Clinical trial NCT03243851: Study on Low Dose Temozolomide Plus Metformin or Placebo in Patient With Recurrent or Refractory Glioblastoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioblastoma
Keywords: Glioblastoma
Lead sponsor: Seoul St. Mary's Hospital
Sponsor class: OTHER
Collaborators: name: Saint Vincent's Hospital, Korea
name: Incheon St.Mary's Hospital
name: National Cancer Center, Korea
name: Konkuk University Hospital
name: Seoul National University Bundang Hospital
name: Samsung Medical Center
name: Seoul National University Hospital
name: Asan Medical Center
name: Ajou University School of Medicine
name: Severance Hospital
name: Chonnam National University Hospital
name: Seoul St. Mary's Hospital
First posted: 2017-08-09
Enrollment: 81
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Arm 1 : Low dose temozolomide+metformin Arm 2 : Low dose temozolomide+placebo
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Comparison of progression-free survival obtained from progression-free survival curve
timeFrame: 24 weeks
Secondary outcomes:
measure: Response Rate
timeFrame: 4 weeks, 8 weeks, 16 weeks, 24 weeks thereafter every 24 weeks up to 96 weeks
measure: Tumor control probability
timeFrame: 4 weeks, 8 weeks, 16 weeks, 24 weeks thereafter every 24 weeks up to 96 weeks
measure: 6 month progression free survival
timeFrame: 24 weeks
measure: 6 month overall survival
timeFrame: 24 weeks
measure: Assessment of the quality of life of cancer patients
timeFrame: 4 weeks, 8 weeks, 16 weeks, 24 weeks
Other outcomes:
Locations:
city: Ilsan
country: Korea, Republic of
facility: National Cancer Center Korea
state: Gyeonggi-Do
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-Do
city: Suwon-si
country: Korea, Republic of
facility: Ajou University Hospital
state: Gyeonggi-Do
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
state: Jeollanam-Do
city: Incheon
country: Korea, Republic of
facility: Incheon St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Konkuk University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul St Mary's Hospital
city: Suwon-si
country: Korea, Republic of
facility: Saint Vincent's Hospital, Korea
Study officials:
affiliation: Seoul St. Mary's Hospital
name: Yong-Kil Hong, MD.,PhD.
role: PRINCIPAL_INVESTIGATOR
References: