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

30 Participants Needed

Trial Summary

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.

What makes the treatment Niraparib + Optune unique for glioblastoma?

Niraparib + Optune is unique because it combines a drug (Niraparib) that targets cancer cell repair mechanisms with Optune, a device that uses electric fields to disrupt cancer cell division, offering a novel approach compared to traditional chemotherapy or radiation. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial tests niraparib and TTFields in patients with recurrent glioblastoma. The electric fields weaken the cancer cells, and the drug stops them from fixing themselves, leading to cell death. Tumor-Treating Fields (TTFields) is a noninvasive cancer treatment that uses low-intensity alternating electric fields to disrupt cell division and has been FDA-approved for glioblastoma.

Eligibility Criteria

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

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

2. 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]

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

Buparlisib plus carboplatin or lomustine in patients with recurrent glioblastoma: a phase Ib/II, open-label, multicentre, randomised study. [2021]

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

A Phase Ib/II, open-label, multicenter study of INC280 (capmatinib) alone and in combination with buparlisib (BKM120) in adult patients with recurrent glioblastoma. [2022]

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

Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma. [2022]