Niraparib vs Temozolomide for Brain Cancer

Recruiting at 92 trial locations

Overseen By Study Navigator

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ivy Brain Tumor Center

Must not be taking: PARP inhibitors

Disqualifiers: Metastatic disease, Pneumonitis, Cirrhosis, others

Stay on Your Current Meds You can continue your current medications while participating

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

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: 16

Duration: 6-7 weeks

450 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare the effectiveness of the drug niraparib to temozolomide (TMZ), the standard treatment for glioblastoma multiforme (GBM) with an unmethylated MGMT promoter. Researchers seek to determine if niraparib extends patient survival or delays cancer progression more effectively than TMZ. Participants will be divided into two groups: one will take niraparib, and the other will take TMZ, both alongside radiation therapy. The trial seeks individuals newly diagnosed with this specific brain cancer who have not received prior treatment other than surgery. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to groundbreaking research.

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

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you should have stable or decreased doses of dexamethasone, not exceeding 5 mg daily, within 7 days before randomization.

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

Research shows that niraparib has been tested in people with glioblastoma, a type of brain cancer. Previous studies have examined its safety and tolerability. These studies found that most people tolerated niraparib well, though some experienced side effects like nausea and tiredness, which were usually manageable.

In contrast, temozolomide (TMZ) has already received FDA approval for treating brain cancer, including glioblastoma. This approval indicates thorough testing to ensure its safety. Like any medication, it can have side effects, but TMZ is widely used and is a standard treatment.

Both treatments have evidence supporting their safety, with niraparib still under study and TMZ already well-established in cancer care. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Niraparib is unique because it is a PARP inhibitor, which means it targets an enzyme involved in repairing DNA damage in cancer cells, effectively preventing them from multiplying. This mechanism is different from standard treatments like Temozolomide, which is a chemotherapy drug that kills cancer cells by damaging their DNA. Researchers are excited about Niraparib because it offers a more selective approach, potentially leading to fewer side effects and improved outcomes for patients with brain cancer. Additionally, Niraparib's oral administration makes it easier for patients to take compared to some traditional chemotherapy methods.

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

Research has shown that niraparib, one of the treatments under study in this trial, demonstrated positive effects in early studies for glioblastoma. Specifically, one study found that patients taking niraparib lived for an average of 11.7 months without their cancer worsening. This suggests that niraparib may help slow tumor growth in some patients. Additionally, evidence indicates that niraparib can reach the tumor and alter its growth. These early results are promising and support further research into its effectiveness for brain cancer. Participants in this trial will receive either niraparib or temozolomide, another treatment option being compared. ^{1 4 5 6 7}

Who Is on the Research Team?

Nader Sanai, MD

Principal Investigator

Ivy Brain Tumor Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a new diagnosis of glioblastoma multiforme (GBM) that hasn't been treated yet, except for surgery. Participants need to be in good physical condition and not planning pregnancy or breastfeeding. They must agree to use effective contraception.

Inclusion Criteria

My diagnosis is a new brain tumor identified as GBM.

I am considered suitable for a specific radiation therapy plan.

I have enough tissue samples for further testing, or I might get approval for less.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily study medication (Niraparib or Temozolomide) while undergoing standard of care radiation therapy for 6-7 weeks

6-7 weeks

Weekly visits during radiation therapy

Adjuvant Treatment

Participants may continue to take Niraparib or Temozolomide as long as the cancer does not progress or until completion of 6 cycles of treatment

Up to 6 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Every 16 weeks on days of MRI

What Are the Treatments Tested in This Trial?

Interventions

• Niraparib
• Temozolomide

Trial Overview The study compares the effectiveness of niraparib against temozolomide (TMZ), which is standard treatment for GBM without MGMT methylation. It will assess if niraparib can extend the time before cancer worsens or improve overall survival compared to TMZ.

How Is the Trial Designed?

Group I: Arm A: Niraparib Experimental Treatment 1 Intervention

Group II: Arm B: Temozolomide Active Control 1 Intervention

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?

Ivy Brain Tumor Center

Lead Sponsor

Trials

12

Recruited

910+

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 II clinical trial involving 158 patients with newly diagnosed glioblastoma, cediranib combined with radiation and temozolomide significantly improved 6-month progression-free survival (PFS) to 46.6% compared to 24.5% for the placebo group (P = 0.005).

Although cediranib showed efficacy in prolonging PFS, it was associated with a higher incidence of grade ≥3 adverse events compared to placebo (P = 0.02), and there was no significant difference in overall survival between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NRG/RTOG 0837: Randomized, phase II, double-blind, placebo-controlled trial of chemoradiation with or without cediranib in newly diagnosed glioblastoma. Batchelor, TT., Won, M., Chakravarti, A., et al.[2023]

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]

Combining temozolomide with radiotherapy significantly improves the overall response rate (ORR) in patients with brain metastases, particularly in those with non-small cell lung cancer, with a risk ratio of 1.35.

