VALIENT: Phase 1 Clinical Trial of VorAsidenib in Combination With Lomustine In Patients With rEcurrent IDH-mutaNT Glioma Harboring IDH1 and/or IDH2 Mutations
Megan Mantica
Summary
This study will test the hypothesis that vorasidenib in combination with lomustine will be safe and tolerable. The overall goal of this study is to identify the optimal vorasidenib dose that can be tested in a subsequent phase 2 study to determine the efficacy of vorasidenib in combination with lomustine in patients with recurrent IDH mutant gliomas.
Description
IDH-mutant gliomas are the most common primary malignant brain tumors in adults under the age of 50 and accounts for approximately 10-15% of all glioma diagnoses each year (Van den Bent et al 2023). While lower grade gliomas (LGG) encompassing World Health Organization (WHO) grades 2 and 3 are less aggressive than their higher-grade counterparts, treatment is not curative, and most patients develop tumor recurrence in which there are a paucity of effective treatment options. Mutations in IDH1 and 2 occur in upwards of 80% of patients with LGG (Yan et al 2009) and drive specific epigenetic prog…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: Subjects must meet all of the following inclusion criteria to be eligible for enrollment: 1. Age ≥18 years. 2. Karnofsky performance status score of ≥ 60%. 3. Be able to understand and willing to sign informed consent or assent as determined by local requirements. 4. Be willing to comply with scheduled visits, treatment plans, and laboratory tests, including serial peripheral blood sampling and during the study. 5. Must have recurrent IDH-mutant oligodendroglioma or astrocytoma grade 2-4 harboring IDH1 and/or IDH2 mutation per WHO 2021 criteria (Louis et al, 2021). 6. Mus…
Interventions
- DrugVorasidenib
Oral targeted therapy for IDH1- or IDH2-mutant grade 2 astrocytoma or oligodendroglioma, approved for use after surgery.
- DrugLomustine
An alkylating nitrosourea compound used in chemotherapy. It is highly lipid-soluble thus it crosses the blood-brain barrier. Primarily used in treating brain tumors.
Location
- UMPC Hillman Cancer CenterPittsburgh, Pennsylvania