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

NCT ID: NCT03150862

Last Updated: 2025-02-04

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

116 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-07-24

Study Completion Date

2021-03-17

Brief Summary

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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.

Detailed Description

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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 participants with newly diagnosed unmethylated glioblastoma (GBM) and in Arm C of the study Pamiparib will be combined with TMZ in participants with methylated or unmethylated recurrent/refractory GBM.

The dose expansion/Phase 2 phase will enroll up to 4 cohorts: participants with newly diagnosed unmethylated GBM in Arms A and B, and 2 cohorts of participants with recurrent/refractory GBM grouped by O-6-methylguanine-DNA methyltransferase (MGMT) status - unmethylated or methylated - in Arm C.

Participants in Arms A and B are treated until completion of RT and participants in Arm C may continue treatment in the absence of safety concerns and disease progression.

Conditions

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Brain and Central Nervous System Tumors

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

No Masking

Study Groups

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Arm A (Dose Escalation)

Participants with newly diagnosed unmethylated GBM will receive Pamiparib and radiation therapy.

Group Type EXPERIMENTAL

Pamiparib

Intervention Type DRUG

Administered as specified in the treatment arm

Radiation

Intervention Type RADIATION

Up to 60 Gy (total) over 6 - 7 weeks

Arm B (Dose Escalation)

Participants with newly diagnosed unmethylated GBM will receive Pamiparib, radiation therapy (RT) and temozolomide (TMZ).

Group Type EXPERIMENTAL

Pamiparib

Intervention Type DRUG

Administered as specified in the treatment arm

TMZ

Intervention Type DRUG

Administered as specified in the treatment arm

Radiation

Intervention Type RADIATION

Up to 60 Gy (total) over 6 - 7 weeks

Arm A (Dose Expansion)

Participants with newly diagnosed unmethylated GBM will receive Pamiparib and radiation therapy.

Group Type EXPERIMENTAL

Pamiparib

Intervention Type DRUG

Administered as specified in the treatment arm

Radiation

Intervention Type RADIATION

Up to 60 Gy (total) over 6 - 7 weeks

Arm C (Dose Escalation)

Participants with recurrent/refractory methylated or unmethylated GBM will receive Pamiparib and TMZ.

Group Type EXPERIMENTAL

Pamiparib

Intervention Type DRUG

Administered as specified in the treatment arm

TMZ

Intervention Type DRUG

Administered as specified in the treatment arm

Arm C (Dose Expansion-Cohorts C1 and C2)

Participants with recurrent/refractory methylated or unmethylated GBM will receive Pamiparib and TMZ.

Group Type EXPERIMENTAL

Pamiparib

Intervention Type DRUG

Administered as specified in the treatment arm

TMZ

Intervention Type DRUG

Administered as specified in the treatment arm

Interventions

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Pamiparib

Administered as specified in the treatment arm

Intervention Type DRUG

TMZ

Administered as specified in the treatment arm

Intervention Type DRUG

Radiation

Up to 60 Gy (total) over 6 - 7 weeks

Intervention Type RADIATION

Other Intervention Names

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BGB-290

Eligibility Criteria

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Inclusion Criteria

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. 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.

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.

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 Response Assessment in Neuro-Oncology (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

Exclusion Criteria

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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BeiGene USA, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Study Director

Role: STUDY_DIRECTOR

BeiGene

Locations

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Center For Neurosciences

Tucson, Arizona, United States

Site Status

UCLA

Los Angeles, California, United States

Site Status

University of California At San Francisco

San Francisco, California, United States

Site Status

Sarah Cannon Research Institute (Scri) At Health One

Denver, Colorado, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Midamerica Division, Inc

Kansas City, Missouri, United States

Site Status

Washington University in St Louis

St Louis, Missouri, United States

Site Status

Memorial Sloan Kettering Cancer Center Mskcc

New York, New York, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Ohio State University

Columbus, Ohio, United States

Site Status

Sarah Cannon Research Institute (Scri) Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Site Status

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Thomas Jefferson University Hospital Jefferson Health

Philadelphia, Pennsylvania, United States

Site Status

Tennessee Oncology, Pllc Nashville

Nashville, Tennessee, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

Liverpool Hospital

Liverpool, New South Wales, Australia

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

Site Status

University of Zurich Medical School

Zurich, , Switzerland

Site Status

Countries

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United States Australia France Netherlands Switzerland

References

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Xiong Y, Guo Y, Liu Y, Wang H, Gong W, Liu Y, Wang X, Gao Y, Yu F, Su D, Wang F, Zhu Y, Zhao Y, Wu Y, Qin Z, Sun X, Ren B, Jiang B, Jin W, Shen Z, Tang Z, Song X, Wang L, Liu X, Zhou C, Jiang B. Pamiparib is a potent and selective PARP inhibitor with unique potential for the treatment of brain tumor. Neoplasia. 2020 Sep;22(9):431-440. doi: 10.1016/j.neo.2020.06.009. Epub 2020 Jul 8.

Reference Type DERIVED
PMID: 32652442 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2017-001554-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BGB-290-104

Identifier Type: -

Identifier Source: org_study_id

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