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GlioblastomaPhase 1PNOC017NCT03749187

BGB-290 and Temozolomide in Treating Isocitrate Dehydrogenase (IDH)1/2-Mutant Grade I-IV Gliomas

A Phase 1 study testing PARP Inhibitor BGB-290 and Temozolomide (TMZ) in people with Glioblastoma and IDH1 Gene Mutation, run by University of California, San Francisco at 11 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This phase I trial studies the side effects and best dose of BGB-290 and temozolomide in treating adolescents and young adults with IDH1/2-mutant grade I-IV glioma that is newly diagnosed or has come back. BGB-290 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 13 to 39 years
What is being tested?
PARP Inhibitor BGB-290 and Temozolomide (TMZ)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
78 participants
Where
11 sitesUnited States
Study dates
3 Apr 2019to 30 Jul 2029
Phase
Phase 1
Are there results?
Not yet: the study is under way

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 13 to 39 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Arm A Only: Participants must have histologically confirmed World Health Organization (WHO) grade III-IV newly diagnosed IDH1/2-mutant glioma.
  • Arm B Only: WHO grades I-IV recurrent IDH1/2 mutant glioma. Participants in Arm B must have magnetic resonance imaging (MRI) confirming progressive disease; re-biopsy is encouraged, but not required at the time of recurrence for confirmation.
  • Participants with a primary spinal tumor, secondary glioma, or multifocal disease in the brain, but without evidence of diffuse leptomeningeal spread, are eligible. In cases where there are questions about multifocality versus diffuse leptomeningeal spread, the study chair or co-chair must be contacted to make a final decision on eligibility.
  • Participants must have IDH1 or IDH2 mutation associated with neomorphic activity of the encoded proteins.
  • Participants must be willing to provide archival formalin-fixed embedded (FFPE) and frozen tissue specimens for biomarker studies if available.
  • Participants in Arm A must have been treated with maximal safe resection of primary tumor followed by adjuvant radiation therapy (RT). Treatment with TMZ during radiation is allowed but not required.
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  • Participants in Arm B must have been treated with maximal safe resection of tumor.
  • Lower grade glioma (LGG) participants who progressed after initial surgery alone are eligible. Any number of prior therapies are allowed.
  • High grade glioma (HGG) participants enrolled on Arm B must have been treated with a minimum of maximal safe resection of primary tumor followed by adjuvant RT prior to recurrence. Any number of prior therapies are allowed.
  • Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
  • Myelosuppressive chemotherapy: participants must have received their last dose of known myelosuppressive anticancer chemotherapy at least three weeks prior to study registration or at least six weeks if nitrosourea.
  • Biologic agent: participants must have recovered from any toxicity related to biologic agents and received their last dose >= 7 days prior to study registration.
  • For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval should be discussed with the study chair.
  • For biologic agents that have a prolonged half-life, the appropriate interval since last treatment should be discussed with the study chair prior to registration.
  • Monoclonal antibody treatment: at least three half-lives must have elapsed prior to registration, and participants on bevacizumab must have received their last dose >= 32 days prior to study registration.
  • Participants in Arm A should begin therapy with TMZ and BGB-290 after completion of radiation therapy and when all other eligibility criteria are met.
  • For participants in Arm B, patients must not have received radiation therapy within 4 weeks prior to the initiation of study treatment. Post-RT, the diagnosis of true progression versus pseudo-progression can be challenging when imaging modalities are exclusively used, and thus an additional resection is encouraged if clinically indicated.
  • Peripheral absolute neutrophil count (ANC) >= 1000/mm^3.
  • Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
  • Hemoglobin >= 9 g/dL.
  • Serum creatinine =< 1.5 x upper limit of normal (ULN) or estimated creatinine clearance >= 50 mL/min (calculated using the institutional standard method).
  • Total serum bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN).
  • Aspartate and alanine aminotransferase (AST and ALT) =< 3 x ULN.
  • Serum albumin >= 2 g/dL.
  • Participants with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlled.
  • Participants who have neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration.
  • Corticosteroids: Participants who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to registration.
  • The effects of BGB-290 on the developing human fetus are unknown. For this reason and because alkylating agents (such as TMZ) are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 4 months after completion of BGB-290 or TMZ administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • Participants must be able to swallow capsules.
  • Participants must have the ability to undergo serial MRI scans (computerized tomography [CT] cannot substitute for MRI).
  • A legal parent/guardian or patient must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.
  • Karnofsky >= 50 for participants > 16 years of age and Lansky >= 50 for participants =< 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.

