MSC11FCD-GBM: Evaluation of Maximum Tolerated Dose, Safety and Efficiency of MSC11FCD Therapy to Recurrent Glioblastoma Patients

Sponsor

CHA University (Other)

Overall Status

Enrolling by invitation

CT.gov ID

NCT04657315

Collaborator

Ajou University School of Medicine (Other)

Enrollment

Location

Arm

30.2

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase I trial evaluating the maximum tolerated dose, safety and efficiency of Mesenchymal stem cells into which the suicide gene, cytosine deaminase (CD), injected into the resection cavity of patients with recurrent glioblastoma.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma Adult Gliosarcoma Neoplasms, Brain Neoplasms, Germ Cell and Embryonal Recurrent Glioblastoma	Drug: MSC11FCD	Phase 1/Phase 2

Detailed Description

Not Provided

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Investigator-initiated and Open-labeled Clinical Trial for Evaluation of Maximum Tolerated Dose, Safety and Efficiency of MSC11FCD Therapy to Recurrent Glioblastoma Patients

Actual Study Start Date :

Jun 24, 2020

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Other: The investigational drug into the Intratumoral administration The investigational drug in the amount of 1x10^7, 3x10^7cells per dose into the tumor or the tumor removal site using a syringe during surgery	Drug: MSC11FCD Administration period: Single dose Route of administration: Intratumoral administration Dose: 1x10^7, 3x10^7cells/dose Summary: Administer the investigational drug in the amount of 1x107, 3x107cells per dose into the tumor or the tumor removal site using a syringe during surgery. Concomitant drug: 5-Flucytosine (prodrug) Dose: 150mg/kg/day Directions: Administration period and directions: Administer 150m of 5-Flucytosine per kilogram of body weight every 6 hours for a total of 4 times a day (QID) for a duration of 7 days after surgery. Route of administration: Oral administration Other Names: Mesenchymal stem cells into which the suicide gene, cytosine deaminase (CD)

Arm

Intervention/Treatment

Other: The investigational drug into the Intratumoral administration

The investigational drug in the amount of 1x10^7, 3x10^7cells per dose into the tumor or the tumor removal site using a syringe during surgery

Drug: MSC11FCD

Administration period: Single dose Route of administration: Intratumoral administration Dose: 1x10^7, 3x10^7cells/dose Summary: Administer the investigational drug in the amount of 1x107, 3x107cells per dose into the tumor or the tumor removal site using a syringe during surgery. Concomitant drug: 5-Flucytosine (prodrug) Dose: 150mg/kg/day Directions: Administration period and directions: Administer 150m of 5-Flucytosine per kilogram of body weight every 6 hours for a total of 4 times a day (QID) for a duration of 7 days after surgery. Route of administration: Oral administration

Other Names:

Mesenchymal stem cells into which the suicide gene, cytosine deaminase (CD)

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose (MTD) [after treatment discontinuation for approximately 1 years]
Assessment of the maximum tolerated dose based on the 3+3 method Blood concentrations of 5-FC and 5-FU(Day 1, Day 3, Day 7) MSC11FCD concentrations (MSCCD detection) (Day 0, 3months, 6months, 12months)
Number Of Adverse Events related to the treatment [Baseline, Day0, 1 month, 3 months, 6 months, 12 months]
Evaluate the number of adverse event related to the treatment according to CTCAE V4.0 during the trial (including clinically significant changes in physical examination, radiographic images, safety lab tests, vital signs)

Secondary Outcome Measures

Overall Survival improvement (OS) [Study entry through the end of the study, up to 12 months]
OS is defined as the time from the date of MSC injection to the date of death due to any cause.
Progression Free Survival (PFS) [Study entry through the end of the study, up to 12 months]
The progress-free survival analysis shall be based on the RANO criteria.
Tumor assessment in regard to the investigational drug based on the RANO criteria [At Baseline, 1month, 3months, 6months, 12months]
Assess the treatment groups participating in this clinical trial based on the RANO criteria. Compare and present the disease control rates by calculating the ratio of the number of subjects responding to treatment (complete response: CR, partial response: PR, stable disease: SD) among the treatment groups and control group assessed based on the RANO criteria.
Clinical efficacy assessment [At Baseline, 1month, 3months, 6months, 12months]
Karnofsky performance status (KPS) assessment

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients aged 19 to 70
Patients diagnosed with recurrent glioblastoma based on medical imaging after receiving standard therapy for glioblastoma
Patients scheduled to undergo surgical treatment for recurrent glioblastoma
Patients diagnosed with recurrent glioblastoma based on medical imaging (MRI: conventional, diffusion, perfusion, spectroscopy) and confirmed to have tumor cells during surgery based on frozen biopsy
Patients whose expected survival period is at least 3 months
Patients who have not received any other types of immunotherapy
Patients who have been given a sufficient explanation of the purpose and details of the clinical trial and the characteristics of the investigational drug from an investigator and who signed the consent form or had a legal guardian or representative sign the consent form prior to the beginning of this clinical trial
Patients who have waited for at least four weeks after treatment using cytotoxic drugs in order to eliminate the possibility of impact and effects from other therapeutic agents (23 days after the last administration in case of undergoing standard therapy using temozolomide)

Exclusion Criteria:

Patients who have primary glioblastoma
Patients with dihydropyrimidine dehydrogenase (DPD) deficiency
Patients who cannot undergo a contrast (gadolinium) enhanced MRI scan due to a certain condition (pacemaker, etc.) or cannot undergo an MRI scan according to the clinical trial schedule due to any other reasons
Patients to whom Gliadel water was applied during surgery
Patients who are deemed to have a serious dysfunction in any of the major organs (liver, kidneys, bone marrow, lungs, heart) by the investigator
Patents who have other types of malignant tumor aside from glioblastoma or who have had malignant tumor in the past 5 years
Patients who uncontrolled hypotension or hypertension
Diabetic patients who are currently receiving insulin therapy or who need insulin therapy
Patients who are deemed to have a serious infectious disease by the investigator: sepsis, hepatitis A, hepatitis B or hepatitis C (in the case of hepatitis B and C viruses, however, carriers may be enrolled at the investigator's discretion) or tested positive in a serological test for the human immunodeficiency virus (HIV)
Karnofsky Performance Scale < 60
Patients with an autoimmune disease affecting the central nervous system (multiple sclerosis, myasthenia gravis, acute disseminated encephalomyelitis, etc.)
Patients with a history of allergic reactions to flucytosine (5-FC) and/or its excipients or 5-fluorouracil (5-FU)
Pregnant or lactating women or patients who plan on getting pregnant during the clinical trial or refuses to choose an appropriate method of contraception
Patients who have participated in a different clinical trial no more than 30 days prior to registering for this clinical trial
Patients who are deemed to be unfit for this clinical trial by the investigator