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

Primary Purpose

Glioblastoma, Adult Gliosarcoma, Neoplasms, Brain

Status

Completed

Phase

Phase 1

Locations

Korea, Republic of

Study Type

Interventional

Intervention

MSC11FCD

About this trial

This is an interventional treatment trial for Glioblastoma focused on measuring Glioblastoma, Mesenchymal stem cells, Brain Tumor, Neoplasms, Germ Cell, Flucytosine, Central Nervous System Neoplasms

Eligibility Criteria

19 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Bundang CHA Medical Center

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

The investigational drug into the Intratumoral administration

Arm Description

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

Outcomes

Primary Outcome Measures

Maximum tolerated dose (MTD)

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

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)

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)

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

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

Karnofsky performance status (KPS) assessment

Full Information

NCT ID

NCT04657315

First Posted

November 1, 2020

Last Updated

January 14, 2023

Sponsor

CHA University

Collaborators

Ajou University School of Medicine

1. Study Identification

Unique Protocol Identification Number

NCT04657315

Brief Title

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

Acronym

MSC11FCD-GBM

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Completed

Study Start Date

June 24, 2020 (Actual)

Primary Completion Date

December 22, 2022 (Actual)

Study Completion Date

December 22, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

CHA University

Collaborators

Ajou University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

Detailed Description

Not Provided

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma, Adult Gliosarcoma, Neoplasms, Brain, Neoplasms, Germ Cell and Embryonal, Recurrent Glioblastoma

Keywords

Glioblastoma, Mesenchymal stem cells, Brain Tumor, Neoplasms, Germ Cell, Flucytosine, Central Nervous System Neoplasms

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

The investigational drug into the Intratumoral administration

Arm Type

Other

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

MSC11FCD

Other Intervention Name(s)

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

Intervention Description

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

Primary Outcome Measure Information:

Title

Maximum tolerated dose (MTD)

Description

Time Frame

after treatment discontinuation for approximately 1 years

Title

Number Of Adverse Events related to the treatment

Description

Time Frame

Baseline, Day0, 1 month, 3 months, 6 months, 12 months

Secondary Outcome Measure Information:

Title

Overall Survival improvement (OS)

Description

OS is defined as the time from the date of MSC injection to the date of death due to any cause.

Time Frame

Study entry through the end of the study, up to 12 months

Title

Progression Free Survival (PFS)

Description

The progress-free survival analysis shall be based on the RANO criteria.

Time Frame

Study entry through the end of the study, up to 12 months

Title

Tumor assessment in regard to the investigational drug based on the RANO criteria

Description

Time Frame

At Baseline, 1month, 3months, 6months, 12months

Title

Clinical efficacy assessment

Description

Karnofsky performance status (KPS) assessment

Time Frame

At Baseline, 1month, 3months, 6months, 12months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

19 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kyunggi Cho, MD,PhD

Organizational Affiliation

CHA University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Bundang CHA Medical Center

City

Seongnam

State/Province

Kyunggido

ZIP/Postal Code

13496

Country

Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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