Niraparib + Optune for Glioblastoma

Overseen By Maikel Mansour

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Pennsylvania

Must not be taking: PARP inhibitors

Disqualifiers: Age < 22, MDS/AML, others

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

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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of combining a drug called niraparib with a device called Tumor-Treating Fields (TTFields) for treating glioblastoma, a type of brain cancer that has returned after initial treatment. The trial includes two groups: one for patients not needing surgery and another for those requiring surgery. Suitable candidates typically have recurrent glioblastoma and have already undergone radiation therapy. They should be able to swallow pills and use a device on their head. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research has shown that niraparib has been tested for safety in treating glioblastoma. In one study, patients found the drug to be generally safe and well-tolerated. Other studies have examined niraparib in combination with other treatments, showing it can reach cancer cells and affect their growth.

For Tumor-Treating Fields (TTFields), research indicates they are generally safe. Serious side effects were rare, with less than 1% directly linked to TTFields. In treatments for newly diagnosed glioblastoma, TTFields were well-tolerated, but their effects on recurring cases like this one are less clear. However, real-world data supports that TTFields remain safe in practice.

These findings suggest both niraparib and TTFields are generally safe for humans. As this trial continues, it will provide more specific safety information for their combined use in recurrent glioblastoma. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Niraparib + Optune is unique because it combines a targeted therapy with an innovative device to tackle glioblastoma, a notoriously aggressive brain cancer. Niraparib is a PARP inhibitor, which works by interfering with cancer cells' ability to repair their DNA, potentially leading to their death. Optune, on the other hand, uses electric fields to disrupt cancer cell division. This combination approach is promising because it targets the tumor in two distinct ways, offering a potential advantage over traditional treatments like surgery, radiation, and chemotherapy. Researchers are excited about this treatment because it might improve outcomes for patients who have limited options with current standard therapies.

What evidence suggests that niraparib and Optune might be effective for glioblastoma?

This trial will evaluate the combination of Niraparib and Optune for glioblastoma. Research has shown that niraparib can effectively reach glioblastoma tumors, potentially improving patient outcomes. In one study, patients with newly diagnosed glioblastoma who took niraparib lived without their cancer worsening for an average of 14.9 months and had an overall survival of 20.3 months. This suggests that niraparib might help slow tumor growth and extend life.

Regarding Optune, studies have found it can improve survival rates for people with recurring glioblastoma. In a large trial, patients using Optune lived longer at both 2 and 5 years compared to those who didn't use it. Additionally, Optune was associated with longer periods where the cancer did not worsen, indicating it may help keep the cancer from progressing for a longer time. Participants in this trial will be divided into two cohorts: Cohort A will receive TTFields therapy with Optune before starting niraparib, while Cohort B will receive TTFields therapy with Optune before and after surgical resection, followed by niraparib. ^{2 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults over 22 with recurrent glioblastoma after radiation therapy. They must understand and consent to the study, have measurable disease by MRI, be in stable health with a life expectancy over 3 months, and agree to contraception. Excluded are those with certain blood disorders, prior Optune use within 6 months, hypersensitivity to treatment components or severe medical conditions.

Inclusion Criteria

My blood test results are within normal ranges.

I have a form showing I can provide tissue from my past brain tumor surgery.

I am in Cohort B and my doctor has determined I need surgery.

Exclusion Criteria

I have a defect in my skull.

I have not used Optune therapy in the last 6 months.

My tumor is located in the lower part of my brain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Treatment

Participants in Cohort A initiate TTFields therapy for 5-7 days prior to starting niraparib. Participants in Cohort B receive TTFields for 5-7 days prior to planned surgical resection, undergo surgical resection, resume TTFields postoperatively, and initiate niraparib 5-7 days after starting TTFields postoperatively.

5-7 days

Treatment Continuation

Participants continue with niraparib and TTFields therapy. Monitoring for disease control and adverse events.

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments for disease control and survival outcomes.

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Niraparib
• Optune

Trial Overview The trial tests niraparib's effectiveness combined with Tumor-Treating Fields (TTFields) on recurrent glioblastoma. It includes patients who've had multiple relapses and measures safety alongside efficacy of this combination therapy.

How Is the Trial Designed?

Group I: Cohort A Experimental Treatment 2 Interventions

Cohort A is for subjects with recurrent glioblastoma who do not have clinical indication for surgical resection of the recurrent tumor. Subjects in Cohort A will initiate and continue TTFields therapy for 5-7 days prior to starting niraparib.

Group II: Cohort B Active Control 3 Interventions

Cohort B is for subjects with recurrent glioblastoma who have a clinical indication for surgical resection of the recurrent tumor. Subjects in Cohort B will receive TTFields for 5-7 days prior to planned surgical resection, undergo surgical resection, resume TTFields postoperatively, and initiate niraparib 5- 7 days after starting TTFields postoperatively.

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?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Tesaro, Inc.

Industry Sponsor

Trials

57

Recruited

10,600+

NovoCure Ltd.

Industry Sponsor

Trials

64

Recruited

6,100+

Ashley Cordova

NovoCure Ltd.

Chief Executive Officer

Bachelor of Science in Material Engineering from Ben-Gurion University of the Negev, Israel

Uri Weinberg

NovoCure Ltd.

Chief Medical Officer since 2020

MD from an unspecified institution

Published Research Related to This Trial

In a phase II trial involving 65 patients with recurrent glioblastoma, the pan-PI3K inhibitor buparlisib showed minimal efficacy as a single agent, with only 8% of patients achieving 6-month progression-free survival.

Despite demonstrating significant brain penetration and some reduction in PI3K pathway activity in tumor tissue, the incomplete blockade of the pathway likely contributed to the lack of clinical effectiveness, suggesting that more effective PI3K inhibitors may be needed.

NCBI (Pubmed)

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. Wen, PY., Touat, M., Alexander, BM., et al.[2020]

In a phase I study involving patients with newly diagnosed glioblastoma, the maximum tolerated dose (MTD) of buparlisib when combined with temozolomide was determined to be 80 mg/day, but the MTD for the combination with both temozolomide and radiotherapy could not be established due to significant dose-limiting toxicities.

The study reported high rates of adverse events, particularly nausea and fatigue, leading to treatment discontinuations, which contributed to Novartis's decision to halt further development of buparlisib for this indication.

NCBI (Pubmed)

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. Wen, PY., Rodon, JA., Mason, W., et al.[2021]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11485802/

P18.31.A NIRAPARIB EFFICACY IN PATIENTS WITH ... Niraparib achieves pharmacologically relevant concentrations in non-enhancing, newly-diagnosed GBM tissue in excess of any other studied PARP inhibitor.

2. 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.

3. 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 ...

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

P18.31.A NIRAPARIB EFFICACY IN PATIENTS WITH NEWLY ... Median progression-free survival was 14.9 months and median overall survival was 20.3 months. CONCLUSIONS. Niraparib achieves pharmacologically ...

5. 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.

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

A global phase 3, open-label, randomized 2-arm study ... A global phase 3, open-label, randomized 2-arm study comparing the clinical efficacy and safety of niraparib with temozolomide in adult ...

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 ...

8. 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 ...