Who cannot join

  • Participants who are receiving any other investigational agents at any time may not be enrolled.
  • Participants who have received a PARP inhibitor previously.
  • Participants with active infection requiring antibiotics at time of therapy start.
  • Participants with other diagnosis of malignancy.
  • Participants with clinically significant active bleeding disorder, hemoptysis, or melena =< 6 months prior to day 1.
  • Participants on therapeutic anti-coagulation with heparin, warfarin, or other anticoagulants:
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  • Use of low-dose aspirin and/or non-steroidal anti-inflammatory agents are allowed.
  • Use of thrombolytic to establish patency of indwelling venous catheters is allowed.
  • Prophylactic anticoagulation for venous access devices is allowed as long as institutional normalized ratio (INR) is =< 1.5 and partial thromboplastin time (aPTT) =< 1.5 x institutional ULN.
  • Use of low-molecular weight heparin is allowed.
  • Participants with known disseminated leptomeningeal disease.
  • Participants with diffuse intrinsic pontine glioma (DIPG) are not eligible for this study.
  • Unresolved acute effects of any prior therapy of grade >= 2, except for adverse events (AEs) not constituting a safety risk by investigator judgement.
  • Use =< 10 days (or =< 5 half-lives, whichever is shorter) prior to day 1 or anticipated need for food or drugs known to be strong or moderate Cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or strong CYP3A inducers.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to TMZ or pamiparib (BGB-290).
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Female participants of childbearing potential must not be pregnant or breast-feeding. Female participants of childbearing potential must have a negative serum or urine pregnancy test within 7 days of first dose.
  • Human immunodeficiency virus (HIV)-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pamiparib (BGB-290) and TMZ. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy.
  • Participants with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Joseph M. Sanzari Children's Hospital at Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Yale University

    New Haven, Connecticut, 06520

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • University of California, San Francisco

    San Francisco, California, 94143

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Target Validation/Phase1 Study of BGB-290 in Combination With Temozolomide in Adolescent and Young Adult IDH1/2 Newly Diagnosed and Recurrent Mutant Gliomas

This phase I trial studies the side effects and best dose of BGB-290 and temozolomide in treating adolescents and young adults with IDH1/2-mutant grade I-IV glioma that is newly diagnosed or has come back. BGB-290 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving BGB-290 and temozolomide may work better in treating adolescents and young adults with IDH1/2-mutant grade I-IV glioma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the safety and tolerability of the combination of Poly (ADP-Ribose) polymerase (PARP) inhibitor BGB-290 (BGB-290) and temozolomide (TMZ) in adolescent and young adult (AYA) subjects with IDH1/2-mutant glioma, including the maximum tolerated dose (MTD) and characterization of dose-limiting toxicities (DLTs) in both, newly diagnosed and recurrent treatment arms.

With the completion of ABTC1801, a Phase I/II Study of BGB-290 with Temozolomide in Recurrent Gliomas with IDH1/2 Mutations, a maximum tolerated dose (MTD) for adults has been found. This study will advance to evaluate preliminary efficacy using this dose in patients 13-25 years of age.

EXPLORATORY OBJECTIVES:

  1. Evaluate the preliminary efficacy of BGB-290 and temozolomide in terms of progression free survival (PFS) and overall survival (OS) in Arm A and B stratified by tumor diagnosis, calculated using the Kaplan-Meier method with a goal of improving the historical high grade glioma progression free survival of 10% and overall survival of 20% at 2 years.

II. Assess the mutational landscape studies via whole-exome sequencing (WES).

III. Assessment of gene expression patterns using ribonucleic acid (RNA) sequencing (RNAseq).

IV. Assess the methylation profiling with Infinium methylation assays.

  1. Assess the oncometabolite profiling via liquid chromatography (LC)/mass spectrometry (MS)-MS.

VI. Assess the intratumoral drug level assessments via LC/MS-MS.

VII. To assess Quality of Life (QOL) and cognitive measures in adolescent and young adult patients with newly diagnosed and recurrent mutant gliomas.

