Description:
Evaluating the efficacy and safety of niraparib and Tumor-Treating Fields (TTFields) in
recurrent glioblastoma (GBM).
Title
- Brief Title: Niraparib/TTFields in GBM
- Official Title: A Phase II Study Evaluating the Efficacy and Safety of Niraparib and Tumor-Treating Fields in Recurrent Glioblastoma
Clinical Trial IDs
- ORG STUDY ID:
03319
- NCT ID:
NCT04221503
Conditions
- Glioblastoma
- Recurrent Glioblastoma
- GBM
Interventions
| Drug | Synonyms | Arms |
|---|
| Niraparib | ZEJULA | Cohort A |
Purpose
Evaluating the efficacy and safety of niraparib and Tumor-Treating Fields (TTFields) in
recurrent glioblastoma (GBM).
Detailed Description
Some of the study objectives will be exploratory in nature and will be published in a
narrative format instead of a quantitative analysis. This includes a comparison in disease
control rate (DCR), objective response rate (ORR), progression-free survival (PFS), and
overall survival (OS) in subjects who received previous bevacizumab versus those who have not
received prior bevacizumab. Also, comparisons of whole exome sequencing (WES)-based HRD
scores, RNAseq gene expression signatures, and RAD51 immunofluorescence between post-TTFields
surgical tumor specimens and archival pre-TTFields surgical tumor specimens will be
completed.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| 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. | |
| 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. | |
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, completed
and signed by a pathologist.
- 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.
- Implanted pacemaker, defibrillator or deep brain stimulator, other implanted
electronic devices in the brain.
- 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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 22 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Disease control, defined as achievement of either CR, PR, or SD, as defined by modified Response Assessment in Neuro-Oncology (mRANO) criteria. |
| Time Frame: | When termination of the study or 5 years after removal from protocol therapy, whichever occurs first. |
| Safety Issue: | |
| Description: | 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. |
Secondary Outcome Measures
| Measure: | Number of AEs (Adverse Events) |
| Time Frame: | When termination of the study or 5 years after removal from protocol therapy, whichever occurs first. |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Duration of disease control. |
| Time Frame: | When termination of the study or 5 years after removal from protocol therapy, whichever occurs first. |
| Safety Issue: | |
| Description: | Achieving a confirmed best response to treatment of stable disease (SD), partial response (PR), or complete response (CR). |
| Measure: | Objective radiographic response (ORR) |
| Time Frame: | When termination of the study or 5 years after removal from protocol therapy, whichever occurs first. |
| Safety Issue: | |
| Description: | ORR is defined by mRANO criteria, and duration of response. |
| Measure: | Progression-free survival (PFS) |
| Time Frame: | When termination of the study or 5 years after removal from protocol therapy, whichever occurs first. |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Overall survival (OS) |
| Time Frame: | When termination of the study or 5 years after removal from protocol therapy, whichever occurs first. |
| Safety Issue: | |
| Description: | Overall survival (OS) is defined as the time from date of enrollment until death from any cause. |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | University of Pennsylvania |
Last Updated
January 7, 2020
