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

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

Sponsors

Lead Sponsor: Yong-Kil Hong

Collaborator: 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

Source Seoul St. Mary's Hospital
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.

Overall Status Recruiting
Start Date November 21, 2016
Completion Date December 31, 2019
Primary Completion Date December 31, 2019
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Comparison of progression-free survival obtained from progression-free survival curve 24 weeks
Secondary Outcome
Measure Time Frame
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
Enrollment 108
Condition
Intervention

Intervention Type: Drug

Intervention Name: Temozolomide+Metformin

Description: Low dose temozolomide+metformin for 24 weeks

Arm Group Label: Temozolomide+metformin

Intervention Type: Drug

Intervention Name: Temozolomide+Placebo

Description: Low dose temozolomide+placebo for 24 weeks

Arm Group Label: Temozolomide+placebo

Eligibility

Criteria:

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.

Gender: All

Minimum Age: 19 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Yong-Kil Hong, MD.,PhD. Principal Investigator Seoul St. Mary's Hospital
Overall Contact

Last Name: Yong-Kil Hong, MD., PhD.

Phone: +82-2-2258-2101

Email: [email protected]

Location
Facility: Status: Contact:
National Cancer Center Korea | Ilsan, Gyeonggi-Do, 10408, Korea, Republic of Recruiting Heon Yoo, MD., PhD. +82-31-920-1249 [email protected]
Seoul National University Bundang Hospital | Seongnam-si, Gyeonggi-Do, 13620, Korea, Republic of Recruiting Yu Jung Kim, MD., PhD. +82-31-787-8210 [email protected]
Ajou University Hospital | Suwon-si, Gyeonggi-Do, 16499, Korea, Republic of Recruiting Se Hyuk Kim, MD., PhD. +82-31-219-3559 [email protected]
Chonnam National University Hwasun Hospital | Hwasun, Jeollanam-Do, 58128, Korea, Republic of Recruiting Shin Jung, MD., PhD. +82-2-379-8954 [email protected]
Incheon St. Mary's Hospital | Incheon, 21431, Korea, Republic of Recruiting Dong Sup Chung, MD., PhD. +82-32-280-5876 [email protected]
Seoul National University Hospital | Seoul, 03080, Korea, Republic of Recruiting Tae Min Kim, MD., PhD. +82-2-2072-1672 [email protected]
Severance Hospital | Seoul, 03722, Korea, Republic of Recruiting Jong Hee Chang, MD., PhD. +82-2-2228-2162 [email protected]
Konkuk University Hospital | Seoul, 05030, Korea, Republic of Recruiting Young Cho Koh, MD., PhD. +82-2-2030-7622 [email protected]
Asan Medical Center | Seoul, 05505, Korea, Republic of Recruiting Jeong Hoon Kim, MD., PhD. +82-2-3010-3559 [email protected]
Samsung Medical Center | Seoul, 06351, Korea, Republic of Recruiting Do Hyun Nam, MD., PhD. +82-2-3410-3497 [email protected]
Seoul St Mary's Hospital | Seoul, 06591, Korea, Republic of Recruiting Yong-Kil Hong, MD., PhD. +82-2-2258-2101 [email protected]
Saint Vincent's Hospital, Korea | Suwon-si, 16247, Korea, Republic of Recruiting Seung Ho Yang, MD., PhD. +82-31-249-8304 [email protected]
Location Countries

Korea, Republic of

Verification Date

April 2019

Responsible Party

Type: Sponsor-Investigator

Investigator Affiliation: Seoul St. Mary's Hospital

Investigator Full Name: Yong-Kil Hong

Investigator Title: MD., PhD.

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Temozolomide+metformin

Type: Experimental

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

Label: Temozolomide+placebo

Type: Placebo Comparator

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

Acronym METT
Patient Data Undecided
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Intervention Model Description: Arm 1 : Low dose temozolomide+metformin Arm 2 : Low dose temozolomide+placebo

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description: Double blinded

Source: ClinicalTrials.gov