Trial of Niraparib in Participants With Newly-diagnosed Glioblastoma and Recurrent Glioma

  • STATUS
    Recruiting
  • End date
    Oct 17, 2024
  • participants needed
    42
  • sponsor
    Nader Sanai
Updated on 17 December 2021
platelet count
renal function
measurable disease
IDH2
neutrophil count
EGFR
recurrent glioma

Summary

This is an open-label, multi-center Phase 0 study with an expansion phase that will enroll up to 24 participants with newly-diagnosed glioblastoma and up to 18 recurrent glioma participants with IDH mutation and ATRX loss. The trial will be composed of a Phase 0 component (subdivided into Arm A and B) and a therapeutic expansion phase. Patients with tumors demonstrating a positive PK Response (in Arm A) or a positive PD Response (in Arm B) of the Phase 0 component of the study will graduate to a therapeutic expansion phase that combines therapeutic dosing of niraparib plus standard-of-care fractionated radiotherapy (in Arm A) or niraparib monotherapy (in Arm B) until progression of disease.

Details
Condition Glioblastoma, Glioblastoma Multiforme, Glioma, GBM, Glioma, Malignant, Glioblastoma Multiforme of Brain
Treatment radiation therapy, Niraparib
Clinical Study IdentifierNCT05076513
SponsorNader Sanai
Last Modified on17 December 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Arm A participants undergoing resection for a suspected newly diagnosed glioblastoma. For Arm B, participants undergoing resection who have had a prior resection of histologically diagnosed WHO grade II-IV glioma with IDH1 or IDH2 mutation and ATRX loss
Arm A participants must have measurable disease preoperatively, defined as at least 1 contrast-enhancing lesion, with 2 perpendicular measurements of at least 1 cm
Ability to understand and the willingness to sign a written informed consent document (personally or by the legally authorized representative, if applicable)
Participant has voluntarily agreed to participate by giving written informed consent (personally or via legally authorized representative(s), and assent if applicable). Written informed consent for the protocol must be obtained prior to any screening procedures. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness
Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other procedures
Age ≥18 at time of consent
Have a performance status (PS) of ≤2 on the Eastern Cooperative Oncology (Group (ECOG) scale (Oken et al. 1982)
Ability to swallow oral medications
Confirmed negative serum pregnancy test (β-hCG) before starting study treatment or participant who is no longer of childbearing potential due to surgical, chemical, or natural menopause. If the serum pregnancy test is completed > 7 days from Day 1, a urine pregnancy test will be done to confirm a negative result prior to Day 1 dose administration
For females of reproductive potential: use of highly effective contraception for at least 1 month prior to treatment and agreement to use such a method during study participation and for an additional 6 months after the end of treatment administration
For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner and for an additional 3 months after the end of treatment administration. Avoid sperm donation for duration of the study and for an additional 6 months after the end of treatment administration
Agreement to adhere to Lifestyle Considerations throughout study duration
Participants who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to Day 1. A washout period of at least 21 days is required between last chemotherapy and Day 1
Females of child-bearing potential must agree not to breastfeed starting at screening, throughout the study period and for 6 months after final study drug administration
Participant has normal blood pressure or adequately treated and controlled hypertension (Defined as systolic BP ≤140 mmHg and diastolic BP ≤90 mmHg)
Participant has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by the local laboratory for eligibility)
Adequate Bone Marrow Function
Absolute Neutrophil Count ≥1,500/mcL
Platelets (at time of surgery) ≥100,000/mcL
Hemoglobin ≥9.0 g/dL. Participants may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion
Adequate Hepatic Function
Total Bilirubin ≤1.5 X ULN. Participants with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted
AST(SGOT) ≤2.5 X institutional ULN
ALT(SGPT) ≤2.5 X institutional ULN
Adequate Renal Function
Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 by Chronic Disease Epidemiology Collaboration (CKD-EPI) equation
INR ≤1.5 x ULN

Exclusion Criteria

Current use of coumarin-derived anticoagulant for treatment, prophylaxis or otherwise, that cannot be discontinued prior to surgery. Therapy with heparin, low molecular weight heparin (LMWH) or fondaparinux is allowed
Pregnancy or lactation
Known allergic reactions to components of the niraparib tablet, including FD&C Yellow No. 5
Active infection or fever >38.5°C requiring systemic antibiotic, antifungal or antiviral therapy within 4 weeks of Day 1
Known to have active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis as determined by the investigator
Known active systemic bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]. Screening is not required for enrollment
Any of the following cardiovascular criteria
Current evidence of cardiac ischemia
Current symptomatic pulmonary embolism
Acute myocardial infarction ≤ 6 months prior to Day 1
Heart failure of New York Heart Association Classification III or IV ≤ 6 months prior to Day 1 (Appendix 13.2)
Grade ≥ 2 ventricular arrhythmia ≤ 6 months prior to Day 1
Cerebral vascular accident (CVA) or transient ischemic attack (TIA) ≤ 6 months prior to Day 1
Participant has myelodysplastic syndrome/acute myeloid leukemia or with features
suggestive of MDS/AML
Participant has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea)
Prior therapy with PARP inhibitors at a therapeutic dose
Treatment with another investigational drug or other intervention within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer
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