Niraparib + Radiation for Brain Tumor

Not currently recruiting at 1 trial location

Overseen By Phase 0 Navigator

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Nader Sanai

Must not be taking: Coumarin anticoagulants

Disqualifiers: Pregnancy, Active infection, Heart failure, 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 explores a new treatment using niraparib, a medication, combined with radiation to combat aggressive brain tumors like glioblastoma and recurrent gliomas with specific genetic features. The goal is to evaluate the effectiveness of niraparib alone or with radiation therapy. It seeks participants newly diagnosed with glioblastoma or those with recurrent gliomas after previous treatment, specifically with certain genetic mutations. The study aims to determine the best way to combine these treatments to manage these challenging brain tumors. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Do I need to stop my current medications to join the trial?

The protocol does not specify if you need to stop all current medications. However, if you are using coumarin-derived anticoagulants, you must discontinue them before surgery. Also, if you've had chemotherapy, a 21-day washout period is required before starting the trial.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) of at least 21 days between the last chemotherapy and the start of the study. If you are taking coumarin-derived anticoagulants, you must stop them before surgery, but other anticoagulants like heparin are allowed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that niraparib is generally well-tolerated by patients with brain tumors. In earlier studies, niraparib demonstrated promising results in reaching brain tumors and affecting their growth. Importantly, no new safety concerns have emerged.

When combined with radiation therapy, niraparib proved effective and did not introduce any new safety issues. Patients in these studies did not report unexpected side effects. This suggests that niraparib, both alone and with radiation, is generally safe for people with brain tumors.

It is important to remember that this treatment remains under study. While current results are encouraging, joining a clinical trial involves some uncertainty about long-term effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Niraparib is unique because it targets specific genetic mutations in brain tumors, like IDH1 or IDH2 mutations and ATRX loss, which are not specifically addressed by current standard treatments like temozolomide and radiation. Most standard treatments for gliomas focus broadly on killing cancer cells or slowing their growth, but niraparib, a PARP inhibitor, works by interfering with the cancer cells' ability to repair their DNA, potentially making them more vulnerable to damage. Researchers are excited about niraparib because it offers a more personalized approach, potentially enhancing the effectiveness of radiation therapy and extending periods of remission for patients with these specific genetic profiles.

What evidence suggests that this trial's treatments could be effective for brain tumors?

Research has shown that niraparib may help treat certain brain tumors, such as glioblastoma and gliomas, particularly those with specific genetic changes. Studies have found that niraparib can effectively reach the tumor and impact its growth. In this trial, participants with newly diagnosed glioblastoma will receive niraparib alongside radiation therapy, which might extend their survival. Previous research indicates that niraparib can achieve higher concentrations in brain tumor tissues compared to other similar treatments. Additionally, one study found that patients taking niraparib experienced a median time of 14.9 months before their disease progressed. These early results offer promise for those considering participation in the trials. ^{1 6 7 8 9}

Who Is on the Research Team?

Nader Sanai, MD

Principal Investigator

Chief Scientific Officer/Director of the Ivy Brain Tumor Center

Are You a Good Fit for This Trial?

Adults over 18 with newly-diagnosed glioblastoma or recurrent glioma with specific genetic mutations can join. They must have recovered from any previous chemotherapy, have normal blood pressure, adequate organ function, and not be pregnant or breastfeeding. Participants need to agree to use effective contraception and adhere to lifestyle considerations for the study duration.

Inclusion Criteria

I am not pregnant or cannot become pregnant due to surgery, menopause, or other reasons.

For females of reproductive potential: use of highly effective contraception for at least 1 month prior to treatment and agreement to use such a method during study participation and for an additional 6 months after the end of treatment administration

I am having surgery for a suspected new glioblastoma diagnosis.

Exclusion Criteria

I have been diagnosed with myelodysplastic syndrome or acute myeloid leukemia.

I haven't needed antibiotics or antivirals for an infection or high fever in the last 4 weeks.

I do not have an active infection needing IV antibiotics or a known virus like HIV or hepatitis B/C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 0

Participants receive niraparib for 4 days prior to surgical resection

1 week

1 visit (in-person)

Therapeutic Expansion

Participants receive niraparib plus standard-of-care fractionated radiotherapy or niraparib monotherapy until disease progression

6-7 weeks for radiotherapy, followed by maintenance

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Niraparib
• Radiation therapy

Trial Overview The trial is testing Niraparib in combination with standard radiotherapy for some patients (Arm A), and as a single therapy for others (Arm B). It's an open-label Phase 0 study followed by an expansion phase based on initial responses, aiming to enroll up to 42 participants across multiple centers.

How Is the Trial Designed?

Group I: Arm B: Recurrent Glioma (Grades II-IV) Experimental Treatment 1 Intervention

Participants undergoing resection of a recurrent WHO Grade II, III, or IV glioma with IDH1 or IDH2 mutation and ATRX loss will be treated with niraparib for 4 days prior to a planned surgical resection. Participants who proceed to the Expansion cohort will receive niraparib in 28d cycles after surgery.

