Niraparib/TTFields in GBM

NCT04221503 | Active Not Recruiting Phase 2 FDA Drug FDA Device

• 1 other identifier: 03319
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Glioblastoma; Recurrent Glioblastoma; GBM

Outcome Measures

Primary Outcomes (1)

• Disease control, defined as achievement of either CR, PR, or SD, as defined by modified Response Assessment in Neuro-Oncology (mRANO) criteria.

  Complete response (CR) is seen as the disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks. Partial response (PR) is ≥50% decrease in sum of products of perpendicular diameters or ≥65% decrease in total volume of all measurable enhancing lesions compared with baseline, sustained for at least 4 weeks. Stable disease (SD), must be present on two consecutive MRI scans, with the 2nd/confirmatory MRI performed at least 16 weeks after starting treatment.

  When termination of the study or 5 years after removal from protocol therapy, whichever occurs first.

Secondary Outcomes (5)

• Number of AEs (Adverse Events)

  When termination of the study or 5 years after removal from protocol therapy, whichever occurs first.

• Duration of disease control.

  When termination of the study or 5 years after removal from protocol therapy, whichever occurs first.

• Objective radiographic response (ORR)

  When termination of the study or 5 years after removal from protocol therapy, whichever occurs first.

• Progression-free survival (PFS)

  When termination of the study or 5 years after removal from protocol therapy, whichever occurs first.

• Overall survival (OS)

  When termination of the study or 5 years after removal from protocol therapy, whichever occurs first.

Other Outcomes (3)

• Objective response rate (ORR) associations.

  When termination of the study or 5 years after removal from protocol therapy, whichever occurs first.

• Progression-free survival (PFS) associations

  When termination of the study or 5 years after removal from protocol therapy, whichever occurs first.

• Overall survival (OS) associations

  When termination of the study or 5 years after removal from protocol therapy, whichever occurs first.

Study Arms (2)

Cohort A

EXPERIMENTAL

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.

Drug: Niraparib; Device: Optune

Cohort B

ACTIVE COMPARATOR

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.

Drug: Niraparib; Device: Optune; Procedure: Planned surgical resection

Interventions

Niraparib 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.

Also known as: ZEJULA

Cohort A; Cohort B

Optune 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.

Also known as: Tumor Treatment Fields (TTFields)

Cohort A; Cohort B

Planned surgical resection PROCEDURE

Surgery of supratentorial glioblastoma (GBM).

Also known as: Tumor Resection

Cohort B

Eligibility Criteria

• Age: 22 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead
• Tesaro, Inc.: collaborator
• NovoCure Ltd.: collaborator

Study Sites (1)

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

niraparib; Transurethral Resection of Bladder

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2019
• First Posted: January 9, 2020
• Study Start: December 30, 2019
• Primary Completion: January 1, 2026
• Study Completion: January 1, 2026
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)