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| Name | Class |
|---|---|
| Tesaro, Inc. | INDUSTRY |
| NovoCure Ltd. | INDUSTRY |
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Evaluating the efficacy and safety of niraparib and Tumor-Treating Fields (TTFields) in recurrent glioblastoma (GBM).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of AEs (Adverse Events) | Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0, all events will be recorded from the time a subject has signed the informed consent form. | When termination of the study or 5 years after removal from protocol therapy, whichever occurs first. |
| Measure | Description | Time Frame |
|---|---|---|
| Objective response rate (ORR) associations. | Association between pre-treatment tumor genomics, transcriptomics, proteomics, and prior bevacizumab use and ORR. | When termination of the study or 5 years after removal from protocol therapy, whichever occurs first. |
| Progression-free survival (PFS) associations |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital of the University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
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| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
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| ID | Term |
|---|---|
| C545685 | niraparib |
| D000094463 | Transurethral Resection of Bladder |
| ID | Term |
|---|---|
| D013520 | Urologic Surgical Procedures |
| D013519 | Urogenital Surgical Procedures |
| D013514 | Surgical Procedures, Operative |
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| 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. |
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| Planned surgical resection | Procedure | Surgery of supratentorial glioblastoma (GBM). |
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| Duration of disease control. |
Achieving a confirmed best response to treatment of stable disease (SD), partial response (PR), or complete response (CR). |
| When termination of the study or 5 years after removal from protocol therapy, whichever occurs first. |
| Objective radiographic response (ORR) | ORR is defined by mRANO criteria, and duration of response. | When termination of the study or 5 years after removal from protocol therapy, whichever occurs first. |
| Progression-free survival (PFS) | Progression-free survival (PFS) is defined as the time from date of enrollment until the earliest date of disease progression (as determined by mRANO criteria) or death due to any cause. | When termination of the study or 5 years after removal from protocol therapy, whichever occurs first. |
| Overall survival (OS) | Overall survival (OS) is defined as the time from date of enrollment until death from any cause. | When termination of the study or 5 years after removal from protocol therapy, whichever occurs first. |
Association between pre-treatment tumor genomics, transcriptomics, proteomics, and prior bevacizumab use and PFS. |
| When termination of the study or 5 years after removal from protocol therapy, whichever occurs first. |
| Overall survival (OS) associations | Association between pre-treatment tumor genomics, transcriptomics, proteomics, and prior bevacizumab use and OS. | When termination of the study or 5 years after removal from protocol therapy, whichever occurs first. |
| D009373 |
| Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |