycles (1 cycle is 28 days)

Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Niraparib
• Resection/Treatment with Niraparib

Trial Overview The trial is testing Niraparib's effects directly in the brain tumors of patients with progressive IDH1/2 mutant gliomas. It's an open-label phase 0 study where participants will undergo resection/treatment to assess how well Niraparib works inside these tumors.

How Is the Trial Designed?

Group I: Arm A Treatment with Niraparib Experimental Treatment 2 Interventions

Patients randomized to arm A will receive niraparib daily and undergo tumor resection after 28 days (+/- 7 days) of treatment. The participants in both arms will resume/start on treatment with niraparib 2 -4 weeks after surgery . Participants will continue treatment for up to 12 total cycles of treatment or until tumor progression, unacceptable toxicity or withdrawal of consent

Group II: Arm B No Treatment with Niraparib Active Control 1 Intervention

Subjects in arm B will not receive niraparib prior to surgery. The participants in both arms will resume/start on treatment with niraparib 2 -4 weeks after surgery . Participants will continue treatment for up to 12 total cycles of treatment or until tumor progression, unacceptable toxicity or withdrawal of consent.

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

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Published Research Related to This Trial

In a phase Ib/II study involving 35 patients with recurrent glioblastoma, the maximum tolerable dose (MTD) of the pan-PI3K inhibitor buparlisib was established at 100 mg per day when combined with carboplatin, showing a consistent safety profile without new safety concerns.

However, the combination of buparlisib with either carboplatin or lomustine did not demonstrate sufficient antitumor activity compared to historical data for these single-agent treatments, indicating limited efficacy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buparlisib plus carboplatin or lomustine in patients with recurrent glioblastoma: a phase Ib/II, open-label, multicentre, randomised study. Rosenthal, M., Clement, PM., Campone, M., et al.[2021]

Niraparib has been approved by the FDA for patients with complete or partial response to first-line platinum-based chemotherapy, regardless of their BRCAm or HRD status, expanding treatment options for more patients.

Olaparib, in combination with bevacizumab, has also received FDA approval for patients with epithelial ovarian cancer, indicating that PARP inhibitors are now beneficial not only for BRCAm and HRD-deficient patients but also for those with HRD-proficient tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PARP inhibitors in the treatment of ovarian cancer: a review. Washington, CR., Moore, KN.[2023]

Gefitinib, a medication used for non-small-cell lung cancer (NSCLC), has shown clinical activity in some patients with brain metastases, leading to improvements in neurological and systemic symptoms.

Case studies indicate that gefitinib can result in partial and even complete responses in brain metastases, suggesting the need for larger trials to better understand its efficacy and potential role in treatment, especially in combination with radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality-of-life benefits and evidence of antitumour activity for patients with brain metastases treated with gefitinib. Katz, A., Zalewski, P.[2018]

In a phase III trial involving patients with advanced breast cancer and germline BRCA1/2 mutations, niraparib showed a median progression-free survival (PFS) of 4.1 months compared to 3.1 months for physician's choice chemotherapy, although the difference was not statistically significant (P = 0.86).

Despite the trial being halted due to issues with data assessment, niraparib demonstrated a 35% objective response rate, indicating its potential effectiveness in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib for Advanced Breast Cancer with Germline BRCA1 and BRCA2 Mutations: the EORTC 1307-BCG/BIG5-13/TESARO PR-30-50-10-C BRAVO Study. Turner, NC., Balmaña, J., Poncet, C., et al.[2023]

Niraparib, a PARP inhibitor, is recommended as a maintenance treatment for patients with platinum-sensitive relapsed ovarian cancer, leveraging the concept of synthetic lethality in BRCA mutation carriers.

A case study of a 68-year-old woman with brain metastases from high-grade serous ovarian cancer showed that she remained free of disease progression for over 17 months while on niraparib after second-line chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib as maintenance therapy in a patient with ovarian cancer and brain metastases. Gray, S., Khor, XY., Yiannakis, D.[2021]

Niraparib, a treatment for recurrent ovarian cancer, has a high dose reduction rate of 68.9% due to treatment-emergent adverse events, with thrombocytopenia being a notable cause for 3.3% of patients.

Baseline body weight and platelet count are significant predictors for the risk of severe thrombocytopenia, suggesting that patients with a body weight under 77 kg or platelet count below 150,000/µl may benefit from starting at a lower dose of 200 mg/day without compromising progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and dose modification for patients receiving niraparib. Berek, JS., Matulonis, UA., Peen, U., et al.[2021]

Niraparib, a recently approved treatment for recurrent platinum-sensitive ovarian cancer, has demonstrated a high oral bioavailability of 72.7% in humans, indicating effective absorption when taken orally.

