STUPP Regimen With or Without Lenvatinib for Newly Diagnosed Glioblastoma With MGMT Promoter Methylation

NCT07754734 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: IIT-2026-006
• Study Type: interventional
• Target: 138
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Glioma; Glioblastoma (GBM); MGMT-Methylated Glioblastoma

Keywords

Stupp regimen; Lenvatinib; phase II clinical trial; glioblastoma and MGMT promoter methylation

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival（PFS）

  defined as the time from enrollment to the first documented local-regional recurrence, distant metastasis, or death from any cause

  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

Secondary Outcomes (5)

• 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

• Best Overall Response (BOR)

  36 months

• 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.

• 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.

• 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.

Other Outcomes (1)

• Exploratory Endpoints (optional)

  Before the first dose, after the completion of radiotherapy, and at the time of disease progression, whichever came first, assessed up to 36 months.

Study Arms (2)

experimental group：Lenvatinib + TMZ + radiotherapy

EXPERIMENTAL

Lenvatinib + TMZ + radiotherapy：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.

Drug: Lenvatinib; Drug: TMZ (Temozolomide); Radiation: radiotherapy

control group：TMZ + radiotherapy

ACTIVE COMPARATOR

TMZ + radiotherapy：During RT, TMZ 75 mg/m² po QD; 4 weeks after RT, 6 cycles of TMZ (150-200 mg/m² po D1-D5, Q4W) maintenance.

Drug: TMZ (Temozolomide); Radiation: radiotherapy

Interventions

Lenvatinib DRUG

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.

experimental group：Lenvatinib + TMZ + radiotherapy

TMZ (Temozolomide) DRUG

Chemotherapy: TMZ Group: During RT, TMZ 75 mg/m² po QD; 4 weeks after RT, 6 cycles

control group：TMZ + radiotherapy; experimental group：Lenvatinib + TMZ + radiotherapy

radiotherapy RADIATION

Starts 2-6 weeks post-op; total dose 60 Gy (2.0 Gy/fraction, 30 fractions) over 6-7 weeks.

control group：TMZ + radiotherapy; experimental group：Lenvatinib + TMZ + radiotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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):
• ANC ≥ 1.5 × 10⁹/L; PLT ≥ 100 × 10⁹/L; Hb ≥ 90 g/L.
• Total bilirubin ≤ 1.5 × ULN.
• ALT, AST ≤ 3 × ULN.
• 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.

You may not qualify if:

• 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:
• Grade 4 non-hematological toxicity (except hair loss, nausea, vomiting).
• 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).

Sponsors & Collaborators

• Dongguan People's Hospital: lead

MeSH Terms

Conditions

Glioma; Glioblastoma

Interventions

lenvatinib; Temozolomide; Radiotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Central Study Contacts

Zhigang Liu, PostDoc Fellow

CONTACT

0769-28637916; zhigangliu1983@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: (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.

Study Record Dates

• First Submitted: June 23, 2026
• First Posted: August 10, 2026
• Study Start: August 10, 2026
• Primary Completion (Estimated): July 31, 2029
• Study Completion (Estimated): July 31, 2029
• Last Updated: August 10, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share