Glioblastoma (GBM), Glioma, MGMT-Methylated Glioblastoma
Conditions
Keywords
Stupp regimen, Lenvatinib, phase II clinical trial, glioblastoma and MGMT promoter methylation
Brief summary
To compare the efficacy and safety of Lenvatinib combined with the standard Stupp regimen versus the standard Stupp regimen alone in the treatment of newly diagnosed glioblastoma with MGMT promoter methylation positive.
Interventions
DRUGLenvatinib
Chemotherapy:Lenvatinib-TMZ Group: During RT, TMZ 75 mg/m² po QD and Lenvatinib 20 mg po QD; 4 weeks after RT, 6 cycles of TMZ maintenance; Lenvatinib continues at 20 mg QD post-RT until progression or intolerable toxicity.
Chemotherapy: TMZ Group: During RT, TMZ 75 mg/m² po QD; 4 weeks after RT, 6 cycles
RADIATIONradiotherapy
Starts 2-6 weeks post-op; total dose 60 Gy (2.0 Gy/fraction, 30 fractions) over 6-7 weeks.
Sponsors
Dongguan People's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
(1) RT: 60 Gy/30 fractions over 6-7 weeks. (2) Chemo: TMZ group gets 75 mg/m² QD during RT, then 6 cycles of maintenance (150-200 mg/m² D1-D5, Q4W). Lenvatinib-TMZ group adds Lenvatinib (20 mg po QD) from Day 1 of RT through maintenance until progression or intolerable toxicity.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Newly diagnosed GBM confirmed by post-op pathology/biopsy, MGMT promoter methylation positive, no prior RT or chemo. * Surgery/biopsy ≤ 21 days before enrollment. * Age 18-75 years any gender. * KPS ≥ 70. * Organ function (no blood components or growth factors within 14 days): 1. ANC ≥ 1.5 × 10⁹/L; PLT ≥ 100 × 10⁹/L; Hb ≥ 90 g/L. 2. Total bilirubin ≤ 1.5 × ULN. 3. ALT, AST ≤ 3 × ULN. 4. Serum creatinine ≤ 1.5 × ULN or CrCl ≥ 50 mL/min. * Life expectancy ≥ 12 weeks. * Stable or tapering corticosteroid dose for 14 days. * Voluntary participation, signed informed consent, and good compliance.
Exclusion criteria
* Allergy to Lenvatinib, TMZ, or components. * Other malignancies within 5 years or concurrent, or prior anti-tumor therapy. * Concurrent participation in another clinical trial (except observational). * Comorbidities interfering with treatment: 1. Grade 4 non-hematological toxicity (except hair loss, nausea, vomiting). 2. Conditions interfering with oral drugs (dysphagia, chronic diarrhea, bowel obstruction). * Evidence of increased intracranial pressure (midline shift \> 5 mm, papilledema, vomiting, decreased consciousness). * History of drug/alcohol abuse. * Pregnancy or lactation. * Other conditions judged by the investigator (e.g., unstable heart/kidney disease, uncontrolled diabetes, mood disorders).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival（PFS） | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months | defined as the time from enrollment to the first documented local-regional recurrence, distant metastasis, or death from any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | From date of randomization until the date of first documented date of death from any cause, whichever came first, assessed up to 36 months | defined as the time from enrollment to death from any cause. |
| Best Overall Response (BOR) | 36 months | determined by modified RANO criteria for patients with incomplete tumor resection and documented postoperative residual tumor. |
| Safety evaluation | During the concurrent chemoradiotherapy phase; Weekly during maintenance chemotherapy cycles 1-6 (the worst result within each cycle will be recorded); At the end of treatment or disease progression. whichever came first, assessed up to 36 months. | Adverse events (AE) and serious adverse events (SAE) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE V5.0). |
| Function quality of Life | Before the concurrent chemoradiotherapy phase; Weekly before maintenance chemotherapy cycles 1-6 (the worst result within each cycle will be recorded); At the end of treatment or disease progression. whichever came first, assessed up to 36 months. | Aassessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 ( (EORTC QLQ-C30) : Scores are converted to 0-100 scale. Higher scores indicate better functioning and quality of life for functional and global health/QoL domains, while higher symptom scores indicate greater symptom burden. |
| Brain tumor symptom burden | Before the concurrent chemoradiotherapy phase; Weekly before maintenance chemotherapy cycles 1-6 (the worst result within each cycle will be recorded); At the end of treatment or disease progression. whichever came first, assessed up to 36 months. | Assessed using the EORTC QLQ-BN20: Scores are converted to 0-100 scale. Higher symptom domain scores indicate more severe disease-related symptoms. |
Contacts
CONTACTZhigang Liu, PostDoc Fellow
Outcome results
None listed