Evaluate the Efficacy and Safety of Atorvastatin Combined With Temozolomide in the Treatment of Glioblastoma

Glioblastoma (GBM) is the primary intracranial malignant tumor with the highest morbidity and mortality, and the 5-year survival rate is less than 10%. The number of primary diagnostic patients and deaths of GBM in China ranks first in the world every year, which seriously threatens people's life and health. At present, the clinical treatment strategy of maximum surgical resection combined with concurrent chemo- and radio-therapy and TTF treatment is still not satisfactory, and the median survival time of GBM patients is only 14.4 months. Statins inhibit cholesterol production with few side effects and are widely used for cholesterol control in patients with hyperlipidemia. In recent years, statins have shown good anti-tumor effect. Our previous study found that statins can block the malignant progression of glioma mediated by EGFR pathway. Therefore, the investigators report a clinical study protocol designed to evaluate the clinical efficacy of a comprehensive treatment strategy of atorvastatin (ATO) combined with temozolomide (TMZ) in primary and recurrent glioblastomas with high EGFR expression.

The investigators designed a multicenter, single-arm, double-blind, phase II clinical trial to evaluate the efficacy and safety of oral ATO combined with TMZ in EGFR-high expressing GBM. After informed consent was signed by the patient or authorized family members, the patients were treated with the current STUPP regimen and ATO (20mg, qn) orally. The patients were regularly followed up for 52 weeks after treatment. The primary endpoint was progression-free survival (PFS), which was defined as the time from the start of GBM surgery to tumor progression (recurrence) or death. The secondary end point was the rate of tumor control, which was defined as the proportion of patients with a complete response, a partial response, or a stable disease that had shrunk or remained stable for a given period of time. Safety will be assessed during the study by monitoring of regular MRI scans, laboratory tests (liver function, lipid profile, blood routine), electrocardiography, vital signs (blood pressure, pulse, temperature), and weight.

The results of this clinical trial will provide key information on whether the oral combination of atorvastatin and temozolomide prolongs PFS in EGFR-high GBM patients with efficacy and safety.

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma, IDH-wildtype
• Intervention / Treatment: Drug: Atorvastatin 20mg

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chunsheng Kang; Phone Number: +8618622998838; Email: kang97061@tmu.edu.cn
• Study Contact Backup: Name: Xiaoteng Cui; Phone Number: +8613516251495; Email: xiaotengcui@tmu.edu.cn

Study Locations

• China
  • Tianjin, China, 300052
    • Recruiting
    • Tianjin Medical University General Hospital
    • Contact: Chunsheng Kang; Phone Number: +8602260817499; Email: kang97061@tmu.edu.cn
    • Contact: Xiaoteng Cui; Phone Number: +8602260817481; Email: xiaotengcui@tmu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. age ≥18 years old and < 60 years old, both sexes;
2. sufficient evidence of glioma by MRI scan;
3. According to the 2021 WHO latest classification, the molecular pathology of postoperative glioma samples was diagnosed as WHO 4 glioblastoma;
4. The immunohistochemical results of postoperative glioma samples showed that EGFR score was 3 (standard: 0 was negative, 1-3 was positive);
5. normal blood routine and liver function;
6. fully understand the nature of the trial and sign the informed consent;
7. be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures;
8. no serious diseases or accidents requiring surgery;
9. normal immune function.

Exclusion Criteria:

1. allergy to atorvastatin or its components;
2. concomitant use of clarithromycin, itraconazole, ritonavir, saquinavir, lopinavir, cyclosporine, rifampicin, efavirenz, digoxin, warfarin, oral contraceptives;
3. other tumors (except glioma), hematological diseases or other known multiple organ failure, history of myasthenia gravis, heart failure, cerebral hernia and other serious complications;
4. History of cardiac insufficiency, arrhythmia, retinopathy, acute hepatic porphyrin, hepatic and renal insufficiency, obesity, uncontrolled diabetes and other metabolic diseases;
5. abnormal liver function or liver disease, including uncontrolled hepatitis;
6. other diseases that might interfere with the study, as determined by 2 attending neurosurgeons;
7. patients enrolled in a clinical trial within the past 4 weeks;
8. pregnant or lactating patients;
9. patients with poor compliance who could not complete the treatment;
10. other conditions that made the patient ineligible for enrollment as determined by the study investigator;
11. patients with a history of HIV and/or HBV/HCV or presence of HIV/HCV;
12. patients with a history of tuberculosis or known existence of tuberculosis;
13. patients with severe infection or signs/symptoms of infection within 2 weeks before the first dose of study drug;
14. patients who received live attenuated vaccine within 4 weeks before the first dose of study drug;
15. patients with previous solid organ transplantation or hematopoietic stem cell transplantation.

Those who meet any of the above criteria will not be selected.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atorvastatin administrating group; According to the clinical standard dose of lipid-lowering drugs, the subjects were enrolled in this study. After 2 weeks of glioma surgery, one tablet of liptor was taken orally every night on the basis of STUPP protocol.	Drug: Atorvastatin 20mg; Liptor is a capsule in the form of 20 mg, once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression-free survival	progression-free survival	the time from the start of GBM surgery to tumor progression (recurrence) or death, whichever came first, assessed up to 52 weeks
Overall survival	Overall survival	the time from the start of GBM surgery to the day of death from any cause, whichever came first, assessed up to 52 weeks
Tumor control rate	Tumor control rate	Changes in tumor size before and after treatment, assessed up to 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hepatic burden of GBM patients after receiving atorvastatin administration	This outcome is evaluation of hepatic burden of GBM patients after receiving atorvastatin administration. Since participant is enrolled in this research, peripheral blood will be collected for testing ALT, AST, GGT, ALP, TP, ALB, GLB, A/G, TBIL, DBIL, and IBIL. The physiological parameters of these index are as follows: ALT: 0~40 U/L; AST: 0~40 U/L; GGT: 0~40 U/L; ALP: 40~110 U/L; TP: 65~85 g/L; ALB: 40~55 g/L; GLB: 20~40 g/L; A/G: 1.5~2.5: 1; TBIL: 0~23 μmol/L; DBIL: 0~8 μmol/L; IBIL: 1~14 μmol/L.	1, 3, and 6 months after enrollment
Percentage of participants with treatment-related adverse events	This outcome is evaluation of safety and tolerability during combination therapy of atorvastatin and STUPP protocol. Percentage of participants with treatment-related adverse events as assessed by CTCAE v5.0.	1, 3, and 6 months after enrollment

Collaborators and Investigators

• Sponsor: Tianjin Medical University General Hospital
• Investigators: Principal Investigator: Chunsheng Kang, Tianjin Medical University General Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): February 28, 2026
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: February 20, 2024
• First Submitted That Met QC Criteria: March 21, 2024
• First Posted (Actual): March 25, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: IRB2024-YX-037-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: According to the clinical standard dose of lipid-lowering drugs, the subjects were enrolled in this study. After 2 weeks of glioma surgery, one tablet of liptor was taken orally every night on the basis of other treatments.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes