Brain and Central Nervous System TumorsPhase 1/2NCT03150862
A Study Assessing Pamiparib With Radiation and/or Temozolomide (TMZ) in Participants With Newly Diagnosed or Recurrent Glioblastoma
A Phase 1/2 study testing Pamiparib, TMZ and Radiation in people with Brain and Central Nervous System Tumors, run by BeiGene USA, Inc. at 22 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain and Central Nervous System Tumors
- What is being tested?
- Pamiparib, TMZ and Radiation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 116 participants
- Where
- 22 sitesin 5 countries
- Study dates
- 24 Jul 2017to 17 Mar 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
22 sites in 5 countries.
22 sites in 5 countries
United States18 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
University of Virginia
Charlottesville, Virginia, 22903
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Ohio State University
Columbus, Ohio, 43210
Sarah Cannon Research Institute (Scri) At Health One
Denver, Colorado, 80219
Henry Ford Hospital
Detroit, Michigan, 48202
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033
Midamerica Division, Inc
Kansas City, Missouri, 64132
UCLA
Los Angeles, California, 90095
Tennessee Oncology, Pllc Nashville
Nashville, Tennessee, 37203
Memorial Sloan Kettering Cancer Center Mskcc
New York, New York, 10065
Sarah Cannon Research Institute (Scri) Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Thomas Jefferson University Hospital Jefferson Health
Philadelphia, Pennsylvania, 19107
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
University of California At San Francisco
San Francisco, California, 94143
Washington University in St Louis
St Louis, Missouri, 63110
Center For Neurosciences
Tucson, Arizona, 85718
About this study
Official title: 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
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.
Read the 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.
- Conditions
- Brain and Central Nervous System Tumors
- Being tested
- Pamiparib, TMZ, Radiation
- 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
- Medical subject headings
- Central Nervous System Neoplasms, Glioblastoma, Gliosarcoma, Brain Neoplasms, Neoplasms, Neoplasms by Histologic Type, Neoplasms by Site, Astrocytoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PamiparibDrug
Also called BGB-290
Administered as specified in the treatment arm
TMZDrug
Administered as specified in the treatment arm
RadiationRadiation
Up to 60 Gy (total) over 6 - 7 weeks
| Study group | Role | What they receive |
|---|---|---|
| Arm A (Dose Escalation) | Experimental | Participants with newly diagnosed unmethylated GBM will receive Pamiparib and radiation therapy. Receives: Drug: Pamiparib; Radiation: Radiation |
| Arm B (Dose Escalation) | Experimental | Participants with newly diagnosed unmethylated GBM will receive Pamiparib, radiation therapy (RT) and temozolomide (TMZ). Receives: Drug: Pamiparib; Drug: TMZ; Radiation: Radiation |
| Arm A (Dose Expansion) | Experimental | Participants with newly diagnosed unmethylated GBM will receive Pamiparib and radiation therapy. Receives: Drug: Pamiparib; Radiation: Radiation |
| Arm C (Dose Escalation) | Experimental | Participants with recurrent/refractory methylated or unmethylated GBM will receive Pamiparib and TMZ. Receives: 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. Receives: Drug: Pamiparib; Drug: TMZ |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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
Measured: 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
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.
Measured: 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
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
Measured: 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
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).
Measured: 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
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).
Measured: 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: Duration of Response (DOR) as Assessed Using RANO Criteria
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).
Measured: From first documentation of CR or PR to first documentation of disease progression or death (up to 3 years and 7.5 months)
Phase 1b and Phase 2 Arms A, B and C: Progression Free Survival (PFS) as Assessed Using RANO Criteria
PFS is defined as the time from the first dose date to disease progression per RANO criteria or death, whichever occurs first.
Measured: From the date of first dose up to first documentation of disease progression or death (up to 3 years and 7.5 months)
Phase 1b and Phase 2 Arms A, B and C: Overall Survival (OS)
OS is defined as the time from the first dose date to date of death for any cause.
