Trial Title:
A Phase I Clinical Study of Intratumoral Injection GC001 in Patient With Recurrent or Progressive Gliomas
NCT ID:
NCT06660056
Condition:
High-grade Gliomas
Conditions: Official terms:
Glioma
Conditions: Keywords:
GC001、Oncolytic virus 、WR、high-grade gliomas
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
3+3
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
A Phase I Clinical Study of Intratumoral Injection Oncolytic Vaccinia Virus GC001 in Patient With Recurrent or Progressive Gliomas of the Brain
Description:
Use of Ommaya capsules
Arm group label:
Part 1: Dose Escalation
Arm group label:
Part 2:metrological amplification stage
Summary:
A Phase I Study Evaluating the Safety, Tolerability, Biodistribution and Shedding of the
Virus, Pharmacodynamics, Immunogenicity, and Antitumor Activity of GC001 Oncolytic
Vaccinia Virus Injection in Patient With Recurrent or Progressive Gliomas .
Detailed description:
The ongoing trial is structured as an open, single-arm Phase I clinical study consisting
of dose-escalation and dose-expansion.
The main objective of dose-escalation is:
To evaluate the safety and tolerability i.e. dose limiting toxicity (DLT), maximum
tolerated dose (MTD) or maximum administered dose (MFD) of GC001 injection in patients
with with recurrent or progressive gliomas,and will be determining the recommended phase
II dose(PR2D).
The initial phase of the study, Part I, utilizes a 3+3 design to meticulously evaluate
the escalation of the dose of GC001. The total enrollment of participants will be
determined by the observed toxicity levels and the extent of dose cohorts explored, with
a maximum enrollment of 42 cases. A critical 28-day period post-administration has been
established for the observation of dose-limiting toxicities (DLTs) to ensure participant
safety. It is essential to maintain this standardized 28-day observation window for all
enrolled groups to uphold the highest safety standards.
The secondary aims of this dose-escalation are to assess the biodistribution and shedding
of the virus, the pharmacodynamic characteristics, immunogenicity, and the initial
antitumor efficacy of the GC001 injection in patients suffering from advanced with
recurrent or progressive gliomas.
Following the completion of the DLT assessment for all participants within each dose
cohort, the SMC may decide whether to proceed with dose escalation, explore
intermediate/higher doses, or terminate the dose escalation study based on the data
obtained on safety, tolerability, biodistribution, and shedding of the virus (if any),
pharmacodynamics (if any), immunogenicity (if any), and antitumor activity (if any). The
SMC may also decide to adjust doses, administration schedules, and the time of
biospecimen collection.
To further evaluate the safety and preliminary antitumor activity of GC001 Oncolytic
Vaccinia Virus Injection in the treatment of patients with With recurrent or progressive
gliomas during the dose-expansion phase.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
To be eligible for participation in this study, individuals must meet the following
criteria:
1. Subjects must be able to comprehend and voluntarily sign written informed consent,
which includes requirements related to study sample collection.
2. Able to communicate with researchers; Understand and comply with the requirements of
the study; Voluntary and able to complete study procedures and follow-up
examinations.
3. Be male or female patients aged 18 (including those with borderline age values).
4. Patients with recurrent or progressive high-grade gliomas (WHO grade III-IV) that
have been histopathologically or molecularly diagnosed and for which there is either
no current standard of care or the standard treatment has proven ineffective
(progression of the disease after treatment or intolerance of treatment).
5. At least 1 intracranial measurable lesion according to RANO criteria (well-defined
enhancing lesion detected on MRI, diameter >10 mm).
6. Patient's willingness to undergo surgical maneuvers related to placement of the
Ommaya capsule.
7. Karnofsky functional status ≥ 60.
8. Be expected to survive for at least 3 months.
9. No serious hematologic (no adjuncts such as EPO, G-CSF, or GM-CSF within 14 days
prior to the first dose and no blood transfusions for at least 7 days), hepatic, or
renal function abnormalities consistent with the following laboratory test results:
systems Laboratory test values routine blood test Absolute neutrophil count（ANC）
≥1.5×109/L blood platelet（PLT） ≥100×109/L hemoglobin（HGB） ≥90g/L gallbladder serum
creatinine（Cr） ≤1.5×Upper limit of normal range（ULN） creatinine clearance（Ccr）（To be
calculated only if creatinine > 1.5 x ULN） ≥50mL/min（Based on the Cockcroft-Gault
formula） liver total bilirubin（TBIL） ≤1.5×ULN glutamic pyruvic transaminase（ALT）
aspartate transaminase（AST） ≤2.5×ULN Alkaline phosphatase（ALP） ≤2.5×ULN coagulation
International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5×ULN Partially
activated thromboplastin time（APTT） ≤1.5×ULN 10.Male or female subjects of childbearing
potential use effective contraception during treatment and for 6 months after dosing.
Exclusion Criteria:
1. Inability to perform an MRI for any reason.
2. focal point under the curtain.
3. Prior history of encephalitis, multiple sclerosis, or other central nervous system
infection (unless resolved).
