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

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

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

Study Overview

• Status: Completed
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: Temozolomide+Metformin; Drug: Temozolomide+Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Incheon, Korea, Republic of, 21431
    • Incheon St. Mary's Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 06591
    • Seoul St Mary's Hospital
  • Seoul, Korea, Republic of, 05030
    • Konkuk University Hospital
  • Suwon-si, Korea, Republic of, 16247
    • Saint Vincent's Hospital, Korea
  • Gyeonggi-Do
    • Ilsan, Gyeonggi-Do, Korea, Republic of, 10408
      • National Cancer Center Korea
    • Seongnam-si, Gyeonggi-Do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital
    • Suwon-si, Gyeonggi-Do, Korea, Republic of, 16499
      • Ajou University Hospital
  • Jeollanam-Do
    • Hwasun, Jeollanam-Do, Korea, Republic of, 58128
      • Chonnam National University Hwasun Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Temozolomide+metformin; Temozolomide : 1 cycle of 4 weeks with daily dose 50mg/m2(BSA: Body Surface Area) up to 6 cycles for 24 weeks Metformin : 1st cycle (4 weeks)1 week(1st~7th day) = 1,000mg/day1 week(8th~14th day) = 1,500mg/day2 weeks(15th ~28th day) = 2,000mg/day; 2nd to 6th cycle (20 weeks) = 2,000mg/day	Drug: Temozolomide+Metformin; Low dose temozolomide+metformin for 24 weeks
Placebo Comparator: Temozolomide+placebo; Temozolomide : 1 cycle of 4 weeks with daily dose 50mg/m2(BSA: Body Surface Area) up to 6 cycles for 24 weeks Placebo: 1st cycle (4 weeks)1 week(1st~7th day) = 1,000mg/day1 week(8th~14th day) = 1,500mg/day2 weeks(15th~28th day) = 2,000mg/day; 2nd to 6th cycle (20 weeks) = 2,000mg/day	Drug: Temozolomide+Placebo; Low dose temozolomide+placebo for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate	Tumor Response Rate	4 weeks, 8 weeks, 16 weeks, 24 weeks thereafter every 24 weeks up to 96 weeks
Tumor control probability	Tumor control probability	4 weeks, 8 weeks, 16 weeks, 24 weeks thereafter every 24 weeks up to 96 weeks
6 month progression free survival	6 month progression free survival	24 weeks
6 month overall survival	6 month overall survival	24 weeks
Assessment of the quality of life of cancer patients	EORTC QLQ-C30 and EORTC QLQ-BN20	4 weeks, 8 weeks, 16 weeks, 24 weeks

Collaborators and Investigators

• Sponsor: Yong-Kil Hong
• Collaborators: National Cancer Center, Korea; Samsung Medical Center; Seoul St. Mary's Hospital; Asan Medical Center; Chonnam National University Hospital; Seoul National University Hospital; Seoul National University Bundang Hospital; Ajou University School of Medicine; Severance Hospital; Saint Vincent's Hospital, Korea; Incheon St.Mary's Hospital; Konkuk University Hospital
• Investigators: Principal Investigator: Yong-Kil Hong, MD.,PhD., Seoul St. Mary's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2016
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: July 29, 2017
• First Submitted That Met QC Criteria: August 4, 2017
• First Posted (Actual): August 9, 2017

Study Record Updates

• Last Update Posted (Actual): September 9, 2021
• Last Update Submitted That Met QC Criteria: September 8, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Glioblastoma
• 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; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide; Metformin
• Other Study ID Numbers: KNOG-1501

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No