ACTIVE_NOT_RECRUITING

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

Conditions

Glioblastoma IDH1 Gene Mutation IDH2 Gene Mutation Low Grade Glioma Malignant Glioma Recurrent Glioblastoma Recurrent WHO Grade II Glioma Recurrent WHO Grade III Glioma WHO Grade II Glioma WHO Grade III Glioma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2019-04-03

Study Completion:2029-07-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT03749187

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:13 Years to 39 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
* 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. * 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.	* 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: * 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.

Inclusion Criteria

Exclusion Criteria

* 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.
* 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.

* 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:
* 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.

Contacts and Locations

Principal Investigator

Sabine Mueller, MD, PhD

PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Study Locations (Sites)

Children's Hospital Los Angeles

Los Angeles, California, 90027

United States

University of California, San Francisco

San Francisco, California, 94143

United States

Yale University

New Haven, Connecticut, 06520

United States

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287

United States

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

United States

Washington University School of Medicine

St Louis, Missouri, 63110

United States

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

Hackensack, New Jersey, 07601

United States

Duke University Medical Center

Durham, North Carolina, 27710

United States

Oregon Health and Science University

Portland, Oregon, 97239

United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104

United States

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105

United States

Collaborators and Investigators

Sponsor: University of California, San Francisco

Sabine Mueller, MD, PhD, PRINCIPAL_INVESTIGATOR, University of California, San Francisco

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2019-04-03

Study Completion Date2029-07-30

Study Record Updates

Study Start Date2019-04-03

Study Completion Date2029-07-30

Terms related to this study

Additional Relevant MeSH Terms

Glioblastoma
IDH1 Gene Mutation
IDH2 Gene Mutation
Low Grade Glioma
Malignant Glioma
Recurrent Glioblastoma
Recurrent WHO Grade II Glioma
Recurrent WHO Grade III Glioma
WHO Grade II Glioma
WHO Grade III Glioma