PARP Inhibition for Gliomas (PI-4G or π4g) (OU-SCC-PI-4G)

Phase II Trial of Niraparib in Patients With Recurrent Glioma

The purpose of this study is to determine what effects (good and bad) niraparib has on patients with recurrent brain cancer.

Study Overview

• Status: Terminated
• Conditions: Recurrent Glioblastoma; Recurrent Glioma; Recurrent Astrocytoma; Recurrent Oligodendroglioma
• Intervention / Treatment: Drug: Niraparib

Detailed Description

Patients will have tests and exams to see if they are eligible for the clinical trial. If found eligible, the patient will receive treatment with niraparib in the form of capsules taken every day for the first 28 days. If this dose is tolerated well, the patients will continue to take the capsules and more patients will be enrolled on the study.

Patients will continue treatment with niraparib while on the study unless there is evidence of tumor growth or they experience unacceptable side effects.

Patients will be monitored during treatment with tests and exams and after treatment completion for up to four years from the time they enrolled on the study.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Stephenson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients must be able to understand and willing to sign the informed consent form.
2. Patients must be ≥ 18 years of age.
3. Patients must have histologically proven high grade gliomas - GBM, Astrocytoma, or Oligodendroglioma (glioma WHO Grade III or IV) that is now recurrent by MRI or surgical pathology.
4. Patients must have measurable or evaluable lesions by RANO.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
6. Patient has archival tumor tissue available; or a fresh biopsy of recurrent or persistent tumor must be obtained for molecular assay by myChoice test (Myriad Genetics) prior to study treatment initiation. Patient will be requested to share reports from any prior genetic testing with the study investigators.
7. Participants have systolic BP< 140 mmHg or diastolic BP <90 mmHg that has been adequately treated or controlled.
8. Have adequate organ function defined per protocol.
9. Be able to take oral medications
10. Life expectancy ≥ 3 months, allowing adequate follow up of toxicity evaluation and antitumor activity;
11. Female patient, if of childbearing potential, has a negative serum pregnancy test within 72 hours of taking study medication and agrees to abstain from activities that could result in pregnancy from enrollment through 180 days after the last dose of study treatment or is of nonchildbearing potential.
12. Male participant agrees to use an adequate method of contraception starting with the first dose of study treatment through 180 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient. In addition, men must not donate sperm during niraparib therapy and for 90 days after receiving the last dose of niraparib.
13. Patient must agree to not breastfeed during the study or for 30 days after the last dose of study treatment.
14. Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
15. Participant receiving corticosteroids may continue as long as their dose is stable for at least 4 weeks prior to initiating protocol therapy.

Exclusion Criteria:

1. Patient has a known additional malignancy that progressed or required active treatment within the last 3 years (exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer).
2. Prior treatment with a known poly(ADP-ribose) polymerase (PARP) inhibitor
3. Participants with human immunodeficiency virus (HIV) with detectable viral load. Participants with HIV on effective anti-retroviral therapy with documented undetectable viral load and CD4 count ≥ 350 within 6 months of the first dose of study treatment are eligible for this trial.
4. Known active hepatitis B or hepatitis C.
5. Known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
6. Participant is pregnant or expecting to conceive while receiving study treatment and/or for up to 180 days after the last dose of study treatment.Patient currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior to the first dose of study drug.
7. Received prior anticancer therapy (chemotherapy, targeted therapies, radiotherapy, or immunotherapy) within 4 weeks
8. Patients must not have a known hypersensitivity to the components of niraparib or the excipients (lactose monohydrate and magnesium stearate).
9. Patients must not have had major surgery within 4 weeks (including craniotomy) of starting the study and patient must have recovered from any effects of any major surgery. Stereotactic biopsy by burr hole is considered a minor surgery, and those patients undergoing this surgery will be eligible for the study 2 weeks post-procedure.
10. Patients must not have had radiotherapy encompassing > 20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy.
11. Patients must not have received a transfusion (platelets or red blood cells), colony stimulating factors (eg, granulocyte colony-stimulating factor, granulocyte macrophage colony stimulating factor, or recombinant erythropoietin) ≤ 4 weeks of the first dose of study treatment.
12. Patient 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.
13. Participants have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels.
14. Participants have received live vaccine within 30 days of planned start of study randomization.
15. Patients have medical risk due to 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
16. Any medical condition not yet specified above that is considered to possibly, probably or definitely interfere with study procedures, including adequate follow-up and compliance and/or would jeopardize safe treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Niraparib Treatment; Patients will be treated with individualized starting dose of Niraparib.	Drug: Niraparib; The starting dose will be 300 mg niraparib (or modified according patient weight and platelet count), taken orally once a day for each cycle of 28 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients who experience toxicities with individualized starting dose (ISD) of niraparib using CTCAE v5.0. [Safety and Tolerability of niraparib] in safety-lead in phase	Number of patients who experience toxicities with individualized starting dose (ISD) of niraparib using CTCAE v5.0	Up to 4 years
Efficacy of treatment in Dose expansion phase	Percentage of patients who respond to niraparib monitored by disease control rate (stable disease and better) using RANO from start of treatment for up to 12 months.	up to 12 months
Number of patients who experience toxicities with individualized starting dose (ISD) of niraparib using CTCAE v5.0 [Safety of niraparib] in dose expansion phase	Number of patients who experience toxicities with individualized starting dose (ISD) of niraparib using CTCAE v5.0	up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival in Dose expansion phase	Proportion of patients who have progression-free survival from date of study entry until the first documented date of progression or date of death, whichever comes first.	up to 4 years
Overall survival in Dose expansion phase	Proportion of patients with overall survival on the study defined as time from date of study entry to death by any cause.	up to 4 years
Duration of disease control of all patients	Duration of response in patients treated with niraparib defined as time from date of first response (stable disease or better) to the first date of non-response post treatment on the study.	up to 4 years

Collaborators and Investigators

• Sponsor: University of Oklahoma
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: James Battiste, MD, Stephenson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2022
• Primary Completion (Actual): November 14, 2023
• Study Completion (Actual): February 6, 2024

Study Registration Dates

• First Submitted: March 9, 2022
• First Submitted That Met QC Criteria: March 25, 2022
• First Posted (Actual): March 28, 2022

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: high grade gliomas
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Recurrence; Glioma; Astrocytoma; Oligodendroglioma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Niraparib
• Other Study ID Numbers: OU-SCC-PI-4G

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes