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

Phase 2

Completed

• Conditions: Glioblastoma
• Interventions: Drug: Temozolomide+Metformin; Drug: Temozolomide+Placebo

• Registration Number: NCT03243851
• Lead Sponsor: Yong-Kil Hong

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.

Study Timeline

• Study Start: 2016-11-21
• Study First Submitted: 2017-07-29
• Study First Submitted QC: 2017-08-04
• Study First Posted: 2017-08-09
• Primary Completion: 2020-12-31
• Study Completion: 2020-12-31
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-08
• Last Update Posted: 2021-09-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 81

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Temozolomide+metformin	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
Temozolomide+placebo	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

Primary Outcome Measures

Name	Time	Method
Comparison of progression-free survival obtained from progression-free survival curve	24 weeks	Comparison of progression-free survival obtained from progression-free survival curve

Secondary Outcome Measures

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

Trial Locations

Locations (12)

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

National Cancer Center Korea; 🇰🇷 Ilsan, Gyeonggi-Do, Korea, Republic of

Severance Hospital; 🇰🇷 Seoul, Korea, Republic of

Konkuk University Hospital; 🇰🇷 Seoul, Korea, Republic of

Saint Vincent's Hospital, Korea; 🇰🇷 Suwon-si, Korea, Republic of

Ajou University Hospital; 🇰🇷 Suwon-si, Gyeonggi-Do, Korea, Republic of

Chonnam National University Hwasun Hospital; 🇰🇷 Hwasun, Jeollanam-Do, Korea, Republic of

Seoul National University Bundang Hospital; 🇰🇷 Seongnam-si, Gyeonggi-Do, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Incheon St. Mary's Hospital; 🇰🇷 Incheon, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

Seoul St Mary's Hospital; 🇰🇷 Seoul, Korea, Republic of