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

NCT03150862 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: BGB-290-1042017-001554-33
• Study Type: interventional
• Target: 116
• Locations: 5 countries
• Sites: 22

Brief 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.

Conditions

Brain and Central Nervous System Tumors

Keywords

Adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma, glioma neoplasms; recurrent adult brain tumor; neoplasms, central nervous system neoplasms, neoplasms by histologic type, neoplasms by site; astrocytoma; neuroepithelial; neuroectodermal tumors; germ cell and embryonal; antineoplastic agents; glandular and epithelial; nerve tissue, nervous system diseases; temozolomide; BGB-290; alkylating, alkylating agents; molecular mechanisms of pharmacological action; Poly(ADP-ribose) polymerase inhibitors; enzyme inhibitors

Outcome Measures

Primary Outcomes (7)

• Phase 1b Escalation Phase: Number of Participants With Dose-Limiting Toxicities (DLTs) as Assessed by CTCAE

  A DLT is defined as one of the following toxicities occurring during the DLT assessment window: Grade ≥3 non-hematologic, non-hepatic major organ adverse event (AE) Grade 4 neutropenia lasting \>7 days Grade ≥3 febrile neutropenia Grade 3 thrombocytopenia with clinically significant bleeding Grade 4 thrombocytopenia lasting \> 3 days and requiring transfusion, or any decreased platelet count \<15,000/mm3/ \<15.0 x 109/L Grade ≥4 anemia Grade ≥3 total bilirubin or hepatic transaminases (ALT or AST)

  Arm A:Day 1 Pamiparib dose until 4 weeks after the last RT; Arm B: Day 1 of Pamiparib and Temozolomide until 4 weeks after the last RT; Arm C: 1st cycle of 28 days

• Phase 1b Escalation Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as Assessed by CTCAE

  A treatment-emergent adverse event (TEAE) is defined as an AE that had an onset date on or after first dose of study treatment or was worsening in severity from baseline (pretreatment) up to 30 days following permanent study treatment discontinuation or initiation of new anti-cancer therapy, whichever occurs first. An SAE is any untoward medical occurrence that, at any dose meets at least one of the following criteria: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is considered a significant medical AE based on medical judgment.

  From initiation of study treatment (for TEAE) or from the date informed consent has been signed (for SAE), until 30 days after last study treatment or initiation of new anticancer therapy, whichever occurs first (up to 3 years and 7.5 months)

• Phase 1b Escalation Phase Arm C: Number of Participants With Clinically Relevant Changes in Vital Signs and Clinical Laboratory Measurements

  From the date of first dose up to end of study (EOS) visit (up to 3 years and 7.5 months)

• Phase 2 Arm A: Modified Disease Control Rate (DCR) as Assessed by Response Assessment in Neuro-Oncology (RANO) Criteria

  Modified DCR is defined as the percentage of participants with complete response (CR), partial response (PR) or stable disease (SD) per RANO criteria as the response assessment at the end-of-treatment (EOT) visit.

  From the date of first dose up to first documentation of disease progression while participant is alive ( up to 3 years and 7.5 months)

• Phase 2 Arm C: Objective Response Rate (ORR) as Assessed Using RANO Criteria

  ORR (objective response rate) is defined as percentage of participants with best overall response of CR or PR per RANO criteria (confirmed by a subsequent tumor assessment at least four weeks apart).

  From the date of first dose up to first documentation of disease progression while participant is alive (up to 3 years and 7.5 months)

• Phase 1b Arm C: Number of Cycles of Treatment Received by Participants

  Data shows the number of participants who received treatment for the given number of cycles.

  From the date of first dose up to EOS visit ( up to 3 years and 7.5 months)

• Phase 1b Arm C: Average Dose Intensity of Pamiparib And TMZ Received Per Participant

  The average dose intensity per participant = total dose (mg) per participant / duration of treatment (days).

  From the date of first dose until EOS visit (up to 3 years and 7.5 months)

Secondary Outcomes (12)

• Phase 1B and Phase 2: Pharmacokinetics: Ctrough of Pamiparib

  Pre-dose, 2 hours post dose on Days 1 and 15 of radiation Therapy

• Phase 1b Arm A and Arm B Escalation Phase: Modified Disease Control Rate as Assessed by RANO Criteria

  From the date of first dose up to first documentation of disease progression while participant is alive (approximately 3 years and 7.5 months)

• Phase 1b Escalation Phase Arm C: Disease Control Rate as Assessed by RANO Criteria

  From the date of first dose up to first documentation of disease progression while participant is alive (up to 3 years and 7.5 months)

• Phase 1b and Phase 2 Arms A and B: ORR as Assessed Using RANO Criteria

  From the date of first dose up to first documentation of disease progression while participant is alive ( up to 3 years and 7.5 months)

• Phase 1b and Phase 2 Arms A, B and C: Clinical Benefit Rate as Assessed Using RANO Criteria

  From the date of first dose up to first documentation of disease progression while participant is alive (up to 3 years and 7.5 months)

Study Arms (5)

Arm A (Dose Escalation)

EXPERIMENTAL

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

Drug: Pamiparib; Radiation: Radiation

Arm B (Dose Escalation)

EXPERIMENTAL

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

Drug: Pamiparib; Drug: TMZ; Radiation: Radiation

Arm A (Dose Expansion)

EXPERIMENTAL

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

Drug: Pamiparib; Radiation: Radiation

Arm C (Dose Escalation)

EXPERIMENTAL

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

Drug: Pamiparib; Drug: TMZ

Arm C (Dose Expansion-Cohorts C1 and C2)

EXPERIMENTAL

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

Drug: Pamiparib; Drug: TMZ

Interventions

Pamiparib DRUG

Administered as specified in the treatment arm

Also known as: BGB-290

Arm A (Dose Escalation); Arm A (Dose Expansion); Arm B (Dose Escalation); Arm C (Dose Escalation); Arm C (Dose Expansion-Cohorts C1 and C2)

TMZ DRUG

Administered as specified in the treatment arm

Arm B (Dose Escalation); Arm C (Dose Escalation); Arm C (Dose Expansion-Cohorts C1 and C2)

Radiation RADIATION

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

Arm A (Dose Escalation); Arm A (Dose Expansion); Arm B (Dose Escalation)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years old.
• Confirmed diagnosis of glioblastoma (WHO Grade IV).
• Agreement to provide archival tumor tissue for exploratory biomarker analysis
• Ability to undergo serial MRIs.
• Eastern Cooperative Oncology Group (ECOG) status ≤ 1.
• Adequate hematologic and end-organ function
• 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.
• Ability to swallow whole capsules.
• No previous treatment for GBM except surgery.
• 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.
• Documented unmethylated MGMT promoter status.
• Documentation of MGMT promoter status
• No prior systemic chemotherapy other than TMZ for GBM.
• Histologically confirmed secondary glioblastoma
• Disease that is evaluable or measurable as defined by Response Assessment in Neuro-Oncology (RANO) criteria

You may not qualify if:

• Prior chemotherapy, biologic therapy, immunotherapy or investigational agents ≤21 days prior to start of study treatment.
• Toxicity of ≥ Grade 2 from prior therapy.
• Major surgery or significant other injury ≤ 4 weeks prior to start of study treatment.
• 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.
• Active infection requiring systemic treatment.
• Known human immunodeficiency virus (HIV) or active viral hepatitis.
• 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.
• Active clinically significant gastrointestinal disease.
• Active bleeding disorder ≤ 6 months prior to start of treatment.
• Need for therapeutic anti-coagulation with heparin, warfarin or other anticoagulants.
• Use of any medications or food known to be strong or moderate cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or strong inducers.
• Pregnant or nursing females.
• Significant intercurrent illness that may result in participant's death prior to death from glioblastoma.
• Arms B and C Only:
• Known hypersensitivity to any component of TMZ or decarbazine (DTIC).

Sponsors & Collaborators

• BeiGene USA, Inc.: lead

Study Sites (22)

Center For Neurosciences

Tucson, Arizona, 85718, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

University of California At San Francisco

San Francisco, California, 94143, United States

Location

Sarah Cannon Research Institute (Scri) At Health One

Denver, Colorado, 80219, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Midamerica Division, Inc

Kansas City, Missouri, 64132, United States

Location

Washington University in St Louis

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center Mskcc

New York, New York, 10065, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Sarah Cannon Research Institute (Scri) Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Thomas Jefferson University Hospital Jefferson Health

Philadelphia, Pennsylvania, 19107, United States

Location

Tennessee Oncology, Pllc Nashville

Nashville, Tennessee, 37203, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Universitair Medisch Centrum Utrecht

Utrecht, 3584 CX, Netherlands

Location

University of Zurich Medical School

Zurich, 8032, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 32652442 DERIVED

MeSH Terms

Conditions

Central Nervous System Neoplasms; Glioblastoma; Gliosarcoma; Brain Neoplasms; Neoplasms; Neoplasms by Histologic Type; Neoplasms by Site; Astrocytoma; Neuroectodermal Tumors; Nervous System Diseases

Interventions

pamiparib; Radiation

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Glioma; Neoplasms, Neuroepithelial; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Physical Phenomena

Results Point of Contact

• Title: Study Director
• Organization: BeiGene

clinicaltrials@beigene.com

+1-877-828-5568

Study Officials

• Study Director

  BeiGene

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: No Masking
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2017
• First Posted: May 12, 2017
• Study Start: July 24, 2017
• Primary Completion: March 17, 2021
• Study Completion: March 17, 2021
• Last Updated: February 4, 2025
• Results First Posted: May 31, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share

Locations

CH (1); AU (1); US (18); FR (1); NL (1)