The study involved six patients who received a therapeutic dose of 300 mg of niraparib, followed by a small intravenous dose to measure its levels in the bloodstream, confirming its potential as a convenient oral treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of the absolute oral bioavailability of niraparib by simultaneous administration of a 14C-microtracer and therapeutic dose in cancer patients. van Andel, L., Rosing, H., Zhang, Z., et al.[2019]

Niraparib, a PARP inhibitor, significantly improves progression-free survival in patients with advanced epithelial ovarian cancer, but nearly all patients (≥99%) experience treatment-emergent adverse events, with 51-74% experiencing severe (grade ≥3) events.

An individualized starting dose of niraparib based on body weight and platelet count leads to fewer severe adverse events and dose modifications, suggesting a tailored approach can enhance safety while maintaining treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and management of niraparib monotherapy in ovarian cancer clinical trials. Monk, BJ., González-Martin, A., Buckley, L., et al.[2023]

In a phase III clinical trial involving 325 patients with recurrent glioblastoma, cediranib did not significantly improve progression-free survival compared to lomustine alone, whether used as a monotherapy or in combination.

Despite not meeting the primary endpoint, cediranib demonstrated some clinical benefits in secondary outcomes, such as delaying neurological deterioration and reducing the need for corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. Batchelor, TT., Mulholland, P., Neyns, B., et al.[2022]

Pazopanib significantly reduced the size of brain metastases in breast cancer models, showing a 73% decline in large metastases and a 39% decline in micrometastases, indicating its efficacy in preventing brain metastasis formation.

The drug acts directly on tumor cells by inhibiting B-Raf activation, which is crucial for cancer cell proliferation, suggesting a new mechanism of action for pazopanib beyond its known antiangiogenic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pazopanib reveals a role for tumor cell B-Raf in the prevention of HER2+ breast cancer brain metastasis. Gril, B., Palmieri, D., Qian, Y., et al.[2022]

In a Phase 2 study involving 20 Japanese women with heavily pretreated ovarian cancer, niraparib demonstrated an objective response rate of 35%, indicating that it can effectively reduce tumor size in some patients.

The treatment was generally well-tolerated, with a high disease control rate of 90%, although common side effects included anemia and nausea, and 70% of patients experienced dose reductions or interruptions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 single-arm study on the efficacy and safety of niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer. Okamoto, A., Kondo, E., Nakamura, T., et al.[2021]

In a study involving seven nude rats with gliomas, the combination of the anti-angiogenesis agent cediranib with the chemotherapy drug temozolomide (TMZ) resulted in a slight increase in the intratumoral concentration of TMZ, suggesting improved drug delivery to the tumor.

The MRI results indicated that cediranib treatment led to a normalization of the blood-brain barrier, which may enhance the effectiveness of chemotherapy in treating malignant gliomas.

NCBI (Pubmed)

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. Grossman, R., Tyler, B., Rudek, MA., et al.[2021]

Citations

1. ivybraintumorcenter.org ivybraintumorcenter.org/gliofocus-glioblastoma-clinical-study/

Gliofocus - Phase 3 Study of Niraparib for Glioblastoma The drug showed significant results in reaching the tumor and changing how the cancer grew. Electricity spreading out like neurons. Published Research. Below ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS2096

A global phase 3, open-label, randomized 2-arm study ... Secondary endpoints include overall response rate, health-related quality of life, neurocognitive function, and the safety and tolerability of ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2002

Niraparib efficacy in patients with newly-diagnosed ... Niraparib achieves pharmacologically relevant concentrations in non-enhancing, newly-diagnosed GBM tissue in excess of any other studied PARP inhibitor.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12480552/

Assessment of brain penetration and tumor accumulation of ... These data provide evidence that niraparib may offer a better PK exposure profile than olaparib in primary and secondary brain tumors. Moreover, ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-04404

Niraparib for the Treatment of Recurrent High Grade Glioma This phase II trial tests the safety and side effects of niraparib and whether it works to shrink tumors in patients with high grade brain tumor (glioma) ...

6. zejula.com zejula.com/about/clinical-trial-results/

Clinical Trial Results | ZEJULA (niraparib) ZEJULA has been studied in a trial called PRIMA, which measured median progression-free survival, or mPFS, in patients who tested positive for HRD.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06388733

NCT06388733 | A Study Comparing Niraparib With ... The goal of this Phase 3 clinical trial is to compare the efficacy of niraparib versus temozolomide (TMZ) in adult participants with newly-diagnosed, ...