Vorasidenib Maintenance for IDH Mutant Astrocytoma

Launched by EUROPEAN ORGANISATION FOR RESEARCH AND TREATMENT OF CANCER - EORTC · Jan 30, 2025

Keywords

ClinConnect Summary

The clinical trial titled "Vorasidenib Maintenance for IDH Mutant Astrocytoma" is studying whether a medication called vorasidenib can help patients with a specific type of brain tumor known as IDH-mutant astrocytoma. This trial is for adults aged 18 and older who have completed their initial treatment, which includes radiation and chemotherapy. The aim is to see if taking vorasidenib daily for several weeks can keep the tumor from growing or worsening compared to a placebo (a fake pill with no medication) over time.

To participate in this trial, individuals must have been diagnosed with IDH-mutant astrocytoma and must have already undergone surgery and completed their first-line treatment. Those interested should be in generally good health, with stable blood counts and organ function. Participants can expect to take either vorasidenib or a placebo daily for 28-day cycles and to have regular check-ups, including MRI scans, to monitor their health. It's also important to note that the trial is not yet recruiting participants, so interested individuals will need to wait until it begins.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Before participant's enrolment, written informed consent must be given according to ICH/GCP, and national/local regulations.
• • Age ≥ 18 years
• • Integrated diagnosis of astrocytoma, IDH-mutant, WHO CNS5 grade 2 or 3, per local assessment
• • Documented IDH1 or IDH2 mutation based on local testing of tumour tissue
• • At least 1 prior surgery for glioma (biopsy, partial resection, gross-total resection)
• • Completed first-line standard of care radiotherapy (minimum 50.4 Gy, photons or protons allowed) followed by SoC adjuvant chemotherapy (i.e., either 4-12 cycles of temozolomide or 2-6 cycles of PCV).
• • Adequate bone marrow function: absolute neutrophil counts ≥ 1.5 x 109/L, haemoglobin ≥ 9 g/dL, platelets 100 x 109/ L.
• • Adequate renal function: serum creatinine ≤ 2.0 x ULN, or creatine clearance \> 40 mL/min, as calculated based on CKD-EPI 2021 formula.
• * Adequate hepatic function:
• • Total bilirubin ≤ 1.5 × ULN (except for patients with Gilbert's syndrome who are excluded if total bilirubin \> 3.0 × ULN or direct bilirubin ≥1.5 × ULN)
• • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 x ULN.
• • Alkaline phosphatase (ALP) ≤ 2.5 x ULN.
• • Recovered from any clinically relevant toxicity of the previous chemoradiotherapy cycle unless stable and manageable per investigator´s judgement
• • WHO performance status 0-2
• • Stable or decreasing corticosteroid dose, or no use of corticoids, for at least 7 days prior to enrollment.
• • Baseline brain MRI available, as defined in the schedule of assessments
• • Available FFPE tumour tissue from prior neurosurgery for central biobanking and translational research
• • Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within two weeks prior to enrolment.
• • Participants of childbearing / reproductive potential should use two adequate methods of birth control, including a highly effective method and a barrier method during the study treatment period and for at least 90 days after the last dose of treatment.
• Exclusion Criteria:
• • Presence of 1p19q co-deletion, per local assessment.
• • Tumour recurrence or progression per RANO 2.0 criteria between first day of radiotherapy and enrolment, per local assessment
• • Last chemotherapy dose of first line chemoradiotherapy less than 6 weeks or more than 12 weeks before enrolment
• • Prior therapy with an IDH inhibitor or IDH vaccine
• • Any prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
• • Integrated diagnosis of astrocytoma, IDH-mutated, CNS5 WHO grade 4
• • Pregnancy or breastfeeding
• • Significant known active cardiac disease within 6 months before enrollment, including New York Heart Association Class III or IV congestive heart failure, myocardial infarction, unstable angina, and/or stroke.
• • Known hypersensitivity to any of the components of vorasidenib.
• • Ongoing use of medications that are CYP2C8, CYP2C9, CYP2C19, or CYP3A substrates with a narrow therapeutic index. Participants must be transferred to other medications before receiving the first dose of study drug.
• • Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, known positive human immunodeficiency virus antibody results, or AIDS-related illness.
• • Participants with a sustained viral response to HCV treatment or immunity to prior HBV infection will be permitted. Participants with chronic HBV that is adequately suppressed by institutional practice will be permitted.
• • • Known active inflammatory gastrointestinal disease, chronic diarrhea, previous gastric resection or lap band dysphagia, short-gut syndrome, gastroparesis, or other condition that limits the gastrointestinal absorption of drugs administered orally.
• • Gastroesophageal reflux disease under medical treatment is allowed (assuming no drug interaction potential).
• • Inability or known contraindication to undergo contrast media MRI.
• • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed and discussed with the patient before the enrolment in the trial.