Trial Title:
A Phase I Clinical Study of Intratumoral Injection Oncolytic Vaccinia Virus GC001 in Patient With Advanced Solid Tumors
NCT ID:
NCT06508307
Condition:
Sarcoma
Cervical Cancer
Colon Cancer
Lung Cancer
Ovarian Cancer
Pancreatic Cancer
Hepatocellular Carcinoma
Breast Cancer
Gastric Cancer
Conditions: Official terms:
Vaccinia
Conditions: Keywords:
GC001、Oncolytic virus 、WR
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
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 Patients With Advanced Solid Tumors
Description:
The maximum number of lesions that each participant is allowed to inject at one time is
two.
Arm group label:
Part 1: Dose Escalation
Summary:
The present trial is an open, single-arm phase I clinical study aimed at assessing the
safety, tolerability, viral distribution and shedding patterns, pharmacodynamics,
immunogenicity, and antitumor efficacy of GC001 oncolytic virus injection in patients
with advanced solid tumors following a single administration.
Detailed description:
The main objective of this study 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 advanced solid tumors.
The ongoing trial is structured as an open, single-arm Phase I clinical study. 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 an
anticipated enrollment ranging from 21 to 36 eligible individuals. 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 investigation 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 solid
tumors. These objectives are integral to understanding the broader impact and potential
of the treatment in this patient population.
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
To be eligible for participation in this study, individuals must meet the following
criteria:
1. Fully comprehend the purpose, nature, methods, and potential adverse effects of the
trial, volunteer as a participant, and provide informed consent by signing the form
prior to undergoing any procedures.
2. Be male or female patients aged 18 to 75 years (including those with borderline age
values).
3. Patients with advanced solid tumors, including but not limited to: colorectal
cancer, lung cancer, ovarian cancer, cervical cancer, etc., that have been
histologically or cytologically 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).
4. Possess at least one extracranial measurable lesion (as determined by a CT scan or
MRI conducted no more than 4 weeks before signing the informed consent form) that is
suitable for intratumoral injection based on RECIST v1.1 criteria.
5. Have an Eastern Cooperative Oncology Group (ECOG) physical status score of 0 or 1.
6. Be expected to survive for at least 3 months.
7. Within 7 days prior to receiving the first dose of treatment, patients must meet the
following organ function and bone marrow reserve:
1. Hematology: platelets (PLT) ≥ 80 × 109/L, neutrophil count (ANC) ≥ 1.5 × 109/L,
and hemoglobin ≥ 9 g/dL (without having received adjuvants like EPO, G-CSF, or
GM-CSF in the 14 days leading up to the first dose, and not having received a
blood transfusion for at least 7 days);
2. Coagulation function: INR ≤ 1.2, APTT ≤ 1.2 × ULN (upper limit of normal), PT ≤
1.2 × ULN;
3. Hepatic function: total bilirubin ≤ 1.5
4. × ULN (patients with Gilbert syndrome may be enrolled with a total bilirubin ≤
3 × ULN), AST and ALT ≤ 3 × ULN (or ≤ 5 × ULN in the presence of hepatic
metastases);
5. Renal function: serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50
mL/min (according to the Cockcroft-Gault formula, see Appendix 2 for details);
6. Cardiac function: QT interval (QTcF) ≤ 470 ms in female and ≤ 450 ms in male.
8. Ability to effectively communicate with the investigator and comprehend and adhere
to the requirements of the study.
Exclusion Criteria:
1. 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.
2. Females of childbearing age who have a positive pregnancy test or are lactating.
3. Individuals with allergies (defined as ≥2 drug allergies) or hypersensitivity to
similar products or excipients.
4. Those who have received smallpox vaccination and experienced severe systemic
reactions or side effects.
5. Patients who have previously received lysosomal virus, stem cell, or gene therapy
products.
6. 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).
7. 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;
Individuals using small molecule targeted agents with antitumor effects within 14
days prior to the first administration of the drug or within 5 times the half-life
of the drug (whichever is longer); Individuals using herbal medicines with antitumor
effects within 14 days prior to the first administration of the drug.
8. Individuals who have undergone surgery or interventional therapy (excluding tumor
biopsy, puncture, etc.), or have unhealed wounds, ulcers, or fractures within 28
days prior to the first dose.
9. Individuals who have been treated with systemic corticosteroids (at a dose
equivalent to >10 mg prednisone/day) or other immunosuppressive medications within
28 days prior to the first dose, or who are currently taking antiviral medications
(such as ribavirin, rifampin, imatinib, etc.), 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;
3. patients with hepatitis B who are stable while receiving antiviral medications.
10. Patients with clinically symptomatic CNS metastases or poorly controlled CNS
metastases despite treatment (patients who have been stable for more than 4 weeks by
MRI/CT without requiring steroidal medications or other CNS-targeted treatments for
at least 4 weeks) may be eligible for enrollment.
11. Individuals with clinically significant or rapidly accumulating ascites, pericardial
and/or pleural effusions.
12. A history of severe cardiovascular disease, including but not limited to:
1. evere cardiac rhythm or conduction abnormalities, such as ventricular
arrhythmias requiring medical intervention, II-III degree atrioventricular
block, etc;
2. According to the standards of the New York Heart Association (NYHA),
individuals with grade III-IV heart failure;
3. Recent cardiovascular events such as acute coronary syndrome, congestive heart
failure, aortic dissection, stroke, cerebrovascular malformation, or other
Grade 3 or higher events within the past 6 months prior to the first
administration;
4. Uncontrolled hypertension despite standard antihypertensive therapy, with blood
pressure persistently above systolic blood pressure < 160 mmHg and diastolic
blood pressure < 100 mmHg.
13. 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.
14. Those with a history of severe hemoptysis。
15. Adverse effects from prior antineoplastic therapy that have not recovered to a CTCAE
v5.0 grade rating of ≤ 1 (excluding non-risky toxicities like alopecia).
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.
18. Individuals with a history of exfoliative skin conditions requiring systemic therapy
(e.g., eczema or atopic dermatitis) are also excluded。
19. Persons who are positive for human immunodeficiency virus (HIV) antibodies.
20. 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.
21. Male and female patients who refuse to use an appropriate method of contraception,
(such as the simultaneous use of spermicides, barrier contraceptives, and/or
intrauterine contraceptives, as outlined in Appendix 1) throughout the study period
and during the safety follow-up period are excluded.
22. Patients with documented psychiatric illnesses or disorders that may impact
adherence to the trial protocol.
23. Patients with malignant tumors that may require antitumor therapy other than the
investigational drug GC001.
24. Patients who, as determined by the investigator, are unsuitable for participation in
the study, including those with tumors surrounding major vascular structures such as
the carotid arteries, tumors adjacent to critical neurovascular structures, or
airways, or tumors in locations that present a high risk of adverse events or are
unsuitable for intratumoral injections.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Henan Cancer Hospital
Address:
City:
Zhengzhou
Zip:
450000
Country:
China
Status:
Recruiting
Contact:
Last name:
MO guoyu
Phone:
13710803863
Email:
morlon_pla@126.com
Start date:
April 26, 2023
Completion date:
June 2025
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/NCT06508307
