Niraparib/TTFields in GBM

NCT ID: NCT04221503

Last Updated: 2026-01-08

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-30
• Study Completion Date: 2026-01-31

Brief Summary

Evaluating the efficacy and safety of niraparib and Tumor-Treating Fields (TTFields) in recurrent glioblastoma (GBM).

Detailed Description

Tumor-treating fields (TTFields) causes downregulation of BRCA1 signaling and reduced deoxyribonucleic acid (DNA) double-strand break repair capacity. Tumors that are deficient in the homologous recombination DNA damage repair pathway are highly sensitive to blockade of the repair of single strand DNA breaks via poly-ADP ribose polymerase (PARP) inhibition. This is a study of niraparib, a PARP inhibitor, in combination with tumor-treating fields for recurrent glioblastoma. We hypothesize that tumor-treating fields will induce a state of "BRCAness" in the glioma tumor cells, thus sensitizing them to PARP inhibition and resulting in tumor cell death.

Conditions

Glioblastoma; Recurrent Glioblastoma; GBM

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A

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 Type: EXPERIMENTAL

Niraparib

Intervention Type: DRUG

Niraparib (\[3S\]-3-\[4-{7-(aminocarbonyl)-2H-indazol-2-yl} phenyl\] piperidine \[tosylate monohydrate salt\]) is an orally available, potent, highly selective poly (adenosine diphosphate \[ADP\]-ribose) polymerase (PARP) -1 and -2 inhibitor. The niraparib drug product is provided as 100-mg capsules filled with a dry blend of niraparib tosylate monohydrate, lactose monohydrate, and magnesium stearate in a hard gelatin capsule.

Optune

Intervention Type: DEVICE

Optune, which is manufactured by Novocure, is a portable battery or power supply operated device which produces alternating electrical fields, called tumor treatment fields ("TTFields") within the human body. TTFields are applied to the patient by electrically-insulated surface transducer arrays. TTFields disrupt the rapid cell division exhibited by cancer cells.

Cohort B

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.

Group Type: ACTIVE_COMPARATOR

Niraparib

Intervention Type: DRUG

Niraparib (\[3S\]-3-\[4-{7-(aminocarbonyl)-2H-indazol-2-yl} phenyl\] piperidine \[tosylate monohydrate salt\]) is an orally available, potent, highly selective poly (adenosine diphosphate \[ADP\]-ribose) polymerase (PARP) -1 and -2 inhibitor. The niraparib drug product is provided as 100-mg capsules filled with a dry blend of niraparib tosylate monohydrate, lactose monohydrate, and magnesium stearate in a hard gelatin capsule.

Optune

Intervention Type: DEVICE

Optune, which is manufactured by Novocure, is a portable battery or power supply operated device which produces alternating electrical fields, called tumor treatment fields ("TTFields") within the human body. TTFields are applied to the patient by electrically-insulated surface transducer arrays. TTFields disrupt the rapid cell division exhibited by cancer cells.

Planned surgical resection

Intervention Type: PROCEDURE

Surgery of supratentorial glioblastoma (GBM).

Interventions

Niraparib

Niraparib (\[3S\]-3-\[4-{7-(aminocarbonyl)-2H-indazol-2-yl} phenyl\] piperidine \[tosylate monohydrate salt\]) is an orally available, potent, highly selective poly (adenosine diphosphate \[ADP\]-ribose) polymerase (PARP) -1 and -2 inhibitor. The niraparib drug product is provided as 100-mg capsules filled with a dry blend of niraparib tosylate monohydrate, lactose monohydrate, and magnesium stearate in a hard gelatin capsule.

Intervention Type: DRUG

Optune

Optune, which is manufactured by Novocure, is a portable battery or power supply operated device which produces alternating electrical fields, called tumor treatment fields ("TTFields") within the human body. TTFields are applied to the patient by electrically-insulated surface transducer arrays. TTFields disrupt the rapid cell division exhibited by cancer cells.

Intervention Type: DEVICE

Planned surgical resection

Surgery of supratentorial glioblastoma (GBM).

Intervention Type: PROCEDURE

Other Intervention Names

ZEJULA; Tumor Treatment Fields (TTFields); Tumor Resection

Eligibility Criteria

Inclusion Criteria

• Histopathologically or molecularly (per c-IMPACT NOW criteria) proven diagnosis of glioblastoma which is recurrent following radiation therapy (prior dose must have been between 40 and 75 Gy).
• Tumor O-6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) methylation status must be available from any prior GBM tumor specimen.
• Patients must have measurable contrast-enhancing disease (defined by at least 1cm x 1cm) by magnetic resonance imaging (MRI) imaging within 28 days of starting study treatment.
• Patients may have had treatment for an unlimited number of prior relapses.
• Patients must have recovered from severe toxicity of prior therapy.
• Patients must be able to swallow oral medications.
• Karnofsky performance status >= 60.
• Life expectancy >3 months.
• Adequate hematologic parameters.
• Adequate hepatic function within 7 days prior to start of study treatment.
• Adequate renal function within 7 days prior to start of study treatment.
• Reproductive Status
• Women - negative serum or urine pregnancy test
• Men and Women - must agree to an adequate method to avoid pregnancy
• Participant must agree to not donate blood during the study or for 90 days after the last dose of niraparib.
• Participant must, in the opinion of the Investigator, be able to comply with study procedures, including use of the Optune device.
• Cohort B (surgical) patients only: patients must be undergoing surgery that is clinically indicated as determined by their care providers.
• Cohort B (surgical) patients only: patients must have a tumor tissue form indicating availability of archived tissue from a previous surgery for glioblastoma.
• Patients must be able to understand the study procedures and agree to participate in the study by providing written informed consent (or have legally authorized representative sign on patient's behalf if patient physically unable to sign consent due to neurologic deficit).

Exclusion Criteria

• Age < 22 years.
• Prior treatment with tumor-treating fields therapy (Optune) within the past 6 months.
• Prior treatment with a PARP inhibitor.
• Known history or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML).
• Patients with infratentorial tumor.
• Participant has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted > 4 weeks and was related to the most recent treatment.
• Participant must not have a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent.
• Implanted pacemaker, defibrillator or deep brain stimulator, other implanted electronic devices in the brain. Non-programmable shunts are allowed. Patients with a programmable shunt are excluded.
• Skull defects.
• Known hypersensitivity to conductive hydrogels or known hypersensitivity to niraparib components or excipients.
• Patients with gastrointestinal disorders or abnormalities that would interfere with absorption of study treatment.
• Prisoners or subjects who are involuntarily incarcerated.
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
• Participant must not be simultaneously enrolled in any interventional clinical trial.

• Minimum Eligible Age: 22 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tesaro, Inc.

INDUSTRY

Sponsor Role: collaborator

NovoCure Ltd.

INDUSTRY

Sponsor Role: collaborator

Abramson Cancer Center at Penn Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

03319

Identifier Type: -

Identifier Source: org_study_id