However, this combination treatment does not lead to significant improvements in progression-free survival (PFS) or overall survival (OS) and is associated with a higher incidence of side effects compared to radiotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Temozolomide and Radiotherapy on Brain Metastatic Tumor: A Systematic Review and Meta-Analysis. Ma, W., Li, N., An, Y., et al.[2018]

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 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, 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 significantly extends progression-free survival in patients with newly diagnosed advanced ovarian cancer, showing efficacy in both homologous-recombination deficiency positive (HRd) and negative (HRp) populations, based on a phase III trial.

The treatment has a manageable safety profile, with myelosuppression as the main concern, which can be effectively managed through monitoring and individualized dosing based on weight and platelet count.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib: A Review in First-Line Maintenance Therapy in Advanced Ovarian Cancer. Lee, A.[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]

Temozolomide is a chemotherapeutic agent that effectively crosses the blood-brain barrier and has shown a good safety profile in treating brain metastases from solid tumors, with clinical activity observed in heavily pretreated patients.

In a randomized phase II trial, temozolomide combined with radiation therapy resulted in a significantly higher objective response rate (96% vs. 67%) compared to radiation alone, particularly benefiting patients with newly diagnosed brain and lung metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide for treating brain metastases. Abrey, LE., Christodoulou, C.[2019]

In a phase 2 trial involving 25 patients with 1 to 4 brain metastases, temozolomide was used alongside radiosurgery, resulting in a 1-year risk of distant brain failure (DBF) of 37%, indicating a relatively low risk in the nonmelanoma subgroup.

The study suggests that patient selection factors may have influenced the low DBF risk observed, rather than the efficacy of temozolomide itself, highlighting the need for careful consideration of these factors in future trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 study of radiosurgery and temozolomide for patients with 1 to 4 brain metastases. Fiveash, JB., Arafat, WO., Naoum, GE., et al.[2020]

Temozolomide effectively prevented the formation of brain metastases from breast cancer cells that do not express the MGMT enzyme, demonstrating a dose-dependent efficacy in experimental models with complete prevention at higher doses.

The study found that temozolomide was ineffective in preventing brain metastases in cells that express MGMT, highlighting the importance of MGMT status in determining treatment outcomes and suggesting a need for further clinical investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profound prevention of experimental brain metastases of breast cancer by temozolomide in an MGMT-dependent manner. Palmieri, D., Duchnowska, R., Woditschka, S., et al.[2021]

Cediranib, a potent receptor tyrosine kinase inhibitor, did not enhance the effectiveness of radiation therapy in glioblastoma models but significantly improved the effectiveness of temozolomide (TMZ) treatment.

The study involved U87 glioblastoma xenografts expressing either the wild-type EGFR or the mutant EGFRvIII, and the combination of cediranib with TMZ suggests a promising new treatment strategy for better tumor control in glioblastoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cediranib enhances control of wild type EGFR and EGFRvIII-expressing gliomas through potentiating temozolomide, but not through radiosensitization: implications for the clinic. Wachsberger, PR., Lawrence, RY., Liu, Y., et al.[2021]

In a phase II trial involving 115 patients with non-small-cell lung cancer (NSCLC) and treated brain metastases, the addition of bevacizumab to chemotherapy or erlotinib showed a low incidence of serious CNS hemorrhage, with no cases of grade 2 or higher reported among 106 safety-evaluable patients.

The study suggests that bevacizumab is safe for use in this patient population, as it was well-tolerated with a median treatment duration of 6.3 months and only a small percentage of patients (24.5%) discontinuing due to adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of bevacizumab in patients with non-small-cell lung cancer and brain metastases. Socinski, MA., Langer, CJ., Huang, JE., et al.[2022]

The study analyzed data from the SEER database for glioblastoma patients diagnosed between 2000 and 2009, revealing that the introduction of temozolomide (TMZ) significantly reduced the odds of death by 12% at 6 months and 36% at 1 year after diagnosis compared to the pre-TMZ era.

The addition of bevacizumab (BZM) to TMZ further improved survival rates, with a 31% reduction in odds of death at 6 months and 50% at 1 year, indicating that combining these treatments offers enhanced benefits for glioblastoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Odds of death after glioblastoma diagnosis in the United States by chemotherapeutic era. Wachtel, MS., Yang, S.[2021]

Citations

1. 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.

2. 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 ...

3. 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, ...

4. 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 ...

5. 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.

6. 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 ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06258018?term=AREA%5BInterventionSearch%5D(TEMODAL)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=3

Niraparib and Temozolomide in Patients Glioblastoma The study evaluates safety, tolerability, pharmacokinetics at recommended phase II dose (RP2D) and preliminary antitumor activity of Niraparib + dd-TMZ "one ...