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

NCT03243851 | Completed Phase 2 DMC

• 1 other identifier: KNOG-1501
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 12

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

Conditions

Glioblastoma

Keywords

Glioblastoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Response Rate

  4 weeks, 8 weeks, 16 weeks, 24 weeks thereafter every 24 weeks up to 96 weeks

• Tumor control probability

  4 weeks, 8 weeks, 16 weeks, 24 weeks thereafter every 24 weeks up to 96 weeks

• 6 month progression free survival

  24 weeks

• 6 month overall survival

  24 weeks

• Assessment of the quality of life of cancer patients

  4 weeks, 8 weeks, 16 weeks, 24 weeks

Study Arms (2)

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

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

Drug: Temozolomide+Placebo

Interventions

Temozolomide+Metformin DRUG

Low dose temozolomide+metformin for 24 weeks

Temozolomide+metformin

Temozolomide+Placebo DRUG

Low dose temozolomide+placebo for 24 weeks

Temozolomide+placebo

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (12)

National Cancer Center Korea

Ilsan, Gyeonggi-do, 10408, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Ajou University Hospital

Suwon, Gyeonggi-do, 16499, South Korea

Location

Chonnam National University Hwasun Hospital

Hwasun, Jeollanam-do, 58128, South Korea

Location

Incheon St. Mary's Hospital

Incheon, 21431, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Konkuk University Hospital

Seoul, 05030, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Seoul St Mary's Hospital

Seoul, 06591, South Korea

Location

Saint Vincent's Hospital, Korea

Suwon, 16247, South Korea

Location

Related Publications (1)

• 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.

  PMID: 37278858 DERIVED

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Yong-Kil Hong, MD.,PhD.

  Seoul St. Mary's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD., PhD.

Model Details: Arm 1 : Low dose temozolomide+metformin Arm 2 : Low dose temozolomide+placebo

Study Record Dates

• First Submitted: July 29, 2017
• First Posted: August 9, 2017
• Study Start: November 21, 2016
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: September 9, 2021

Record last verified: 2021-09

Locations

KR (12)