VIII. To assess patient and/or proxy satisfaction with study participation via patient-reported outcome (PRO) measures in the context of race ethnicity and other health related social risks.

IX. To assess on therapy toxicity in the context of race, ethnicity and other health related social risks.

OUTLINE: Participants are assigned to 1 of 2 cohorts. The dose escalation component of the trial has been completed, which included patients ages 13-17 and the study will proceed with enrolling patients ages 13-25 years old onto the expansion cohort and target validation component at the ABTC pre-determined dose.

Arm A: Newly diagnosed IDH1/2-mutant high-grade glioma patients receive PARP inhibitor BGB-290 orally (PO) twice daily (BID) on days 1-28 and temozolomide PO daily on days 1-21. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

Arm B: Recurrent IDH1/2-mutant low-grade or high-grade glioma patients receive PARP inhibitor BGB-290 orally (PO) twice daily (BID) on days 1-28 and temozolomide PO daily on days 1-21. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

COHORT B0: Recurrent IDH1/2-mutant low-grade or high-grade glioma patients receive PARP inhibitor BGB-290 PO for 7 days pre-surgery at the ABTC-determined MTD. After recovery from surgery (14-28 days), the patient will proceed to the efficacy component of the trial.

After completion of study treatment, patients are followed up for 5 years. If participants are co-enrolled on the PNOC COMP protocol, participants will be followed under the PNOC COMP protocol until death or withdrawal from study.

Being tested
PARP Inhibitor BGB-290, Temozolomide (TMZ)
Medical subject headings
Glioblastoma, Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PARP Inhibitor BGB-290Drug

    Also called BGB-290, Pamiparib

    Given PO

  • Temozolomide (TMZ)Drug

    Also called CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831

    Given PO

Study groups in NCT03749187
Study groupRoleWhat they receive
Arm A (Pamiparib (BGB-290), Temozolomide (TMZ))ExperimentalParticipants with grades III-IV newly diagnosed IDH1/2 mutant glioma receive 60mg pamiparib (BGB-290) PO BID on days 1-28 and 20mg temozolomide (TMZ) PO daily on days 1-21. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
Receives: Drug: PARP Inhibitor BGB-290; Drug: Temozolomide (TMZ)
Arm B (BGB-290, Temozolomide)ExperimentalParticipants with grades I-IV recurrent IDH1/2 mutant glioma receive 60mg PARP inhibitor pamiparib (BGB-290) PO BID on days 1-28 and 20mg temozolomide PO daily on days 1-21. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Cohort B0: Participants who are surgical candidates with grades I-IV recurrent IDH1/2 mutant glioma receive 60mg PARP inhibitor BGB-290 PO BID for 7 days, pre-surgery. After recovery from surgery, participants receive PARP inhibitor BGB-290 PO BID on days 1-28 and 20mg temozolomide PO daily on days 1-21. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
Receives: Drug: PARP Inhibitor BGB-290; Drug: Temozolomide (TMZ)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of participants with Dose Limiting Toxicities (DLTs)

    Events occurring on or after treatment on Day 1 will be classified using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Adverse events leading to treatment discontinuation will be listed.

    Measured: Up to 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Nov 2018
  2. Study start3 Apr 2019
  3. Primary completion30 Jun 2026 (estimated)
  4. Study completion30 Jul 2029 (estimated)

Resources

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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
78 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03749187
Sponsor's protocol ID
18083
Other IDs
NCI-2018-02345, PNOC017
Acronym
PNOC017
Status last verified
Mar 2026
First submitted
19 Nov 2018
Last updated
13 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Individual participant data after de-identification.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PARP Inhibitor BGB-290 and Temozolomide (TMZ) in people with Glioblastoma and IDH1 Gene Mutation, run by University of California, San Francisco at 11 sites in United States.

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 32 inclusion and 19 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: under way, not looking for participants, as of the sponsor's last update on 13 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. 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 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.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Proportion of participants with Dose Limiting Toxicities (DLTs) (time frame: Up to 28 days). 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 NCT03749187.

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 13 Mar 2026.

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