Clinical Trial
PNOC017: 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
Patients will receive BGB-290 twice daily, once in the morning and once in the evening. Temozolomide will be administered once daily. Dosing should occur in the morning together with the BGB-290 dose. Patients will be instructed to swallow the capsules whole, in rapid succession, with water. Patients receiving trial medications (BGB-290 and TMZ) may continue on study therapy for up to 24 months from the time of study entry.
In the target validation component, patients will receive BGB-290 monotherapy at the Phase I determined maximum tolerated dose for 7 days prior to the additional resection. Tissue will be acquired to measure tumor drug levels and drug will be restarted 14-28 days after recovery from surgery.
The estimated incidence of primary CNS tumors in children and adolescents ≤ 19 years of age is 5.6 cases per 100,000 person years. As the most common CNS tumors in children and adolescents, gliomas possess a diverse range of clinical behavior. Pediatric malignant gliomas share molecular similarities with adult secondary GBM, and investigators have questioned whether IDH mutations can be found in AYA HGG. In patients 14 years of age or older, IDH1 mutation were found in 7 out of 20 (35%) pediatric gliomas treated on Children’s Oncology Group ACNS0423. A precision medicine analysis of pediatric brain tumors also showed IDH1 mutations to be particularly concentrated in the adolescent age group. In contrast to adult low-grade gliomas (LGG), pediatric LGGs classically do not exhibit IDH1/2 mutations and malignant progression is uncommon. Among recurrent pediatric LGG, however, there is a rare subset of adult-type IDH-mutant glioma. Our trial would enroll patients with recurrent LGG and newly diagnosed or recurrent HGG.
Determine the safety and tolerability of the combination of BGB-290 and temozolomide (TMZ) in 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.
The study is closed to accrual.
Funding is provided by BeiGene, CureSearch for Children’s Cancer and The Gateway Foundation
Patients will receive BGB-290 twice daily, once in the morning and once in the evening. Temozolomide will be administered once daily. Dosing should occur in the morning together with the BGB-290 dose. Patients will be instructed to swallow the capsules whole, in rapid succession, with water. Patients receiving trial medications (BGB-290 and TMZ) may continue on study therapy for up to 24 months from the time of study entry.
In the target validation component, patients will receive BGB-290 monotherapy at the Phase I determined maximum tolerated dose for 7 days prior to the additional resection. Tissue will be acquired to measure tumor drug levels and drug will be restarted 14-28 days after recovery from surgery.
The estimated incidence of primary CNS tumors in children and adolescents ≤ 19 years of age is 5.6 cases per 100,000 person years. As the most common CNS tumors in children and adolescents, gliomas possess a diverse range of clinical behavior. Pediatric malignant gliomas share molecular similarities with adult secondary GBM, and investigators have questioned whether IDH mutations can be found in AYA HGG. In patients 14 years of age or older, IDH1 mutation were found in 7 out of 20 (35%) pediatric gliomas treated on Children’s Oncology Group ACNS0423. A precision medicine analysis of pediatric brain tumors also showed IDH1 mutations to be particularly concentrated in the adolescent age group. In contrast to adult low-grade gliomas (LGG), pediatric LGGs classically do not exhibit IDH1/2 mutations and malignant progression is uncommon. Among recurrent pediatric LGG, however, there is a rare subset of adult-type IDH-mutant glioma. Our trial would enroll patients with recurrent LGG and newly diagnosed or recurrent HGG.
Determine the safety and tolerability of the combination of BGB-290 and temozolomide (TMZ) in 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.
The study is closed to accrual.
Funding is provided by BeiGene, CureSearch for Children’s Cancer and The Gateway Foundation
Sites Offering This Trial
- LOS ANGELES, CA Children’s Hospital Los Angeles
- BOSTON, MA Dana-Farber/Boston Children’s Cancer and Blood Disorders Center
- PORTLAND, OR Private: Doernbecher Children’s Hospital Oregon Health & Science University (OHSU)
- DURHAM, NC Duke University Medical Center
- BALTIMORE, MD Johns Hopkins Hospital
- HACKENSACK, NJ Joseph M. Sanzari Children’s Hospital at Hackensack University Medical Center
- MEMPHIS, TN St. Jude Children’s Research Hospital
- ST. LOUIS, MO St. Louis Children’s Hospital
- PHILADELPHIA, PA The Children’s Hospital of Philadelphia
- San Francisco, CA UCSF Benioff Children’s Hospitals
- NEW HAVEN, CT Yale University, Yale Cancer Center*
How to Enroll
If you believe your child or patient is eligible for this trial, contact the closest participating site or email us for more information.