Vorasidenib as Maintenance Treatment After First-line Chemoradiotherapy in IDH-mutant Grade 2 or 3 Astrocytoma: a Placebo-controlled, Triple-blind, Randomized Phase III Study (VIGOR)
The main goal of VIGOR is to demonstrate that vorasidenib maintenance therapy improves locally assessed progression-free survival (PFS) from enrolment compared to placebo in patients with IDH-mutant, CNS5 WHO Grade 2 or 3 astrocytoma following the completion of first-line chemoradiotherapy. The primary endpoint is Progression-free survival (PFS), as assessed locally from the date of enrolment using the RANO 2.0 criteria. In this a comparative, randomized (1:1), triple blinded, multicentre phase III superiority trial with one stopping rule for efficacy and futility after end of enrolment, participants in the experimental arm will receive vorasidenib orally once daily at a dose of 40 mg in continuous 28-day cycles while participants in the control arm will receive a matched oral placebo once daily in continuous 28-day cycles
• 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.