Vebreltinib Combined With Temozolomide for Glioblastoma (GBM) After Surgery

The Efficacy of Vebreltinib Combined With Temozolomide for Glioblastoma (GBM) After Surgery: a Study Protocol for a Prospective, Open-label ,Multi-center, Randomized, Controlled Trial in China

The purpose of this study is to explore the effects of Vebreltinib in primary glioblastoma patients receiving a combination therapy of chemotherapy (temozolomidel) and MET-TKI.

Study Overview

• Status: Not yet recruiting
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: Vebreltinib + Temozolomide; Drug: Temozolomide

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jinsong Wu, Professor; Phone Number: +86-13701707118; Email: wjsongc@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Aged 18-65 years, female or male
2. Newly diagnosed GBM (WHO grade 4) patients with maximal surgical resection
3. c-MET overexpression diagnosed by IHC
4. KPS ≥60

5. Adequate hematological, renal, and hepatic function.

   All patients should meet the following criteria:

   1. absolute neutrophil count (ANC) ≥1.5 × 109/L and platelet count≥100 × 109/L
   2. serum creatinine clearance ≥80 mL/min
   3. total bilirubin level ≤ 1.5 × ULN (except patients with Gilbert syndrome)
   4. aspartate aminotransferase (AST) ≤ 3.0 × ULN, alanine aminotransferase (ALT) ≤ 3.0 × ULN, and AST/ALT < 2.5 × ULN
6. The patient and his/her family members were informed and provided signed and informed consent

Exclusion Criteria:

1. Any previous postoperative treatment except for concurrent chemoradiotherapy;
2. Individuals unable to undergo cranial MRI examination;
3. Active hemorrhage detected by cranial CT or MRI scan before enrollment;
4. Uncontrolled hypertension;
5. Decompensated heart failure, unstable angina pectoris, acute myocardial infarction, or persistent and clinically significant arrhythmias within 3 months before enrollment;
6. Anti-HIV (+), or both anti-HCV and HCV-RNA (+), or HBsAg positive with HBV-DNA >1000IU/ml;
7. Individuals requiring long-term continuous use of hematopoietic growth factors or platelet transfusions;
8. Pregnant or lactating women;
9. Individuals who have received other clinical trial drugs within 30 days before the first dose of the study drug;
10. Individuals deemed unsuitable for participation in this clinical trial by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vebreltinib + Temozolomide; Participants received Vebreltinib (300 mg Bid) in combination with Temozolomide (150 mg/m2) treatment, every 4 weeks for up to 6 cycles (Induction).	Drug: Vebreltinib + Temozolomide; Vebreltinib is a capsule in the form of 25 mg and 100mg, twice daily. Participants received Vebreltinib (300 mg Bid) in combination with Temozolomide (150 mg/ m2) treatment, every 4 weeks for up to 6 cycles (Induction).
Active Comparator: Temozolomide; Participants received Temozolomide (150 mg/m2) treatment, every 4 weeks for up to 6 cycles (Induction).	Drug: Temozolomide; Participants received Temozolomide (150 mg/ m2) treatment, every 4 weeks for up to 6 cycles (Induction).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	The primary outcome is the PFS of patients, the time from randomization and group allocation to any recorded disease progression, and even death.	Every 4 weeks (±14 days) from enrollment until the last enrolled participant completes a 12-month follow-up or is lost to follow-up.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	The time from randomization and allocation to death for any reason	Every 4 weeks (±14 days) from enrollment until the last enrolled participant completes a 12-month follow-up or is lost to follow-up.
The Karnof sky Performance status scale (KPS)	The scale measures the levels of patient activity and medical needs. The score ranges from 100 (no signs of disease) to 0 (dead).	Every 4 weeks (±14 days) from enrollment until the last enrolled participant completes a 12-month follow-up or is lost to follow-up.
Objective response rate (ORR)	Objective response rate (ORR) = (CR + PR)/total number of cases × 100%. A complete response (CR) is defined as the disappearance of all target lesions. A partial response (PR) is defined as a reduction of at least 30% in the sum of diameters of the target lesions, considering the baseline sum diameters as a reference. The ORR will be determined by MRI according to the Response Evaluation Citeria in Solid Tumors (RECIST)	Every 4 weeks (±14 days) from enrollment until the last enrolled participant completes a 12-month follow-up or is lost to follow-up.
Incidence of adverse events (AEs)	Adverse events (CTC-Toxicity ≥ grade III) will be recorded and analyzed based on the Common Terminology Criteria for Adverse Events (CTC-AE)	Every 4 weeks (±14 days) from enrollment until the last enrolled participant completes a 12-month follow-up or is lost to follow-up.

Collaborators and Investigators

• Sponsor: Huashan Hospital
• Collaborators: Beijing Tiantan Hospital; Beijing Sanbo Brain Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 13, 2025
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: January 13, 2025
• First Submitted That Met QC Criteria: January 13, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 20, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Temozolomide; Vebreltinib
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: KY2024-754

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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