This is a randomized, two-arm, open-label, phase 0 trial to assess intratumoral pharmacokinetics and pharmacodynamics of niraparib in subjects with progressive IDH1 or IDH2 mutant glioma. \- This research study involves an experimental treatment called Niraparib.
This is a randomized, two-arm, open-label, phase 0 trial to assess intratumoral pharmacokinetics and pharmacodynamics of niraparib in subjects with progressive IDH1 or IDH2 mutant glioma. * This research study involves an experimental treatment called Niraparib. * The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. * Participants will be randomized into one of two groups * Arm A: 1 cycle of Niraparib, followed by surgery, followed by up to 12 cycles of niraparib. * Arm B: Surgery followed by up to 12 cycles of niraparib Participants will receive study treatment for up to 12 Cycles (1 cycle is 28 days long) and will be followed for up to 5 years after the study treatment. It is expected that about 16 people will take part in this research study. This research study is a Pilot Study to investigate the study drug's (niraparib) activity in tumor tissue. The U.S. Food and Drug Administration (FDA) has not approved niraparib for this specific disease but it has been approved for other uses.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
16
Oral, daily, dosage per protocol,4 Weeks
The participants in both arms will resume/start on treatment with niraparib 2 -4 weeks after surgery. Treatment can be held for an additional 28 days to allow for recovery from surgery, at the investigator's discretion. Participants will continue treatment for up to 12 total cycles of treatment or until tumor progression, unacceptable toxicity or withdrawal of consent.
Massachusetts General Hospital
Boston, Massachusetts, United States
Drug concentration of niraparib
Drug concentrations of niraparib in enhancing and non-enhancing tumor tissue from subjects treated with the agent for one month prior to surgery.
Time frame: 1 year
PARP activity in resected tumors
PARP activity assessed by measuring levels of poly (ADP)-ribose (PAR)s
Time frame: 1 year
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0"
NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time frame: Up to one month after discontinuation of treatment
Median Progression-Free Survival
measured using RANO criteria for low grade glioma
Time frame: is defined as the time from randomization (or registration) to the earlier of progression or death due to any cause. Patients alive without disease progression are censored at date of last disease evaluation up to 5 years
Median Overall Survival
calculated with the Kaplan-Meier method and the Log-Rank test will be conducted to compare between the study arms
Time frame: Overall Survival (OS) is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive up to 5 years
Duration of Overall Response
ORR will be calculated as the proportion of patients that are determined to be CR, PR or SD
Time frame: one month from start of treatment (Arm A only) and 2, 4, 6 and 12 months out from start of treatment after surgery up to 5 years
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Response Rate in subjects with recurrent glioma after 1 month of treatment
measured by the Response Assessment in Neuro-Oncology (RANO) Working Group for low-grade gliomas
Time frame: 1 month
Response Rate in subjects with residual glioma after surgery
measured by the Response Assessment in Neuro-Oncology (RANO) Working Group for low-grade gliomas (only in patients with subtotal resection)
Time frame: Up to 5 years
D-2-hydroxyglutarate (2-HG) levels by MRS
D-2-hydroxyglutarate (2-HG) levels by MRS
Time frame: before and one-month post treatment with niraparib up to 3 months
Genomic profile
assessed by whole exome sequencing (WES) performed on resected tumor
Time frame: Up to 5 years