Trial Title:
A Clinical Study on Evaluating Intravenous Administration of IDOV-SAFE
NCT ID:
NCT06380309
Condition:
Advanced Malignant Solid Tumor of Digestive System
Conditions: Official terms:
Neoplasms
Digestive System Neoplasms
Gastrointestinal Neoplasms
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Single (Investigator)
Intervention:
Intervention type:
Biological
Intervention name:
IDOV-SAFE
Description:
Intravenous injection of oncolytic virus every 3 weeks until tumor progression
Arm group label:
1E10 PFU of oncolytic virus
Arm group label:
1E9 PFU of oncolytic virus
Arm group label:
3E10 PFU of oncolytic virus
Arm group label:
3E9 PFU of oncolytic virus
Summary:
Subjects were inoperable Chinese patients with histologically or cytologically confirmed
advanced malignant solid tumors (mainly focusing on MSS type colorectal cancer) who had
failed standard systemic therapy.
In the first stage, each subject was given three doses on day 1, day 3 and day 5, and was
divided into 4 dose groups, including 1 subject in the first dose group and 3-6 subjects
in each of the last three dose groups. The second stage was the dose extension stage,
with 2 dose groups, at least 10 subjects were enrolled in the selected group, and the
administration method was the same as that of the first stage. There were about 20-60
cases in the two stages.
Detailed description:
The therapeutic dose for mice was 1E8PFU, and the maximum starting dose for humans was
2.67E9 PFU based on the Guidelines for Estimating the Maximum Recommended Starting Dose
for the First Clinical Trial of Healthy Adult Volunteers.
Dose escalation phase:
At this stage, we plan to enroll about 10-19 patients with advanced malignant solid
tumors confirmed by histology or cytology after failure of standard treatment or without
standard treatment in China for intravenous administration of IDOV-SAFETM. This stage was
divided into two cohorts: Cohort 1: patients with MSS type colorectal cancer were
included; Cohort 2: patients with digestive system tumors such as cholangiocarcinoma,
gastric cancer, esophageal cancer, and liver cancer were included (about 6 to 13 subjects
in cohort 1 and 4 to 6 subjects in cohort 2 were included preferentially, ensuring that 1
to 2 subjects for each tumor species were included).
This phase consisted of four dose groups: 1E9 PFU, 3E10 PFU, 1E10 PFU and 3E10 PFU. The
first dose group included 1 subject, and the other dose groups were increased by "3+3",
with 3-6 subjects in each group. All subjects in each dose group may be progressively
moved to the next dose group after completing a 28-day safety assessment.
The dose escalation or setting may be adjusted as determined by the Safety Committee
(SMC).
Dose expansion phase:
In the dose expansion stage, the previous dose or an intermediate dose of MTD and the
subsequent clinical dosage to be used were selected to carry out the expansion test, and
1 to 2 tumor species were selected for expansion according to the efficacy of different
tumor species in the dose escalation stage. Each dose level was extended to at least 10
subjects, with each patient receiving one course of treatment (21 days).
Based on the preliminary clinical trial data, the number of injections and the interval
time of administration can be adjusted during the dose expansion phase after the decision
of the Safety Monitor Committee (SMC).
Duration of treatment:
In two phases, D22 began to enter a continuous treatment period. 3 weeks (21 days) was a
course of treatment, and intravenous administration was performed on D1, 3, and 5 of each
course. Safety-related tests are required for each course of treatment. Tumor efficacy
was evaluated every 2 courses (every 6 weeks) according to RECIST1.1 and iRECIST
criteria, and pharmacodynamic tests (including tumor markers, T cell subsets, cytokines,
and viral load in tumor tissue, etc.) were performed regularly.
During the continuous treatment period, when the subject meets the criteria of 9.1
subject end of treatment, the continuous treatment period will end and the subject will
enter the long-term safety and survival follow-up period.
Long-term safety and survival follow-up:
Adverse events occurring throughout the study from the first dosing of each subject will
be collected, and long-term safety and survival follow-up will continue up to 2 years
after the last dosing (visits every 8 weeks until death or loss of follow-up, or the end
date of survival follow-up). Prior to the initiation of a new antitumor therapy, the
subjects were examined according to "6.8 Clinical Trial Schedule". After the subject has
started a new anti-tumor therapy, a telephone visit can be made to confirm the subject's
survival only.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Be fully aware of this study and voluntarily sign ICF. 2. Age range from 18 to 70
years old at the time of screening, gender is not limited.
