- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03150862
A Study Assessing Pamiparib With Radiation and/or Temozolomide (TMZ) in Participants With Newly Diagnosed or Recurrent Glioblastoma
A Phase 1b/2 Study to Assess the Safety, Tolerability and Efficacy of BGB-290 in Combination With Radiation Therapy (RT) and/or Temozolomide (TMZ) in Subjects With First-line or Recurrent/Refractory Glioblastoma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Rotterdam, Netherlands, 3015 GD
- Erasmus University Medical Center
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Zurich, Switzerland, CH-8091
- Universitätsspital Zuerich - Klinik fur Neurologie
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Arizona
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Tucson, Arizona, United States, 85718
- Center for Neurosciences
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California
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Los Angeles, California, United States, 90095
- UCLA Neuro-Oncology
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San Francisco, California, United States, 94143
- University of California at San Francisco
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Colorado
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Denver, Colorado, United States, 80218
- Sarah Cannon Research Institute at Health One
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Dana Farber Cancer Institute
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Boston, Massachusetts, United States, 02214
- Massachusetts General Hospital Pappas Center for Neuro-Oncology
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Michigan
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Detroit, Michigan, United States, 48202
- Henry Ford Health Systems
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Missouri
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Kansas City, Missouri, United States, 64132
- Health Midwest Ventures Group, LLC
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Saint Louis, Missouri, United States, 63110
- Washington University
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New York
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New York, New York, United States, 10065
- Memorial Sloan Kettering Cancer Center
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Ohio
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Cleveland, Ohio, United States, 44195
- Cleveland Clinic
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Columbus, Ohio, United States, 43210
- The Ohio State University
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Oklahoma
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Oklahoma City, Oklahoma, United States, 73104
- University of Oklahoma Health Sciences Center (Stephenson Cancer Center)
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Pennsylvania
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Hershey, Pennsylvania, United States, 17033
- Penn State Milton S Hershey Medical Center
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Philadelphia, Pennsylvania, United States, 19107
- Thomas Jefferson University
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Tennessee
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Nashville, Tennessee, United States, 37203
- SCRI / Tennessee Oncology
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Utah
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Salt Lake City, Utah, United States, 84112
- Huntsman Cancer Center
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Virginia
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Charlottesville, Virginia, United States, 22903
- University of Virginia Health Systems
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Key Inclusion Criteria: All participants
- 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.
Participants in Arms A and B (not Arm C) must meet inclusion criteria # 9 - 11:
- 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.
Participants in Arm C Escalation (Phase 1b) must meet inclusion criteria # 12 - 15:
- 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
Participants in Arm C Expansion (Phase 2), must meet criteria # 16 - 18:
- Histologically confirmed de novo (primary) glioblastoma with unequivocal first progressive disease (PD) after RT with concurrent/adjuvant TMZ chemotherapy
- Disease that is measurable as defined by RANO criteria
- Documentation of MGMT promoter status
Key Exclusion Criteria: All participants
- 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).
- Have hereditary problems of galactose intolerance
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Arm A (Dose Escalation)
Participants with newly diagnosed unmethylated GBM will receive Pamiparib and radiation therapy.
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Administered as specified in the treatment arm
Other Names:
Up to 60 Gy (total) over 6 - 7 weeks
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Experimental: Arm B (Dose Escalation)
Participants with newly diagnosed unmethylated GBM will receive Pamiparib, radiation therapy (RT) and temozolomide (TMZ).
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Administered as specified in the treatment arm
Other Names:
Up to 60 Gy (total) over 6 - 7 weeks
Administered as specified in the treatment arm
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Experimental: Arm A (Dose Expansion)
Participants with newly diagnosed unmethylated GBM will receive Pamiparib and radiation therapy.
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Administered as specified in the treatment arm
Other Names:
Up to 60 Gy (total) over 6 - 7 weeks
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Experimental: Arm C (Dose Escalation)
Participants with recurrent/refractory methylated or unmethylated GBM will receive Pamiparib and TMZ.
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Administered as specified in the treatment arm
Other Names:
Administered as specified in the treatment arm
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Experimental: Arm C (Dose Expansion-Cohorts C1 and C2)
Participants with recurrent/refractory methylated or unmethylated GBM will receive Pamiparib and TMZ.
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Administered as specified in the treatment arm
Other Names:
Administered as specified in the treatment arm
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Phase 1b Escalation Phase: Number of Participants With Dose-Limiting Toxicities (DLTs) as Assessed by CTCAE
Time Frame: 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
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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
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Phase 1b Escalation Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as Assessed by CTCAE
Time Frame: 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)
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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)
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Phase 1b Escalation Phase Arm C: Number of Participants With Clinically Relevant Changes in Vital Signs and Clinical Laboratory Measurements
Time Frame: From the date of first dose up to end of study (EOS) visit (up to 3 years and 7.5 months)
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From the date of first dose up to end of study (EOS) visit (up to 3 years and 7.5 months)
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Phase 2 Arm A: Modified Disease Control Rate (DCR) as Assessed by Response Assessment in Neuro-Oncology (RANO) Criteria
Time Frame: 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)
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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.
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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)
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Phase 2 Arm C: Objective Response Rate (ORR) as Assessed Using RANO Criteria
Time Frame: 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)
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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).