Measured: From the date of first dose up to the date of death (up to 3 years and 7.5 months)
Phase 2 Arms A and C Expansion Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
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.
Measured: 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 2 Expansion Phase Arm A and C: Number of Participants With Clinically Relevant Changes in Vital Signs and Clinical Laboratory Measurements
Measured: From the date of first dose up to EOS visit (up to 3 years and 7.5 months)
Phase 2 Arms A and C Expansion Phase: Number of Cycles of Treatment Received by Participants
Data shows the number of participants who received treatment for the given number of cycles.
Measured: From date of first dose up to EOS Visit (up to 3 years and 7.5 months)
Phase 2 Arms A and C Expansion Phase: 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).
Measured: From date of first dose up to EOS Visit (up to 3 years and 7.5 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2017
- Study start24 Jul 2017
- Primary completion17 Mar 2021
- Study completion17 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 116 participants (actual)
Sponsor and investigators
- Lead sponsor
- BeiGene USA, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, BeiGene
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03150862
- Sponsor's protocol ID
- BGB-290-104
- Other IDs
- 2017-001554-33, 2017
- Status last verified
- May 2022
- First submitted
- 8 May 2017
- Last updated
- 4 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
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.
PubMed 32652442
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03150862
- Acronym / sponsor ID
- BGB-290-104
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 116 participants (actual)
- Lead sponsor
- BeiGene USA, Inc.Industry (pharma, biotech, devices)
- Study start
- 24 Jul 2017 (actual)
- Primary completion
- 17 Mar 2021 (actual)
- Study completion
- 17 Mar 2021 (actual)
- First posted
- 12 May 2017 (actual)
- Results
- Posted 31 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Arm A (Dose Escalation) | Experimental | Drug: Pamiparib, Radiation: RadiationParticipants with newly diagnosed unmethylated GBM will receive Pamiparib and radiation therapy. |
| Arm B (Dose Escalation) | Experimental | Drug: Pamiparib, Drug: TMZ, Radiation: RadiationParticipants with newly diagnosed unmethylated GBM will receive Pamiparib, radiation therapy (RT) and temozolomide (TMZ). |
| Arm A (Dose Expansion) | Experimental | Drug: Pamiparib, Radiation: RadiationParticipants with newly diagnosed unmethylated GBM will receive Pamiparib and radiation therapy. |
| Arm C (Dose Escalation) | Experimental | Drug: Pamiparib, Drug: TMZParticipants with recurrent/refractory methylated or unmethylated GBM will receive Pamiparib and TMZ. |
| Arm C (Dose Expansion-Cohorts C1 and C2) | Experimental | Drug: Pamiparib, Drug: TMZParticipants with recurrent/refractory methylated or unmethylated GBM will receive Pamiparib and TMZ. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PamiparibAlso: BGB-290Administered as specified in the treatment arm | Drug | Arm A (Dose Escalation), Arm A (Dose Expansion), Arm B (Dose Escalation), Arm C (Dose Escalation), Arm C (Dose Expansion-Cohorts C1 and C2) |
| TMZAdministered as specified in the treatment arm | Drug | Arm B (Dose Escalation), Arm C (Dose Escalation), Arm C (Dose Expansion-Cohorts C1 and C2) |
| RadiationUp to 60 Gy (total) over 6 - 7 weeks | Radiation | Arm A (Dose Escalation), Arm A (Dose Expansion), Arm B (Dose Escalation) |
Primary outcome
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
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)
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)
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.
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)
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)
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.
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)
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).
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)
Data shows the number of participants who received treatment for the given number of cycles.
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)
The average dose intensity per participant = total dose (mg) per participant / duration of treatment (days).
12 secondary outcomes
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
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32652442Xiong 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.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
BeiGene
22 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pamiparib, TMZ and Radiation in people with Brain and Central Nervous System Tumors, run by BeiGene USA, Inc. at 22 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States, Australia, France, Netherlands, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03150862, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2025; AzTrials last refreshed its copy on 1 Nov 2026.