4. Patients with a previous diagnosis of any other malignancy within 5 years prior to
the first dose, except for malignancies with a low risk of metastasis and risk of
death (5-year survival > 90%), such as adequately treated basal cell or squamous
cell skin cancer, cervical carcinoma in situ, and other carcinomas in situ.
5. Females of childbearing age who have a positive pregnancy test or are lactating.
6. Individuals with allergies (defined as ≥2 drug allergies) or hypersensitivity to
similar products or excipients.
7. Those who have received smallpox vaccination and experienced severe systemic
reactions or side effects.
8. Patients who have previously received lysosomal virus, stem cell, or gene therapy
products.
9. Individuals using other investigational drugs or participating in clinical trials of
other drugs within 28 days prior to the first dose (except for those who did not
receive the test drug).
10. Those who have undergone antitumor therapy, including radiation therapy (except
palliative radiotherapy), chemotherapy, biotherapy, endocrine therapy, and
immunotherapy within 28 days prior to the first administration of the drug.
11. Individuals who have undergone surgery or interventional therapy (excluding tumor
biopsy, puncture, Ommaya capsule etc.).
12. Individuals who have been treated with systemic corticosteroids (at a dose
equivalent to >10 mg dexamethasone /day) or other immunosuppressive medications
within 28 days prior to the first dose, or who are currently taking antiviral
medications (Mainly sensitive to poxviruses), enrollment is permitted under the
following cases:
1. short-term (≤7 days) use of corticosteroids for prophylaxis or treatment of
non-autoimmune allergic diseases is permitted;
2. the use of topical topical or inhaled glucocorticoids is permitted;.
13. A history of severe cardiovascular disease, including but not limited to:
1. A history of severe cardiac rhythm or conduction abnormalities, such as
ventricular arrhythmias, degree II-III AV block requiring clinical
intervention;
2. Acute coronary syndrome, congestive heart failure, aortic coarctation, stroke,
or other grade or greater cardiovascular event within 6 months prior to the
first dose;
3. New York Heart Association (NYHA) > Class II heart failure or left ventricular
ejection fraction (LVEF) <50%; heart rate-corrected baseline QTcF intervals
>450msec (men) and >470msec (women) using the Fridericia formula; any factor
that increases the risk of QTc prolongation or the risk of cardiac arrhythmias,
such as heart failure, hypokalemia , congenital long QT syndrome, family
history of long QT syndrome, or use of any concomitant medication known to
prolong the QT interval；
4. Clinically uncontrolled hypertension (blood pressure uncontrolled at < 160 mmHg
systolic and < 100 mmHg diastolic after standard antihypertensive treatment).
14. Recent Grade 3 or greater bleeding event within 6 months prior to the first use of
study drug, or who have current > Grade 2 bleeding, or hemangioma/vascular
malformation, or tumor stroke, tumor invasion of a blood vessel, or active peptic
ulcer, or esophageal varices judged by the investigator to be at significant risk
for bleeding.
15. Those with a history of severe hemoptysis.
16. Patients with uncontrolled or severe diseases, including but not limited to
persistent or active infections requiring antibiotic therapy.
17. .Subjects with active or prior history of autoimmune diseases with potential for
recurrence (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory
bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis,
glomerulonephritis, etc.) or at high risk (e.g., patients who have undergone organ
transplantation requiring immunosuppressive therapy) are not eligible for
enrollment. However, enrollment is permitted for subjects with:
1. type 1 diabetes mellitus that is stabilized on a fixed dose of insulin;
2. autoimmune hypothyroidism or Hashimoto's thyroiditis that requires only hormone
replacement therapy；
3. Individuals with a history of exfoliative skin conditions requiring systemic
therapy (e.g., eczema or atopic dermatitis) are also excluded.
18. Persons who are positive for human immunodeficiency virus (HIV) antibodies.
19. Persons who have active hepatitis B (HBV)/hepatitis C (HCV) infection are not
eligible for enrollment. However, subjects with a previous history of hepatitis C
but negative HCV RNA at screening may be enrolled, and those who are HBsAg positive
but have HBV DNA <500 IU/ml or below the lower limit of detection at the study
center may also be enrolled. Subjects with primary liver cancer and HBV DNA <1000
IU/ml may be enrolled as well.
20. Patients with documented psychiatric illnesses or disorders that may impact
adherence to the trial protocol.
21. Patients with malignant tumors that may require antitumor therapy other than the
investigational drug GC001.
22. Patients who, as determined by the investigator, are unsuitable for participation in
the study.
-
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Beijing Tiantan Hospital,Capital Medical University
Address:
City:
Beijing
Zip:
100000
Country:
China
Status:
Recruiting
Contact:
Last name:
MO guoyu
Phone:
13710803863
Email:
morlon_pla@126.com
Start date:
October 8, 2024
Completion date:
August 8, 2026
Lead sponsor:
Agency:
GONGCHU Biotechnology Co., Ltd
Agency class:
Other
Source:
GONGCHU Biotechnology Co., Ltd
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06660056
