Clinical trial NCT06780930: Phase 3 Study of Vorasidenib (S095032/AG-881) in Asian Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 orIDH2 Mutation
Official title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo- Controlled Study of Vorasidenib (S095032/AG-881) in Asian Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Residual or Recurrent Grade 2 IDH Mutant Glioma
Lead sponsor: Servier
Sponsor class: INDUSTRY
First posted: 2025-01-17
Enrollment: 58
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to determine the efficacy, safety, and pharmacokinetics of vorasidenib in Asian participants with residual or recurrent Grade 2 glioma with an IDH1 or IDH2 mutation. The study will begin with a safety lead-in (SLI) phase and then will transition to a randomized double-blind placebo-controlled phase. During the study participants will have study visits on day 1 and 15 of the first two cycles, and then only on day 1 of treatment cycles in the frequency included in the study schedule of assessments. All participants will have an end of treatment visit within 7 days after their last dose of study treatment. Approximately 28 (+5) days after treatment has ended, a safety follow-up visit will occur. Study visits may include questionnaires, blood tests, ECG, vital signs, and a physical examination. Beginning at the end of treatment visit participants will be contacted by phone every 6 months for overall survival up to 5 years after the last participant is randomized or until death, withdrawal of consent from overall study participation, lost to follow-up, or sponsor ending the study, whichever occurs first.


Eligibility criteria: Inclusion Criteria:

* Be at least 12 years of age (for Randomized Double-Blind phase) and weigh at least 40 kg.
* Have a Karnofsky Performance Scale (KPS) score (for participants ≥16 years of age) or Lansky Play Performance Scale (LPPS) score (for participants \<16 years of age) of ≥80%.
* Have Grade 2 oligodendroglioma or astrocytoma per WHO 2016 criteria.
* Have had at least 1 prior surgery for glioma with the most recent one having occurred at least 1 year (-1 month) and not more than 5 years (+3 months) before randomization, and no other prior anticancer therapy, including radiotherapy and not be in need of immediate chemotherapy or radiotherapy.
* 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
* Have MRI-evaluable, measurable, non-enhancing disease, as confirmed by the BIRC for double blind part.

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.
* Concurrent active malignancy except for a) curatively resected nonmelanoma skin cancer or b) curatively treated carcinoma in situ. Participants with previously treated malignancies are eligible provided they have been disease-free for 3 years at Screening.
* Have any other acute or chronic medical or psychiatric condition that may increase the risk associated with the study participation or investigational product administration or may interfere with the interpretation of study results.
* Have 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.

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Approximately 1.5 years
Secondary outcomes:
measure: Dose limiting toxicities (DLTs) (for open-label Safety Lead In (SLI) phase)
timeFrame: Through Cycle 1 (28 days)
measure: Number of adverse events (AEs), serious adverse events (SAEs), and AEs leading to discontinuation or death
timeFrame: Through the safety follow up visit, 28 days after the last dose (approximately 6.5 years)
measure: Severity of AEs
timeFrame: Through the safety follow up visit, 28 days after the last dose (approximately 6.5 years)
measure: Time-To-Next-Intervention (TTNI)
timeFrame: Through the PFS Follow-up (approximately 6.5 years)
measure: Tumor Growth Rate (TGR) as assessed by volume
timeFrame: Through the PFS Follow-up (approximately 6.5 years)
measure: Objective response
timeFrame: Through the PFS Follow-up (approximately 6.5 years)
measure: Time to response
timeFrame: Through the PFS Follow-up (approximately 6.5 years)
measure: Duration of response
timeFrame: Through the PFS Follow-up (approximately 6.5 years)
measure: Overall survival
timeFrame: Through the Overall Survival Follow-up (approximately 6.5 years)
measure: Plasma concentrations of vorasidenib
timeFrame: Through the end of treatment visit, within 7 days after the last dose (approximately 6.5 years)
measure: Number of seizures by month
timeFrame: Through the end of treatment visit, within 7 days after the last dose (approximately 6.5 years)
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: The Second People's Hospital of Shenzhen
state: Guangdong
city: Chendu
country: China
facility: West China Hospital Sichuan University
state: Sichuan
city: Beijing
country: China
facility: Tiantan Hospital
city: Beijing
country: China
facility: Bejing Tsinghua Changgung Hospital
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Science
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Beijing
country: China
facility: Sanbo Brain Hospital, Capital Medical University
city: Beijing
country: China
facility: Xuanwu Hospital Capital Medial University
city: Fuzhou
country: China
facility: The First Affilated Hospital of Fujian Medical University
city: Guangzhou
country: China
facility: SUN Yat-Sen University Cancer Center
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
city: Shanghai
country: China
facility: Huashan Hospital Fudan University
city: Xi'an
country: China
facility: The Second Affiliated Hospital of Air Force Military Medical University
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital,
Study officials:
References: