Vorasidenib Guided by AGX PET in Recurrent/Low-grade Glioma

NCT07469735 | Not Yet Recruiting

• 1 other identifier: HIM-2025-0674
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this prospective, single-arm, open-label clinical trial is to evaluate whether 18F-AGX PET imaging can be used to assess early treatment response and metabolic changes in adult patients with recurrent or residual WHO 2021 grade 2-3 IDH-mutant diffuse glioma receiving Vorasidenib therapy. IDH-mutant diffuse gliomas often show slow tumor growth, making early treatment response difficult to evaluate using conventional structural imaging such as magnetic resonance imaging (MRI). Clinical endpoints such as progression-free survival (PFS) and overall survival (OS) typically require long follow-up periods to detect treatment effects. Therefore, the development of sensitive and noninvasive imaging methods for early evaluation of therapeutic response is needed. This study aims to determine whether metabolic changes detected by 18F-AGX PET during Vorasidenib treatment are associated with tumor structural changes and clinical outcomes. The main questions it aims to answer are:

• Whether early changes in tumor metabolic activity measured by 18F-AGX PET, including percentage change in maximum tumor-to-background ratio (TBRmax), are associated with changes in tumor growth rate (TGR) measured by MRI during treatment.
• Whether early metabolic response detected by 18F-AGX PET imaging after initiation of Vorasidenib treatment can predict subsequent disease progression or tumor growth dynamics. Participants enrolled in this study will receive oral Vorasidenib once daily for 12 treatment cycles (28 days per cycle), with dosing based on body weight. Participants will:
• Undergo baseline MRI and 18F-AGX PET imaging following surgery for recurrent or residual disease.
• Receive oral Vorasidenib continuously for 12 cycles.
• Undergo MRI scans at baseline and during treatment cycles 1, 2, 3, 6, 9, and 12 to assess structural tumor changes.
• Undergo 18F-AGX PET/CT scans at baseline and during treatment cycles 1, 2, 3, 6, and 12 to assess metabolic tumor activity.
• Provide serial blood samples for laboratory safety monitoring, including hematologic and biochemical testing.
• Undergo magnetic resonance spectroscopy (MRS) to quantify intratumoral 2-hydroxyglutarate (2-HG) levels as an indicator of IDH mutation-associated metabolic activity. Participants will be followed for imaging-based disease progression using RANO criteria and for treatment-related adverse events during the study period. This study will evaluate the feasibility of using 18F-AGX PET imaging as a noninvasive imaging biomarker for early response assessment in IDH-mutant diffuse glioma patients receiving targeted IDH inhibition therapy with Vorasidenib.

Conditions

Glioma; Diffuse Glioma; Recurrent Gliomas

Keywords

IDH Mutation; Vorasidenib; Positron Emission Tomography; Treatment Response

Outcome Measures

Primary Outcomes (1)

• Change in Tumor Metabolic Activity Assessed by 18F-AGX PET

  Percentage change from baseline in maximum tumor-to-background ratio (TBRmax) measured by 18F-AGX PET imaging during Vorasidenib treatment.

  Up to 12 treatment cycles (approximately 12 months)

Secondary Outcomes (3)

• Tumor Growth Rate Assessed by MRI

  From baseline to the end of Cycle 12 (each cycle is 28 days; approximately 12 months)

• Diagnostic Accuracy of 18F-AGX PET for IDH Mutation Detection

  At baseline imaging assessment

• Incidence of Treatment-Related Adverse Events

  From the first dose of Vorasidenib to the end of Cycle 12 (each cycle is 28 days; approximately 12 months)

Study Arms (1)

Vorasidenib Treatment with 18F-AGX PET Assessment

EXPERIMENTAL

Participants receive oral Vorasidenib once daily for up to 12 treatment cycles (28 days per cycle). Serial 18F-AGX PET imaging and MRI assessments are performed during treatment to evaluate metabolic and structural tumor changes associated with IDH-targeted therapy.

Drug: Oral Vorasidenib administered once daily for up to 12 treatment cycles (28 days per cycle) as IDH-targeted therapy in participants with recurrent or residual IDH-mutant diffuse glioma.

