NCT06095375

Regorafenib With Temozolomide With or Without RT in MGMT-Methylated, IDH Wild-type GBM Patients

Regorafenib in Combination With Temozolomide With or Without Radiotherapy in Patients With Newly Diagnosed MGMT-Methylated, IDH Wild-type Glioblastoma. A Phase I Dose-finding Study

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 21 (actual)
• Sponsor: Istituto Oncologico Veneto IRCCS · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study will evaluate the addition of regorafenib to standard of care treatment with TMZ as adjuvant therapy, and in combination with TMZ+RT as concomitant therapy. The standard of care for newly diagnosed GBM (ndGBM) includes surgical resection to the extent that is safely feasible, followed by RT plus concomitant TMZ chemotherapy, and up to 6 months of adjuvant TMZ. The dose escalation will be explored following a "3+3" design, escalating oral doses of regorafenib in combination with adjuvant (maintenance) TMZ (cohort A) to estimate the MTD of regorafenib as adjuvant (maintenance) therapy. After finding the MTD in the Adjuvant Therapy dose escalation, the Concomitant Therapy (cohort B) dose escalation will start, exploring escalating oral doses of regorafenib in combination with concomitant TMZ+RT, to estimate the MTD of regorafenib as concomitant therapy.

Conditions

• Glioblastoma, IDH-wildtype
• MGMT-Methylated Glioblastoma

Interventions

Type	Name	Description
DRUG	Regorafenib	Cohort A (Adjuvant/Maintenance Phase). The Adjuvant (Maintenance) Therapy dose escalation will explore three dose levels of regorafenib (e.g., 80 mg, 120 mg and 160 mg; level-1: regorafenib 40 mg will be evaluated in case of DLT during regorafenib 80 mg) administered in combination with adjuvant TMZ to evaluate the initial toxicity of regorafenib and TMZ Cohort B (Concomitant Phase) Therapy dose escalation will explore three dose levels of regorafenib (e.g., 80 mg, 120 mg and 160 mg; level -1: regorafenib 40 mg will be evaluated in case of DLT during regorafenib 80 mg) administered in combination with TMZ and RT.
DRUG	Temozolomide	Following a "3+3" design, in cohort A three patients will be administered temozolomide 150-200 mg/m2 for 5 consecutive days every 28 days until 6-12 cycles and regorafenib daily for 21 days, with a 1-week washout period at dose of 80 mg (level 1), 120 mg (level 2), or 160 mg (level 3) (regorafenib 40 mg- level -1). As a general rule, one cycle will last 28 days (day 1-28); however, in the event of treatment prolongation, the cycle period will be extended. In cohort B,During concomitant therapy phase: temozolomide 75 mg/m2/die for 42 (max 49 days) consecutive days (concomitant with radiation therapy).

Timeline

• Start date: 2022-07-04
• Primary completion: 2024-10-09
• Completion: 2025-12-22
• First posted: 2023-10-23
• Last updated: 2026-01-09

Locations

2 sites across 1 country: Italy