A Study Assessing Pamiparib With Radiation and / or Temozolomide (TMZ) in Subjects With Newly Diagnosed or Recurrent Glioblastoma

Status: Active

Description

This study is to evaluate the safety, efficacy and clinical activity of Pamiparib in combination with radiation therapy (RT) and / or temozolomide (TMZ) in subjects with newly diagnosed or recurrent / refractory glioblastoma.

Eligibility Criteria

Inclusion Criteria

  • Inclusion Criteria: All subjects 1. Age ≥ 18 years old. 2. Confirmed diagnosis of glioblastoma (WHO Grade IV). 3. Agreement to provide archival tumor tissue for exploratory biomarker analysis 4. Ability to undergo serial MRIs. 5. ECOG status ≤ 1. 6. Adequate hematologic and end-organ function 7. Females of childbearing potential and non-sterile males must agree to use highly effective methods of birth control throughout the course of study and at least up to 6 months after last dosing. 8. Ability to swallow whole capsules. Subjects in Arms A and B (not Arm C) must meet inclusion criteria # 9 - 11: 9. No previous treatment for GBM except surgery. 10. Able to start radiation therapy ≤ 49 days after surgery but ≥ 14 days after a biopsy or ≥28 days after an open biopsy or craniotomy with adequate wound healing. 11. Documented unmethylated MGMT promoter status. Subjects in Arm C Escalation (Phase 1b) must meet inclusion criteria # 12 - 15: 12. Documentation of MGMT promoter status 13. No prior systemic chemotherapy other than TMZ for GBM. 14. Histologically confirmed secondary glioblastoma 15. Disease that is evaluable or measurable as defined by RANO criteria Subjects in Arm C Expansion (Phase 2), must meet criteria # 16 - 18: 16. Histologically confirmed de novo (primary) glioblastoma with unequivocal first progressive disease (PD) after RT with concurrent/adjuvant TMZ chemotherapy 17. Disease that is measurable as defined by RANO criteria 18. Documentation of MGMT promoter status Exclusion Criteria: All subjects 1. Prior chemotherapy, biologic therapy, immunotherapy or investigational agents ≤21 days prior to start of study treatment. 2. Toxicity of ≥ Grade 2 from prior therapy. 3. Major surgery or significant other injury ≤ 4 weeks prior to start of study treatment. 4. History of other active malignancies within 2 years with exception of (i) adequately treated in situ cancer of the cervix, (ii) non-melanoma skin cancer, or (iii) localized adequately treated cancer with curative intent or malignancy diagnosed > 2 years ago with no evidence of disease and no treatment ≤ 2 years prior to study treatment. 5. Active infection requiring systemic treatment. 6. Known human immunodeficiency virus (HIV) or active viral hepatitis. 7. Active, clinically significant cardiac disease or any Class 3 or 4 cardiac disease, ventricular arrhythmia or CVA ≤ 6 months prior to start of treatment. 8. Active clinically significant gastrointestinal disease. 9. Active bleeding disorder ≤ 6 months prior to start of treatment. 10. Need for therapeutic anti-coagulation with heparin, warfarin or other anticoagulants. 11. Use of any medications or food known to be strong or moderate cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or strong inducers. 12. Pregnant or nursing females. 13. Significant intercurrent illness that may result in subject's death prior to death from glioblastoma. Arms B and C Only: 14. Known hypersensitivity to any component of TMZ or decarbazine (DTIC). 15. Have hereditary problems of galactose intolerance

Locations & Contacts

California

Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: Active
Contact: Li Quan
Phone: 310-825-1416
Email: quanli@mednet.ucla.edu
San Francisco
UCSF Medical Center-Mount Zion
Status: Active
Name Not Available

Massachusetts

Boston
Brigham and Women's Hospital
Status: Active
Name Not Available
Dana-Farber Cancer Institute
Status: Active
Name Not Available
Massachusetts General Hospital Cancer Center
Status: Active
Name Not Available

New York

New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Anna Paula Feliciano Piotrowski
Phone: 212-610-0483
Email: piotrowa@mskcc.org
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: Active
Name Not Available

Ohio

Cleveland
Case Comprehensive Cancer Center
Status: Active
Name Not Available
Columbus
Ohio State University Comprehensive Cancer Center
Status: Active
Name Not Available

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: Active
Name Not Available

Pennsylvania

Philadelphia
Thomas Jefferson University Hospital
Status: Active
Name Not Available

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: Active
Name Not Available

Virginia

Charlottesville
University of Virginia Cancer Center
Status: Active
Name Not Available

Trial Objectives and Outline

An open‑label, multiple‑dose, dose-escalation study to determine the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of Pamiparib in combination with radiation therapy (RT) and/or TMZ. In dose escalation/Phase 1b, Pamiparib will be combined with RT (Arm A) or RT and TMZ (Arm B) in subjects with newly diagnosed unmethylated glioblastoma (GBM) and in Arm C of the study Pamiparib will be combined with TMZ in subjects with methylated or unmethylated recurrent/refractory GBM. The dose expansion/Phase 2 phase will enroll up to 4 cohorts: subjects with newly diagnosed unmethylated GBM in Arms A and B, and 2 cohorts of subjects with recurrent/refractory GBM grouped by MGMT status - unmethylated or methylated - in Arm C. Subjects in Arms A and B are treated until completion of RT and subjects in Arm C may continue treatment in the absence of safety concerns and disease progression.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
BeiGene USA, Inc.

Trial IDs

Primary ID BGB-290-104
Secondary IDs NCI-2017-01307
Clinicaltrials.gov ID NCT03150862