Interventions

Oral Vorasidenib administered once daily for up to 12 treatment cycles (28 days per cycle) as IDH-targeted therapy in participants with recurrent or residual IDH-mutant diffuse glioma. DRUG

Positron emission tomography (PET) imaging performed using the investigational IDH-targeted radiotracer 18F-AGX to assess metabolic tumor activity during Vorasidenib treatment.

Vorasidenib Treatment with 18F-AGX PET Assessment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or molecularly confirmed WHO 2021 grade 2 or 3 IDH1/2-mutant diffuse glioma with recurrent or residual disease
• At least one measurable non-enhancing lesion (≥1 cm × ≥1 cm) on postoperative T2/FLAIR MRI
• Eligible for Vorasidenib treatment
• Age ≥18 years
• Karnofsky Performance Status (KPS) score ≥80
• Adequate hematologic function
• Adequate renal function
• Adequate hepatic function
• Ability to provide written informed consent

You may not qualify if:

• Prior treatment with radiotherapy, chemotherapy, or IDH inhibitors
• Known contraindications to Vorasidenib
• Contraindications to PET/CT imaging
• Uncontrolled hyperglycemia
• Pregnancy or breastfeeding
• Inability to undergo repeated intravenous injections
• Known hypersensitivity to imaging agents or study-related medications
• Use of strong CYP1A2 inhibitors or CYP2C19 or CYP3A substrates with narrow therapeutic index
• Any serious comorbid condition that may interfere with study participation or safety

Sponsors & Collaborators

• Huashan Hospital: lead
• SCU West China Lecheng Hospital: collaborator

Study Sites (1)

Huashan Hospital

Shanghai, Shanghai Municipality, 201100, China

Location

Related Publications (2)

• Galldiks N, Werner JM, Stetter I, Puhr HC, Nakuz TS, Stoffels G, Albert NL, Langen KJ, Lohmann P, Preusser M. Evaluation of early metabolic changes following vorasidenib using FET PET in patients with IDH-mutant gliomas. Neurooncol Adv. 2024 Nov 29;6(1):vdae210. doi: 10.1093/noajnl/vdae210. eCollection 2024 Jan-Dec.

  PMID: 39737092 BACKGROUND

• Cloughesy TF, van den Bent MJ, Touat M, Blumenthal DT, Peters KB, Ellingson BM, Clarke JL, Mendez J, Yust-Katz S, Welsh L, Mason WP, Ducray F, Umemura Y, Nabors B, Holdhoff M, Hottinger AF, Arakawa Y, Sepulveda JM, Wick W, Soffietti R, Perry J, Giglio P, de la Fuente M, Maher E, Bottomley A, Tron AE, Yi D, Zhao D, Pandya SS, Steelman L, Hassan I, Wen PY, Mellinghoff IK; INDIGO trial investigators. Vorasidenib in IDH1-mutant or IDH2-mutant low-grade glioma (INDIGO): secondary and exploratory endpoints from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2025 Dec;26(12):1665-1675. doi: 10.1016/S1470-2045(25)00472-3. Epub 2025 Oct 29.

  PMID: 41175888 BACKGROUND

MeSH Terms

Conditions

Glioma

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Zhifeng Shi, MD

  Huashan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhifeng Shi, MD

CONTACT

+86 21 64280718; shizhifeng@fudan.edu.cn

Shan Jiang, MD

CONTACT

+86 21 64280718; jsscosmos@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: This is an open-label study. Participants, care providers, and investigators are aware of treatment assignment. Imaging-based outcome assessments are performed by an independent central review committee blinded to clinical information and treatment response.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor, Associate Chief Physician, Deputy Director of Huashan Clinical Research Institute, Huashan Hospital, Fudan University

Model Details: This is a prospective, single-arm interventional study in which all enrolled participants receive oral Vorasidenib treatment for up to 12 treatment cycles. Serial 18F-AGX PET imaging and MRI assessments are performed during treatment to evaluate metabolic and structural tumor changes associated with IDH-targeted therapy. No comparator or control group is included.

Study Record Dates

• First Submitted: March 5, 2026
• First Posted: March 13, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 13, 2026

Record last verified: 2026-03

Locations

CN (1)