Group II: Arm A: Presumed Newly-Diagnosed glioblastoma Experimental Treatment 2 Interventions

Participants undergoing resection for a presumed newly-diagnosed glioblastoma (WHO grade 4) will be treated with niraparib for 4 days prior to surgical resection. Participants who proceed to the therapeutic expansion phase of this study will receive niraparib in combination with radiation (60 Gy over 6-7 weeks, as per standard of care). Following radiotherapy, eligible study participants may receive niraparib maintenance treatment.

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?

Nader Sanai

Lead Sponsor

Trials

11

Recruited

440+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

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

Barrow Neurological Institute

Collaborator

Trials

27

Recruited

7,100+

Ivy Brain Tumor Center

Collaborator

Trials

12

Recruited

910+

Published Research Related to This Trial

Niraparib, a DNA damage repair inhibitor, significantly increased the sensitivity of four head and neck cancer cell lines to both photon and proton radiotherapy, suggesting it could enhance treatment effectiveness.

The study found that niraparib not only reduced colony formation in some cell lines but also increased the relative biological effectiveness (RBE) of protons compared to photons, indicating a potential advantage of proton therapy when combined with niraparib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton and photon radiosensitization effects of niraparib, a PARP-1/-2 inhibitor, on human head and neck cancer cells. Wang, L., Cao, J., Wang, X., et al.[2021]

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]

In a phase 2 study involving 36 patients with radiation-induced brain injury, 61.1% achieved a significant reduction in brain edema after 4 weeks of treatment with oral apatinib, indicating its efficacy.

Apatinib was well-tolerated, with only mild to moderate side effects reported, such as hand-foot syndrome and fatigue, and no severe treatment-related toxic effects were observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Apatinib for Radiation-induced Brain Injury Among Patients With Head and Neck Cancer: An Open-Label, Single-Arm, Phase 2 Study. He, L., Pi, Y., Li, Y., et al.[2022]

Niraparib, a PARP inhibitor, was successfully used to treat a 62-year-old woman with endometrial cancer and brain metastases, leading to 6 months of disease-free progression, highlighting its potential efficacy in this rare condition.

The drug's ability to cross the blood-brain barrier allows for higher concentrations in brain tissues, which may enhance its tumor-suppressing effects, suggesting a promising mechanism of action for treating brain metastases from endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of a patient with brain metastases from endometrial cancer using Niraparib: a case report. Wang, Q., Zhang, F., Gao, H., et al.[2021]

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]

Niraparib and Talazoparib, when combined with ionizing radiation, significantly sensitize melanoma cells to treatment, leading to increased cell death compared to radiation alone.

Healthy fibroblasts are less affected by the combination therapy than melanoma cells, indicating a potential for targeted treatment that spares normal tissue while effectively targeting cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PARP Inhibitors Talazoparib and Niraparib Sensitize Melanoma Cells to Ionizing Radiation. Jonuscheit, S., Jost, T., Gajdošová, F., 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, effectively radiosensitizes human tumor cells from lung, breast, and prostate cancers, enhancing their sensitivity to radiation regardless of their p53 status, as shown in clonogenic survival assays.

The mechanism behind this radiosensitization involves niraparib converting single strand breaks (SSBs) into lethal double strand breaks (DSBs) during DNA replication, suggesting its potential for clinical use in combination with radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib (MK-4827), a novel poly(ADP-Ribose) polymerase inhibitor, radiosensitizes human lung and breast cancer cells. Bridges, KA., Toniatti, C., Buser, CA., 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.

2. cancernetwork.com cancernetwork.com/view/prior-encouraging-data-support-further-study-of-niraparib-in-glioblastoma

Prior Encouraging Data Support Further Study of Niraparib ... Findings from a proof-of-concept study show a potential survival benefit with niraparib/radiotherapy in patients with newly diagnosed glioblastoma.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05076513

Study Details | NCT05076513 | Trial of Niraparib in ... Presence of chromosomal fusion with the cutoff CT value of 35 in niraparib treated glioma tissue with IDH and ATRX loss. 6 month progression-free survival (PFS ...

4. academic.oup.com academic.oup.com/neuro-oncology/article/26/Supplement_5/v104/7825322

P18.31.A NIRAPARIB EFFICACY IN PATIENTS WITH NEWLY ... PAR suppression after ex vivo radiation was observed in 73% of the patients (24/33). Twenty of 28 (71.4%) patients with unmethylated tumors were ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.2069

A phase 0/2 trigger trial of niraparib in patients with newly ... Niraparib achieves pharmacologically-relevant concentrations in non-enhancing, newly-diagnosed GBM tissue in excess of any other studied PARP inhibitor.

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

Niraparib efficacy in patients with newly-diagnosed ... At time of data cutoff, median progression-free survival was 11.7 months. Mature overall survival (OS) data will be reported for the first time.

7. cancernetwork.com cancernetwork.com/view/advancing-glioblastoma-research-through-a-phase-3-niraparib-trial

Advancing Glioblastoma Research Through a Phase 3 ... By evaluating treatment with niraparib, investigators look to improve historical survival rates reported with standard-of-care options among ...

8. 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, ...

9. nature.com nature.com/articles/s41598-025-18255-9

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