Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation MedDRA version: 20.0 Level: PT Classification code 10018338 Term: Glioma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: vorasidenib
Product Code: AG-881 citrate
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: vorasidenib
CAS Number: 2316810-02-1
Current Sponsor code: AG-881
Other descriptive
Sponsors
Institut de Recherches Internationales Servier (I.R.I.S)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Be at least 12 years of age and weigh at least 40 kg. • Have Grade 2 oligodendroglioma or astrocytoma per WHO 2016 criteria. • Have had at least 1 prior surgery for glioma (biopsy, sub-total resection, gross-total resection), with the most recent surgery having occurred at least 1 year (-1 month) and not more than 5 years (+3 months) before the date of randomization, and no other prior anticancer therapy, including chemotherapy and radiotherapy, and not be in need of immediate chemotherapy or radiotherapy in the opinion of the Investigator. • Have confirmed IDH1 (IDH1 R132H/C/G/S/L mutation variants tested) or IDH2 (IDH2 R172K/M/W/S/G mutation variants tested) gene mutation status disease by central laboratory testing during the Prescreening period and available 1p19q status by local testing (eg, fluorescence in situ hybridization [FISH], comparative genomic hybridization [CGH] array, sequencing) using an accredited laboratory. • Have MRI-evaluable, measurable, non-enhancing disease, as confirmed by the blinded independent review committee (BIRC) • Have a Karnofsky Performance Scale (KPS) score (for subjects =16 years of age) or Lansky Play Performance Scale (LPPS) score (for subjects >16 years of age) of =80%. Are the trial subjects under 18? yes Number of subjects for this age range: 18 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 289 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 34
Exclusion criteria
Exclusion criteria: • Have had any prior anticancer therapy other than surgery (biopsy, sub-total resection, gross-total resection) for treatment of glioma including systemic chemotherapy, radiotherapy, vaccines, small-molecules, IDH inhibitors, investigational agents, laser ablation, etc. • Have features assessed as high-risk by the Investigator, including brainstem involvement either as primary location or by tumor extension, clinically relevant functional or neurocognitive deficits due to the tumor in the opinion of the Investigator (deficits resulting from surgery are allowed), or uncontrolled seizures (defined as persistent seizures interfering with activities of daily life AND failed 3 lines of antiepileptic drug regimens including at least 1 combination regimen).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the efficacy of vorasidenib based on radiographic progression-free survival (PFS) per blinded independent review committee (BIRC) compared with placebo in subjects with residual or recurrent Grade 2 glioma with an IDH1 or IDH2 mutation.;Secondary Objective: Key Secondary: • To demonstrate the efficacy of vorasidenib based on time to next intervention (TTNI) compared with placebo. Other Secondary. To evaluate: • The safety and tolerability of vorasidenib. • vorasidenib and placebo with respect to tumor growth rate (TGR) as assessed by volume per the BIRC. • the efficacy of vorasidenib and placebo based on objective response, complete response (CR) + partial response (PR), time to response, time to CR+PR, duration of response, and duration of CR+PR, with response assessed per the BIRC and the Investigator. • vorasidenib and placebo with respect to overall survival (OS). • vorasidenib and placebo with respect to health-related quality of life (HRQoL) as assessed by the Functional Assessment of Cancer Therapy – Brain (FACT-Br) questionnaire. • vorasidenib and placebo with respect to PFS per the Investigator assessment. • the pharmacokinetics (PK) of vorasidenib and its circulating metabolite AGI 69460 in plasma.;Primary end point(s): Radiographic PFS as assessed by the BIRC per modified Response Assessment for Neuro-oncology for Low-Grade Gliomas [RANO-LGG];Timepoint(s) of evaluation of this end point: The primary endpoint is PFS, defined as the time from randomization to the first occurrence of radiographic PD by modified RANO-LGG assessed by the BIRC or death from any cause, whichever occurs earlier. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary endpoint is TTNI. Other secondary efficacy endpoints are TGR, objective response, CR+PR, time to response, time to CR+PR, duration of response, duration of CR+PR, OS, FACT-Br scores and PFS by the Investigator. Safety/PK: • Adverse events, serious adverse events (SAEs), and AEs leading to discontinuation or death, and severity of AEs • Safety laboratory parameters, vital signs, 12-lead electrocardiograms (ECGs), evaluation of left ventricular ejection fraction (LVEF), Karnofsky Performance Scale (KPS)/Lansky Play-Performance Scale (LPPS), and concomitant medications. • Serial or sparse blood sampling at specified time points for determination of plasma concentration-time profiles and PK parameters of vorasidenib and its circulating metabolite AGI-69469.;Timepoint(s) of evaluation of this end point: TTNI: from randomization to initiation of first subsequent anticancer therapy or death due to any cause TGR as assessed by volume: % increase in tumor volume every 6 months OS: from date of randomization to date of death due to any cause OR: best overall response of CR,PR,MR CR+PR: best overall response of CR or PR Time to response: from date of randomization to first documented CR,PR or MR Time to CR+PR: from date of randomization to first documented CR or PR for subjects with CR or PR Duration of response: from date of first documented CR,PR or MR to the earlier of the date of death due to any cause or first documented radiographic PD Duration of CR+PR: from date of first documented CR or PR to the earlier of the date of death due to any cause or first documented radiographic PD | — |
Countries
Canada, France, Germany, Israel, Italy, Netherlands, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactClinical Studies Department
Institut de Recherches Internationales Servier
Outcome results
None listed