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

Primary Purpose

Glioblastoma

Status
Completed
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Temozolomide+Metformin
Temozolomide+Placebo
Sponsored by
Yong-Kil Hong
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma focused on measuring Glioblastoma

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • National Cancer Center Korea
  • Seoul National University Bundang Hospital
  • Ajou University Hospital
  • Chonnam National University Hwasun Hospital
  • Incheon St. Mary's Hospital
  • Seoul National University Hospital
  • Severance Hospital
  • Konkuk University Hospital
  • Asan Medical Center
  • Samsung Medical Center
  • Seoul St Mary's Hospital
  • Saint Vincent's Hospital, Korea

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Temozolomide+metformin

Temozolomide+placebo

Arm Description

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/day 1 week(8th~14th day) = 1,500mg/day 2 weeks(15th ~28th day) = 2,000mg/day 2nd to 6th cycle (20 weeks) = 2,000mg/day

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/day 1 week(8th~14th day) = 1,500mg/day 2 weeks(15th~28th day) = 2,000mg/day 2nd to 6th cycle (20 weeks) = 2,000mg/day

Outcomes

Primary Outcome Measures

Comparison of progression-free survival obtained from progression-free survival curve
Comparison of progression-free survival obtained from progression-free survival curve

Secondary Outcome Measures

Response Rate
Tumor Response Rate
Tumor control probability
Tumor control probability
6 month progression free survival
6 month progression free survival
6 month overall survival
6 month overall survival
Assessment of the quality of life of cancer patients
EORTC QLQ-C30 and EORTC QLQ-BN20

Full Information

First Posted
July 29, 2017
Last Updated
September 8, 2021
Sponsor
Yong-Kil Hong
Collaborators
Saint Vincent's Hospital, Korea, Incheon St.Mary's Hospital, National Cancer Center, Korea, Konkuk University Hospital, Seoul National University Bundang Hospital, Samsung Medical Center, Seoul National University Hospital, Asan Medical Center, Ajou University School of Medicine, Severance Hospital, Chonnam National University Hospital, Seoul St. Mary's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03243851
Brief Title
Study on Low Dose Temozolomide Plus Metformin or Placebo in Patient With Recurrent or Refractory Glioblastoma
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
November 21, 2016 (Actual)
Primary Completion Date
December 31, 2020 (Actual)
Study Completion Date
December 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Yong-Kil Hong
Collaborators
Saint Vincent's Hospital, Korea, Incheon St.Mary's Hospital, National Cancer Center, Korea, Konkuk University Hospital, Seoul National University Bundang Hospital, Samsung Medical Center, Seoul National University Hospital, Asan Medical Center, Ajou University School of Medicine, Severance Hospital, Chonnam National University Hospital, Seoul St. Mary's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma
Keywords
Glioblastoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Arm 1 : Low dose temozolomide+metformin Arm 2 : Low dose temozolomide+placebo
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double blinded
Allocation
Randomized
Enrollment
81 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Temozolomide+metformin
Arm Type
Experimental
Arm Description
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/day 1 week(8th~14th day) = 1,500mg/day 2 weeks(15th ~28th day) = 2,000mg/day 2nd to 6th cycle (20 weeks) = 2,000mg/day
Arm Title
Temozolomide+placebo
Arm Type
Placebo Comparator
Arm Description
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/day 1 week(8th~14th day) = 1,500mg/day 2 weeks(15th~28th day) = 2,000mg/day 2nd to 6th cycle (20 weeks) = 2,000mg/day
Intervention Type
Drug
Intervention Name(s)
Temozolomide+Metformin
Intervention Description
Low dose temozolomide+metformin for 24 weeks
Intervention Type
Drug
Intervention Name(s)
Temozolomide+Placebo
Intervention Description
Low dose temozolomide+placebo for 24 weeks
Primary Outcome Measure Information:
Title
Comparison of progression-free survival obtained from progression-free survival curve
Description
Comparison of progression-free survival obtained from progression-free survival curve
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Response Rate
Description
Tumor Response Rate
Time Frame
4 weeks, 8 weeks, 16 weeks, 24 weeks thereafter every 24 weeks up to 96 weeks
Title
Tumor control probability
Description
Tumor control probability
Time Frame
4 weeks, 8 weeks, 16 weeks, 24 weeks thereafter every 24 weeks up to 96 weeks
Title
6 month progression free survival
Description
6 month progression free survival
Time Frame
24 weeks
Title
6 month overall survival
Description
6 month overall survival
Time Frame
24 weeks
Title
Assessment of the quality of life of cancer patients
Description
EORTC QLQ-C30 and EORTC QLQ-BN20
Time Frame
4 weeks, 8 weeks, 16 weeks, 24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Karnofsky performance status(KPS) ≥ 60% Age ≥ 19 years old At least 4 weeks after operation or chemotherapy 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 Be informed of the nature of the study and obtained a written informed consent A legal representative agrees to the trial when a subject is unable to communicate smoothly due to neurologic defect 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: Pregnant or breast feeding Cancer history within 5 years excluding cancer in the skin cells and cervix Active infections within two weeks Leptomeningeal metastasis Patients diagnosed with diabetes Hypersensitive or intolerance to Metformin Patients who are currently taking Metformin, sulfonylureas, thiazolidinediones, and insulin, regardless of reason 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 Those who have participated in other clinical trials may not recover from the toxicity of the treatment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yong-Kil Hong, MD.,PhD.
Organizational Affiliation
Seoul St. Mary's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Cancer Center Korea
City
Ilsan
State/Province
Gyeonggi-Do
ZIP/Postal Code
10408
Country
Korea, Republic of
Facility Name
Seoul National University Bundang Hospital
City
Seongnam-si
State/Province
Gyeonggi-Do
ZIP/Postal Code
13620
Country
Korea, Republic of
Facility Name
Ajou University Hospital
City
Suwon-si
State/Province
Gyeonggi-Do
ZIP/Postal Code
16499
Country
Korea, Republic of
Facility Name
Chonnam National University Hwasun Hospital
City
Hwasun
State/Province
Jeollanam-Do
ZIP/Postal Code
58128
Country
Korea, Republic of
Facility Name
Incheon St. Mary's Hospital
City
Incheon
ZIP/Postal Code
21431
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Severance Hospital
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Konkuk University Hospital
City
Seoul
ZIP/Postal Code
05030
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Seoul St Mary's Hospital
City
Seoul
ZIP/Postal Code
06591
Country
Korea, Republic of
Facility Name
Saint Vincent's Hospital, Korea
City
Suwon-si
ZIP/Postal Code
16247
Country
Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

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

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