Vorasidenib in CNS WHO Grade 2 IDH-mutant Diffuse Glioma (VIOLETA)

Vorasidenib in CNS WHO Grade 2 IDH-mutant Diffuse Glioma: A Multicenter, Prospective, Non-interventional Study in Germany

The goal of this prospective, observational study VIOLETA is to collect real-world data on vorasidenib treatment in a broad patient population. Though vorasidenib can be administered from 12 years old, VIOLETA focuses on adult patients with IDH1- or IDH2-mutant WHO grade 2 glioma who receive vorasidenib following surgery according to the current SmPC. Thus, VIOLETA will evaluate for the first-time treatment with vorasidenib in German clinical routine. To gain knowledge about how vorasidenib treatment affects patients' well-being, the primary objective of the study is to assess patients' quality of life. Further patient-relevant endpoints addressed by this study will include seizure burden, PFS, Objective Response Rate (ORR), TTNI, safety as well as factors affecting treatment decision making.

Study Overview

• Status: Recruiting
• Conditions: Glioma
• Intervention / Treatment: Drug: Vorasidenib

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: iOMEDICO; Phone Number: +49761152420; Email: information@iomedico.com

Study Locations

• Germany
  • Heidelberg, Germany
    • Recruiting
    • Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg
    • Contact: Wolfgang Wick, Prof. Dr.; Phone Number: +496221567075; Email: nct.neuroonko@med.uni-heidelberg.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients (at least 40 kg) with predominantly non-enhancing grade 2 astrocytoma or oligodendroglioma with an IDH1 or IDH2 mutation who only had surgical intervention and are not in immediate need of radiotherapy or chemotherapy.

Description

Inclusion Criteria:

• Age ≥18 years
• WHO grade 2 astrocytoma or oligodendroglioma
• Presence of IDH1- or IDH2-mutation
• Surgical intervention
• No immediate need of radiotherapy or chemotherapy according to the treating physician
• Decision for treatment with vorasidenib as per current SmPC
• Signed written informed consent*
• Willingness to participate in Patient-Reported Outcome (PRO) assessment in German language
• Other criteria according to current SmPC * Patients are allowed to be enrolled up to 6 weeks after their first intake of vorasidenib but must still be on treatment at the time of enrollment

Exclusion Criteria:

• Participation in an interventional clinical trial
• Patient unable to consent
• Other contraindications according to current SmPC.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate Quality of Life (QoL) by the Functional Assessment of Cancer Therapy - Brain (FACT-Br) questionnaire over the course of treatment	Evaluate QoL by the FACT-Br questionnaire over the course of treatment. Change from baseline in the FACT-Br total score over time. The FACT-Br total score ranges from 0 to 200, with higher scores indicating better quality of life.	baseline, up to 72 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess parameters of physicians' treatment decision making using a questionnaire	Frequency of distinct parameters affecting therapy choice; questionnaire completed by treating physician.	Baseline
Evaluate Quality of Life (QoL) by using the Functional Assessment of Cancer Therapy - Brain (FACT-Br) questionnaire at start and during course of vorasidenib treatment	Evaluate QoL by using the FACT-Br questionnaire at start and during course of vorasidenib treatment. Change from baseline over time for all other scales of the FACT-Br. For all scales, the higher the score the better quality of life.	baseline, up to 72 months
Assess seizure activity and severity at baseline and during treatment: Proportion of patients with baseline seizure activity	Proportion of patients with baseline seizure activity is defined as at least 1 seizure in the previous 30 days prior to vorasidenib treatment start	baseline, up to 72 months
Assess seizure activity and severity at baseline and during treatment: event rate of seizures	Exposure adjusted event rate of seizures according to patient-reported outcome (patient diary)	baseline, up to 72 months
Assess seizure activity and severity at baseline and during treatment: event rate of seizures with loss of consciousness	Exposure adjusted event rate of seizures with loss of consciousness according to PRO (patient diary)	baseline, up to 72 months
Assess seizure activity and severity at baseline and during treatment: incidence rate of seizures	Exposure adjusted incidence rate of seizures according to patient-recorded outcome	baseline, up to 72 months
Assess seizure activity and severity at baseline and during treatment: incidence rate of seizures with loss of consciousness	Exposure adjusted incidence rate of seizures according to patient-reported outcome	baseline, up to 72 months
Assess seizure activity and severity at baseline and during treatment: Change from baseline of seizures	Change from baseline of seizures reported by the patients during course of treatment	max. 72 months; from patient-specific study start to end of study (during vorasidenib treatment and follow-up)
Assess seizure activity and severity at baseline and during treatment: Change from baseline of seizures with loss of consciousness	Change from baseline of seizures with loss of consciousness reported by the patients during course of treatment	baseline, up to 72 months
Assess effectiveness in routine treatment: Progression-free survival	PFS ist defined as time interval measured from the day of first vorasidenib administration to first progression or death, whichever comes first. Patients without tumor progression or death at the time of analysis will be censored at their date of last contact.	baseline, up to 72 months
Assess effectiveness in routine treatment: Overall Survival (OS)	OS is defined as the time interval measured form the day of first vorasidenib administration to time of death from any cause. Time to last contact will be used if a patient has no documented date of death and OS for the patient will be considered censored.	baseline, up to 72 months
Assess effectiveness in routine treatment: Objective response rate (ORR)	ORR is defined as the proportion of patients achieving Complete Response (CR), Partial Response (PR), or Minor Response (MR) as best response.	max. 72 months; from patient-specific study start to end of study (during vorasidenib treatment and follow-up)
Assess effectiveness in routine treatment: Disease Control Rate (DCR)	DCR is defined as proportion of patients with Complete Response, Partial Response, Minor Response or Stable Disease as best response.	baseline, up to 72 months
Assess effectiveness in routine treatment: Best response	Best response is defined as Complete Response (CR), Partial Response (PR), Minor Response (MR), Stable Disease (SD), or Progressive Disease (PD))	baseline, up to 72 months
Assess effectiveness in routine treatment: Time to next intervention (TTNI)	Time to next intervention is defined as time from first administration of vorasidenib until initiation of next intervention (i.e., subsequent antineoplastic treatment, surgery, chemotherapy or radiotherapy) or death, whichever comes first.	baseline, up to 72 months
Assess drug safety: Incidence of (serious) adverse events ((S)AEs)	Incidence of (serious) AEs ((S)AEs) as characterized by type, frequency, severity and seriousness.	Baseline up to 30 days after vorasidenib treatment
Assess drug safety: Incidence of (serious) adverse drug reactions ((S)ADRs)	Incidence of (serious) adverse drug reactions ((S)ADRs) as characterized by type, frequency, severity and seriousness.	Baseline up to 30 days after vorasidenib treatment
Assess drug safety: Incidence of seizures reported as treatment-emergent adverse events (TEAEs)	Treatment-emergent adverse events (TEAE) are adverse events that were not present before medical treatment, or a pre-existing event that worsens in intensity or frequency during vorasidenib treatment and the following 30 days.	Baseline up to 30 days after vorasidenib treatment
Duration of treatment with vorasidenib	Describe treatment reality in detail: Duration of treatment with vorasidenib	baseline, up to 72 months
Frequency of treatment modifications with reasons	Describe treatment reality in detail: Frequency of treatment modifications with reasons	baseline, up to 72 months
Time to start of vorasidenib treatment after initial diagnosis	Describe treatment reality in detail: Time to start of vorasidenib treatment after initial diagnosis	Baseline
Time to start of vorasidenib treatment after surgery	Describe treatment reality in detail: Time to start of vorasidenib treatment after surgery	Baseline
Frequency of distinct subsequent antineoplastic therapies (systemic therapies including substances, surgeries, radiotherapies)	Describe treatment reality in detail: Frequency of distinct subsequent antineoplastic therapies (systemic therapies including substances, surgeries, radiotherapies)	baseline, up to 72 months
Anti-epileptic medication: Proportion of patients with anti-epileptic drug (AED) treatment at baseline	Proportion of patients with anti-epileptic drug treatment at baseline (i.e. 30 days prior treatment)	baseline, up to 72 months
Anti-epileptic medication: Proportion of patients with AED treatment during treatment	Proportion of patients with anti-epileptic drug treatment during treatment	baseline, up to 72 months
Anti-epileptic medication: Type of AED	Anti-epileptic medication during course of treatment	baseline, up to 72 months
Anti-epileptic medication: Doses of AED	Doses of anti-epileptic medication over the course of time	baseline, up to 72 months
Anti-epileptic medication: AED modifications	Type of anti-epileptic medication modifications	baseline, up to 72 months
Anti-epileptic medication: Reasons for AED modifications	Anti-epileptic medication modifications with reasons thereof	baseline, up to 72 months
Anti-epileptic medication: Frequency of patients under AED treatment after End of Treatment (EOT) of vorasidenib	Frequency of patients under AED treatment after EOT of vorasidenib (incl. dose)	from end of treatment to end of study, up to 72 months

Collaborators and Investigators

• Sponsor: iOMEDICO AG

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2025
• Primary Completion (Estimated): November 1, 2031
• Study Completion (Estimated): January 1, 2032

Study Registration Dates

• First Submitted: September 29, 2025
• First Submitted That Met QC Criteria: November 18, 2025
• First Posted (Estimated): November 21, 2025

Study Record Updates

• Last Update Posted (Actual): January 9, 2026
• Last Update Submitted That Met QC Criteria: January 7, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: diffuse; IDH-mutant; WHO Grade 2
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; vorasidenib
• Other Study ID Numbers: IOM-120529

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No