Overview
A Study Assessing Pamiparib With Radiation and/or Temozolomide (TMZ) in Participants With Newly Diagnosed or Recurrent Glioblastoma
Status:
Completed
Completed
Trial end date:
2021-03-17
2021-03-17
Target enrollment:
0
0
Participant gender:
All
All
Summary
The primary objective of this study is to evaluate the safety, efficacy and clinical activity of Pamiparib in combination with radiation therapy (RT) and/or temozolomide (TMZ) in participants with newly diagnosed or recurrent/refractory glioblastoma.Phase:
Phase 1/Phase 2Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
BeiGene USA, Inc.Treatments:
Dacarbazine
Molecular Mechanisms of Pharmacological Action
Poly(ADP-ribose) Polymerase Inhibitors
Temozolomide
Criteria
Key Inclusion Criteria: All participants1. 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. Eastern Cooperative Oncology Group (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.
Participants 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.
Participants 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
Participants 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
Key Exclusion Criteria: All participants
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 Cerebrovascular Accident (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 participant'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
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.