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
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
Parallel
Vorasidenib
DrugVorasidinib will be administered orally once daily at a dose of 40 mg in continuous 28-day cycles
Vorasidenib Placebo
DrugMatched oral vorasidenib placebo will be administered once daily in continuous 28-day cycles
Progression-free survival (PFS) by local assessment
Progression-free survival (PFS) will be defined as the number of days from date of enrolment to the date of earliest disease progression based on Response Assessment (RANO 2.0) or to the date of death due to any cause, if disease progression did not occur (the date of progression or death or censoring - date of enrolment + 1). Patients who received new anti-cancer therapy or cancer-related surgery or radiotherapy prior to progression or death will not be censored at the last assessment where the patient was documented as progression free prior to the new anti-cancer therapy or cancer-related surgery or radiotherapy, instead progression after start of new therapy or surgery will be considered a valid event for PFS.
PFS by local assessment
Progression-free survival (PFS) will be defined as the number of days from date of enrolment to the date of earliest disease progression based on Response Assessment (RANO 2.0) or to the date of death due to any cause, if disease progression did not occur (the date of progression or death or censoring - date of enrolment + 1). Patients who received new anti-cancer therapy or cancer-related surgery or radiotherapy prior to progression or death will not be censored at the last assessment where the patient was documented as progression free prior to the new anti-cancer therapy or cancer-related surgery or radiotherapy, instead progression after start of new therapy or surgery will be considered a valid event for PFS.
Progression-free survival (PFS) from the start of radiotherapy
Progression-free survival from the start of radiotherapy will be defined as the number of days from date of start of radiotherapy till progression or censoring with the same rules as for PFS.
Overall Survival
Overall survival (OS) will be defined as the number of days from date of enrolment to the date of death due to any cause (the date of death or censoring - date of enrolment +1). If a subject has not died, the data will be censored at the last date documented to be alive. Patients still alive (or not known to have died before the cutoff date) or lost to follow-up are censored at the last date known to be alive.
Overall Response
All patients included in the study must be assessed for their overall response treatment based on RANO 2.0 criteria at each assessment of the disease, from the start of study treatment until disease progression , even if there is a major protocol treatment deviation, if they are ineligible, or not followed/ /re-evaluated. Each patient will be assigned one of the following categories: complete response (CR), partial response (PR), minor response (MR, applicable only to non-enhancing disease), stable disease (SD), Equivocal progressive disease (EqPD), progressive disease (PD), early death (ED) or not evaluable (NE). Early death is defined as any death occurring before the first per protocol time point of tumour re-evaluation.
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European Organisation for Research and Treatment of Cancer - EORTC
Lead sponsor
Canadian Cancer Trials Group
Collaborator
Olivia Newton-John Cancer Research Institute
Collaborator