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

NCT ID: NCT03243851

Last Updated: 2021-09-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

81 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-11-21

Study Completion Date

2020-12-31

Brief Summary

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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

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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

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Glioblastoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Arm 1 : Low dose temozolomide+metformin Arm 2 : Low dose temozolomide+placebo
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Double blinded

Study Groups

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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 :

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

Group Type EXPERIMENTAL

Temozolomide+Metformin

Intervention Type DRUG

Low dose temozolomide+metformin for 24 weeks

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:

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

Group Type PLACEBO_COMPARATOR

Temozolomide+Placebo

Intervention Type DRUG

Low dose temozolomide+placebo for 24 weeks

Interventions

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Temozolomide+Metformin

Low dose temozolomide+metformin for 24 weeks

Intervention Type DRUG

Temozolomide+Placebo

Low dose temozolomide+placebo for 24 weeks

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

19 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Saint Vincent's Hospital, Korea

OTHER

Sponsor Role collaborator

Incheon St.Mary's Hospital

OTHER

Sponsor Role collaborator

National Cancer Center, Korea

OTHER_GOV

Sponsor Role collaborator

Konkuk University Hospital

OTHER

Sponsor Role collaborator

Seoul National University Bundang Hospital

OTHER

Sponsor Role collaborator

Samsung Medical Center

OTHER

Sponsor Role collaborator

Seoul National University Hospital

OTHER

Sponsor Role collaborator

Asan Medical Center

OTHER

Sponsor Role collaborator

Ajou University School of Medicine

OTHER

Sponsor Role collaborator

Severance Hospital

OTHER

Sponsor Role collaborator

Chonnam National University Hospital

OTHER

Sponsor Role collaborator

Seoul St. Mary's Hospital

OTHER

Sponsor Role collaborator

Yong-Kil Hong

OTHER

Sponsor Role lead

Responsible Party

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Yong-Kil Hong

MD., PhD.

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Yong-Kil Hong, MD.,PhD.

Role: PRINCIPAL_INVESTIGATOR

Seoul St. Mary's Hospital

Locations

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National Cancer Center Korea

Ilsan, Gyeonggi-do, South Korea

Site Status

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Site Status

Ajou University Hospital

Suwon, Gyeonggi-do, South Korea

Site Status

Chonnam National University Hwasun Hospital

Hwasun, Jeollanam-do, South Korea

Site Status

Incheon St. Mary's Hospital

Incheon, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Severance Hospital

Seoul, , South Korea

Site Status

Konkuk University Hospital

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Seoul St Mary's Hospital

Seoul, , South Korea

Site Status

Saint Vincent's Hospital, Korea

Suwon, , South Korea

Site Status

Countries

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South Korea

References

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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.

Reference Type DERIVED
PMID: 37278858 (View on PubMed)

Other Identifiers

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KNOG-1501

Identifier Type: -

Identifier Source: org_study_id

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