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

NCT04657315 | Completed Phase 1 DMC

• 1 other identifier: CHAMC 2019-08-022
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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)

  after treatment discontinuation for approximately 1 years

• 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)

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

Secondary Outcomes (4)

• Overall Survival improvement (OS)

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

• Progression Free Survival (PFS)

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

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

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

• Clinical efficacy assessment

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

Study Arms (1)

The investigational drug into the Intratumoral administration

OTHER

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

Interventions

MSC11FCD DRUG

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

Also known as: Mesenchymal stem cells into which the suicide gene, cytosine deaminase (CD)

The investigational drug into the Intratumoral administration

Eligibility Criteria

• Age: 19 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• CHA University: lead
• Ajou University School of Medicine: collaborator

Study Sites (1)

Bundang CHA Medical Center

Seongnam, Kyunggido, 13496, South Korea

Location

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Brain Neoplasms; Neoplasms, Germ Cell and Embryonal; Central Nervous System Neoplasms

Interventions

Cytosine Deaminase

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Nucleoside Deaminases; Aminohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes

Study Officials

• Kyunggi Cho, MD,PhD

  CHA University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 1, 2020
• First Posted: December 8, 2020
• Study Start: June 24, 2020
• Primary Completion: December 22, 2022
• Study Completion: December 22, 2022
• Last Updated: January 18, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)