Study on Low Dose Temozolomide Plus Metformin or Placebo in Patient With Recurrent or Refractory Glioblastoma

Glioblastoma Clinical Trial

— METT  

Official title:

Efficacy and Safety of Low Dose Temozolomide Plus Metformin as Combination Chemotherapy Compared With Low Dose Temozolomide Plus Placebo in Patient With Recurrent or Refractory Glioblastoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03243851
• Other study ID #: KNOG-1501
• Status: Completed
• Phase: Phase 2
• Start date: November 21, 2016
• Est. completion date: December 31, 2020

Study information

• Verified date: September 2021
• Source: Seoul St. Mary's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A phase 2 clinical trial for the efficacy and safety of low dose Temozolomide plus metformin as combination chemotherapy compared with low dose Temozolomide plus placebo in patient with recurrent or refractory Glioblastoma

Description:

Studies will investigate the efficacy and safety of low dose Temozolomide with Metformin or placebo for the patients with recurrent or refractory Glioblastoma.

The dosage of the Metformin will follow the domestically permitted dose to minimize side effects.

The patients will be allocated randomly to arm 1(experimental) and arm 2(placebo controlled) and administered the investigational products for up to 6 cycle. Each cycle consists of 4 weeks.

After 6 cycle(24 weeks), the patients will be checked progression and survival every 24 weeks up to 96 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

1. Progressive or recurrent Glioblastoma conformed by histopathological or radiological diagnosis. Progressive or recurrent Glioblastoma during or after standard therapy (Temozolomide after Temozolomide and radiation therapy; Stupp regimen) after histopathological diagnosis of Glioblastoma Recurrence or progression is diagnosed according to histopathological diagnosis or revised RANO(Response Assessment in Neuro-Oncology) criteria c

2. Karnofsky performance status(KPS) = 60%

3. Age = 19 years old

4. At least 4 weeks after operation or chemotherapy

5. Normal in hematological finding, liver and kidney function

• Hematology ANC > 1.500/mm³, Platelet > 100,000/mm³, WBC > 3×10^9/L, Hemoglobin > 9g/dL

• Liver function Total Bilirubin level = 1.5×ULN(in case of isolated hyperbilirubinemia =2.5 x ULN) AST / ALT < 2.5×ULN

• Renal function Serum creatinine = 1.5mg/dL

6. Be informed of the nature of the study and obtained a written informed consent

7. A legal representative agrees to the trial when a subject is unable to communicate smoothly due to neurologic defect

8. If a fertile woman who has been confirmed negative to a urine or blood pregnancy test within 28 days prior to the trial

Exclusion Criteria:

1. Pregnant or breast feeding

2. Cancer history within 5 years excluding cancer in the skin cells and cervix

3. Active infections within two weeks

4. Leptomeningeal metastasis

5. Patients diagnosed with diabetes

6. Hypersensitive or intolerance to Metformin

7. Patients who are currently taking Metformin, sulfonylureas, thiazolidinediones, and insulin, regardless of reason

8. Other serious diseases or medical conditions that include :

• Patients who suffer from unstable heart disease despite treatment.

• Patients having a heart attack within 6 months prior to the start of trial

• Patients who suffer from severe nerve or psychosis that includes dementia or strokes.

• Patients with an uncontrolled infection

• Patient with uncontrolled hypertension, congestive heart failure, unstable angina, or incomplete arrhythmia

9. Those who have participated in other clinical trials may not recover from the toxicity of the treatment.

Related Conditions & MeSH terms

• Glioblastoma

Intervention

Drug:
• Temozolomide+Metformin
Low dose temozolomide+metformin for 24 weeks
• Temozolomide+Placebo
Low dose temozolomide+placebo for 24 weeks

Locations

Country	Name	City	State
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun	Jeollanam-Do
Korea, Republic of	National Cancer Center Korea	Ilsan	Gyeonggi-Do
Korea, Republic of	Incheon St. Mary's Hospital	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-Do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Konkuk University Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul St Mary's Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	Ajou University Hospital	Suwon-si	Gyeonggi-Do
Korea, Republic of	Saint Vincent's Hospital, Korea	Suwon-si

Sponsors (13)

Lead Sponsor	Collaborator
Yong-Kil Hong	Ajou University School of Medicine, Asan Medical Center, Chonnam National University Hospital, Incheon St.Mary's Hospital, Konkuk University Hospital, National Cancer Center, Korea, Saint Vincent's Hospital, Korea, Samsung Medical Center, Seoul National University Bundang Hospital, Seoul National University Hospital, Seoul St. Mary's Hospital, Severance Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of progression-free survival obtained from progression-free survival curve	Comparison of progression-free survival obtained from progression-free survival curve	24 weeks
Secondary	Response Rate	Tumor Response Rate	4 weeks, 8 weeks, 16 weeks, 24 weeks thereafter every 24 weeks up to 96 weeks
Secondary	Tumor control probability	Tumor control probability	4 weeks, 8 weeks, 16 weeks, 24 weeks thereafter every 24 weeks up to 96 weeks
Secondary	6 month progression free survival	6 month progression free survival	24 weeks
Secondary	6 month overall survival	6 month overall survival	24 weeks
Secondary	Assessment of the quality of life of cancer patients	EORTC QLQ-C30 and EORTC QLQ-BN20	4 weeks, 8 weeks, 16 weeks, 24 weeks