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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)
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Phase 1b Arm C: Number of Cycles of Treatment Received by Participants
Time Frame: From the date of first dose up to EOS visit ( up to 3 years and 7.5 months)
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Data shows the number of participants who received treatment for the given number of cycles.
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From the date of first dose up to EOS visit ( up to 3 years and 7.5 months)
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Phase 1b Arm C: Average Dose Intensity of Pamiparib And TMZ Received Per Participant
Time Frame: From the date of first dose until EOS visit (up to 3 years and 7.5 months)
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The average dose intensity per participant = total dose (mg) per participant / duration of treatment (days).
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From the date of first dose until EOS visit (up to 3 years and 7.5 months)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Phase 1B and Phase 2: Pharmacokinetics: Ctrough of Pamiparib
Time Frame: Pre-dose, 2 hours post dose on Days 1 and 15 of radiation Therapy
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Pre-dose, 2 hours post dose on Days 1 and 15 of radiation Therapy
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Phase 1b Arm A and Arm B Escalation Phase: Modified Disease Control Rate as Assessed by RANO Criteria
Time Frame: From the date of first dose up to first documentation of disease progression while participant is alive (approximately 3 years and 7.5 months)
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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.
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From the date of first dose up to first documentation of disease progression while participant is alive (approximately 3 years and 7.5 months)
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Phase 1b Escalation Phase Arm C: Disease Control Rate as Assessed by RANO Criteria
Time Frame: 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)
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DCR is defined as the percentage of participants with best overall response of CR, PR or SD per RANO criteria.
CR or PR will be confirmed by a subsequent tumor assessment at least four weeks apart
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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)
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Phase 1b and Phase 2 Arms A and B: ORR as Assessed Using RANO Criteria
Time Frame: 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)
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ORR 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).
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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)
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Phase 1b and Phase 2 Arms A, B and C: Clinical Benefit Rate as Assessed Using RANO Criteria
Time Frame: 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)
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Clinical benefit rate (CBR) is defined as the percentage of participants with best overall response of CR, PR or SD ≥ 24 weeks per RANO criteria (confirmed by a subsequent tumor assessment at least four weeks apart).
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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)
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Phase 1b and Phase 2 Arms A, B and C: Duration of Response (DOR) as Assessed Using RANO Criteria
Time Frame: From first documentation of CR or PR to first documentation of disease progression or death (up to 3 years and 7.5 months)
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DOR is defined as the time from the date of the earliest documented response to disease progression or death for any cause whichever occurs earlier (confirmed by a subsequent tumor assessment at least four weeks apart).
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From first documentation of CR or PR to first documentation of disease progression or death (up to 3 years and 7.5 months)
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Phase 1b and Phase 2 Arms A, B and C: Progression Free Survival (PFS) as Assessed Using RANO Criteria
Time Frame: From the date of first dose up to first documentation of disease progression or death (up to 3 years and 7.5 months)
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PFS is defined as the time from the first dose date to disease progression per RANO criteria or death, whichever occurs first.
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From the date of first dose up to first documentation of disease progression or death (up to 3 years and 7.5 months)
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Phase 1b and Phase 2 Arms A, B and C: Overall Survival (OS)
Time Frame: From the date of first dose up to the date of death (up to 3 years and 7.5 months)
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OS is defined as the time from the first dose date to date of death for any cause.
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From the date of first dose up to the date of death (up to 3 years and 7.5 months)
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Phase 2 Arms A and C Expansion Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: 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)
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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.
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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)
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Phase 2 Expansion Phase Arm A and C: Number of Participants With Clinically Relevant Changes in Vital Signs and Clinical Laboratory Measurements
Time Frame: From the date of first dose up to EOS visit (up to 3 years and 7.5 months)
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From the date of first dose up to EOS visit (up to 3 years and 7.5 months)
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Phase 2 Arms A and C Expansion Phase: Number of Cycles of Treatment Received by Participants
Time Frame: From date of first dose up to EOS Visit (up to 3 years and 7.5 months)
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Data shows the number of participants who received treatment for the given number of cycles.
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From date of first dose up to EOS Visit (up to 3 years and 7.5 months)
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Phase 2 Arms A and C Expansion Phase: Average Dose Intensity of Pamiparib and TMZ Received Per Participant
Time Frame: From date of first dose up to EOS Visit (up to 3 years and 7.5 months)
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The average dose intensity per participant = total dose (mg) per participant / duration of treatment (days).
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From date of first dose up to EOS Visit (up to 3 years and 7.5 months)
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Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- recurrent adult brain tumor
- temozolomide
- astrocytoma
- antineoplastic agents
- BGB-290
- enzyme inhibitors
- molecular mechanisms of pharmacological action
- Adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma, glioma neoplasms
- neoplasms, central nervous system neoplasms, neoplasms by histologic type, neoplasms by site
- neuroepithelial
- neuroectodermal tumors
- germ cell and embryonal
- glandular and epithelial
- nerve tissue, nervous system diseases
- alkylating, alkylating agents
- Poly(ADP-ribose) polymerase inhibitors
Additional Relevant MeSH Terms
- Nervous System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Astrocytoma
- Glioma
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Glioblastoma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
Other Study ID Numbers
- BGB-290-104
- 2017-001554-33 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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