GlioblastomaPhase 2METTNCT03243851
Study on Low Dose Temozolomide Plus Metformin or Placebo in Patient With Recurrent or Refractory Glioblastoma
A Phase 2 study testing Temozolomide+Metformin in people with Glioblastoma, run by Yong-Kil Hong at 12 sites in South Korea.
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 Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Temozolomide+Metformin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 81 participants
- Where
- 12 sitesSouth Korea
- Study dates
- 21 Nov 2016to 31 Dec 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
South Korea12 sites
Chonnam National University Hwasun Hospital
Hwasun, Jeollanam-do, 58128
National Cancer Center Korea
Ilsan, Gyeonggi-do, 10408
Incheon St. Mary's Hospital
Incheon, 21431
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 13620
Seoul National University Hospital
Seoul, 03080
Severance Hospital
Seoul, 03722
Konkuk University Hospital
Seoul, 05030
Asan Medical Center
Seoul, 05505
Samsung Medical Center
Seoul, 06351
Seoul St Mary's Hospital
Seoul, 06591
Ajou University Hospital
Suwon, Gyeonggi-do, 16499
Saint Vincent's Hospital, Korea
Suwon, 16247
About this study
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
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
Read the 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.
- Conditions
- Glioblastoma
- Being tested
- Temozolomide+Metformin, Temozolomide+Placebo
- Keywords
- Glioblastoma
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Temozolomide+MetforminDrug
Low dose temozolomide+metformin for 24 weeks
Temozolomide+PlaceboDrug
Low dose temozolomide+placebo for 24 weeks
| Study group | Role | What they receive |
|---|---|---|
| Temozolomide+metformin | Experimental | Temozolomide :
1 cycle of 4 weeks with daily dose 50mg/m2(BSA: Body Surface Area) up to 6 cycles for 24 weeks
Metformin :
1. 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
2. 2nd to 6th cycle (20 weeks) = 2,000mg/day Receives: Drug: Temozolomide+Metformin |
| Temozolomide+placebo | Placebo comparator | Temozolomide :
1 cycle of 4 weeks with daily dose 50mg/m2(BSA: Body Surface Area) up to 6 cycles for 24 weeks
Placebo:
1. 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
2. 2nd to 6th cycle (20 weeks) = 2,000mg/day Receives: Drug: Temozolomide+Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of progression-free survival obtained from progression-free survival curve
Comparison of progression-free survival obtained from progression-free survival curve
Measured: 24 weeks
Secondary outcomes (5)
Response Rate
Tumor Response Rate
Measured: 4 weeks, 8 weeks, 16 weeks, 24 weeks thereafter every 24 weeks up to 96 weeks
Tumor control probability
Tumor control probability
Measured: 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
Measured: 24 weeks
6 month overall survival
6 month overall survival
Measured: 24 weeks
Assessment of the quality of life of cancer patients
EORTC QLQ-C30 and EORTC QLQ-BN20
Measured: 4 weeks, 8 weeks, 16 weeks, 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2017
- Study start21 Nov 2016
- Primary completion31 Dec 2020
- Study completion31 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Arm 1 : Low dose temozolomide+metformin Arm 2 : Low dose temozolomide+placebo
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yong-Kil Hong
- Sponsor type
- University, hospital or other
- 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
- Responsible party
- Sponsor-investigator, Yong-Kil Hong, Seoul St. Mary's Hospital
- Investigators
- Yong-Kil Hong, MD.,PhD., Principal investigator, Seoul St. Mary's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03243851
- Sponsor's protocol ID
- KNOG-1501
- Acronym
- METT
- Status last verified
- Sep 2021
- First submitted
- 29 Jul 2017
- Last updated
- 9 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Yoon WS, Chang JH, Kim JH, Kim YJ, Jung TY, Yoo H, Kim SH, Ko YC, Nam DH, Kim TM, Kim SH, Park SH, Lee YS, Yim HW, Hong YK, Yang SH. Efficacy and safety of metformin plus low-dose temozolomide in patients with recurrent or refractory glioblastoma: a randomized, prospective, multicenter, double-blind, controlled, phase 2 trial (KNOG-1501 study). Discov Oncol. 2023 Jun 6;14(1):90. doi: 10.1007/s12672-023-00678-3.
PubMed 37278858
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03243851
- Acronym / sponsor ID
- METT / KNOG-1501
- Conditions
- Glioblastoma
- Keywords
- Glioblastoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Yong-Kil HongUniversity, hospital or other
- 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
- Study start
- 21 Nov 2016 (actual)
- Primary completion
- 31 Dec 2020 (actual)
- Study completion
- 31 Dec 2020 (actual)
- First posted
- 9 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Arm 1 : Low dose temozolomide+metformin Arm 2 : Low dose temozolomide+placebo
| Arm | Type | Receives |
|---|---|---|
| Temozolomide+metformin | Experimental | Drug: Temozolomide+MetforminTemozolomide : 1 cycle of 4 weeks with daily dose 50mg/m2(BSA: Body Surface Area) up to 6 cycles for 24 weeks Metformin : 1. 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 2. 2nd to 6th cycle (20 weeks) = 2,000mg/day |
| Temozolomide+placebo | Placebo comparator | Drug: Temozolomide+PlaceboTemozolomide : 1 cycle of 4 weeks with daily dose 50mg/m2(BSA: Body Surface Area) up to 6 cycles for 24 weeks Placebo: 1. 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 2. 2nd to 6th cycle (20 weeks) = 2,000mg/day |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Temozolomide+MetforminLow dose temozolomide+metformin for 24 weeks | Drug | Temozolomide+metformin |
| Temozolomide+PlaceboLow dose temozolomide+placebo for 24 weeks | Drug | Temozolomide+placebo |
Primary outcome
Comparison of progression-free survival obtained from progression-free survival curve
Time frame: 24 weeks
Comparison of progression-free survival obtained from progression-free survival curve
5 secondary outcomes
Response Rate
Time frame: 4 weeks, 8 weeks, 16 weeks, 24 weeks thereafter every 24 weeks up to 96 weeks
Tumor control probability
Time frame: 4 weeks, 8 weeks, 16 weeks, 24 weeks thereafter every 24 weeks up to 96 weeks
6 month progression free survival
Time frame: 24 weeks
6 month overall survival
Time frame: 24 weeks
Assessment of the quality of life of cancer patients
Time frame: 4 weeks, 8 weeks, 16 weeks, 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2021.
- Derived from this study: PubMed 37278858Yoon WS, Chang JH, Kim JH, Kim YJ, Jung TY, Yoo H, Kim SH, Ko YC, Nam DH, Kim TM, Kim SH, Park SH, Lee YS, Yim HW, Hong YK, Yang SH. Efficacy and safety of metformin plus low-dose temozolomide in patients with recurrent or refractory glioblastoma: a randomized, prospective, multicenter, double-blind, controlled, phase 2 trial (KNOG-1501 study). Discov Oncol. 2023 Jun 6;14(1):90. doi: 10.1007/s12672-023-00678-3.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yong-Kil Hong, MD.,PhD. principal investigator
Seoul St. Mary's Hospital
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Temozolomide+Metformin in people with Glioblastoma, run by Yong-Kil Hong at 12 sites in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of progression-free survival obtained from progression-free survival curve (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03243851, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2021.