3. At the time of screening, patients with advanced malignant digestive system tumors
confirmed by histology or cytology, including MSS type colorectal cancer, bile duct
cancer, stomach cancer, esophageal cancer, liver cancer, etc.
4. At the time of screening, the disease has progressed after or during standard
treatment; Subjects with advanced malignant digestive system tumors with no standard
treatment currently available, intolerance to chemotherapy, or greater than or equal
to progression after 2-line system therapy.
1. Be fully aware of this study and voluntarily sign ICF.
2. Age range from 18 to 70 years old at the time of screening, gender is not limited.
3. At the time of screening, patients with advanced malignant digestive system tumors
confirmed by histology or cytology, including MSS type colorectal cancer, bile duct
cancer, stomach cancer, esophageal cancer, liver cancer, etc.
4. At the time of screening, the disease has progressed after or during standard
treatment; Subjects with advanced malignant digestive system tumors with no standard
treatment currently available, intolerance to chemotherapy, or greater than or equal
to progression after 2-line system therapy.
5. When screening, the ECOG score of physical strength score is 0 or 1.
6. Life expectancy assessed by the investigator at the time of screening was ≥3 months.
7. Subjects had adequate organ function at baseline:
a) Bone marrow function (no growth factor support therapy or component transfusion
within 14 days prior to screening) : i. Neutrophil absolute value (ANC) ≥1.5×109/L;
ii. Hemoglobin (HB) ≥90g/L; iii. Platelet count (PLT) ≥75×109/L; b) Liver function:
i. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 times
the upper limit of normal (ULN) (ALT and AST≤ 3 times ULN for liver metastasis or
hepatocellular carcinoma); ii. Total blood bilirubin ≤ 1.5 ULN (in subjects with
liver metastasis or hepatocellular carcinoma or Gilbert syndrome or familial benign
nonbinding hyperbilirubinemia, the acceptable range of this indicator is ≤2.5 ULN);
c) Renal function: serum creatinine ≤ 1.5x ULN or creatinine clearance ≥50mL/min;
8. Fertile female subjects must have negative blood beta-HCG test results within 7 days
prior to enrollment.
9. Subjects must agree to use highly effective contraception for at least 90 days from
the start of the ICF to the end of the study.
Exclusion Criteria:
1. At the time of screening, advanced malignant tumors have a chance of being cured by
radical treatment.
2. Asymptomatic brain metastases such as untreated ones at the time of screening;
Subjects with symptomatic central nervous system (CNS) metastatic or cancerous
meningitis; Or there was other evidence of uncontrolled central nervous system or
meningeal metastases in subjects who were judged by the investigator to be
unsuitable for enrollment.
3. Prior to enrollment, there was severe chronic or active infection: active hepatitis
B (HbsAg positive, HBV DNA test value greater than the upper limit of normal);
Active hepatitis C (those with positive anti-HCV antibodies are further tested
positive for HCV RNA); A known history of immunodeficiency virus (HIV) disease or a
positive HIV antibody test; Other conditions requiring systemic anti-infective
treatment in the 4 weeks prior to initial use of the investigational drug include,
but are not limited to, hospitalization for infectious complications, bacteremia,
severe pneumonia, or active tuberculosis.
4. At the time of screening, patients had a history of active autoimmune diseases such
as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc., or were
receiving long-term systemic steroids (prednisone >10mg/ day or equivalent doses of
the same drug) or any other form of immunosuppressant therapy within 14 days prior
to the first use of the study drug.
5. Have received allogeneic tissue or solid organ transplantation.
6. There is evidence of clinically significant immunodeficiency, such as primary
immunodeficiency status, such as severe combined immunodeficiency disease (SCID);
Combined with opportunistic infections.
7. Anticoagulants or antiplatelet drugs should be used before injection and should not
be interrupted, including: aspirin should not be stopped within 7 days before
injection; Coumarin that cannot be stopped within 7 days prior to injection; Direct
thrombin inhibitors (such as dabigatrun) or direct factor Xa inhibitors (such as
rivaroxaban, apixaban, and neperoxaban) that cannot be discontinued within 4 days
prior to injection; Low molecular weight heparin (LMWH) should not be stopped within
24 hours before injection, and ordinary heparin (UFH) should not be stopped more
than 4 hours before injection.
8. Have a history of severe cardiovascular and cerebrovascular disease, including but
not limited to: congestive heart failure ≥II heart function grade of the New York
Heart Association (NYHA); Left ventricular ejection fraction (LVEF) <50%; QT
interval (QTcF) >470ms as corrected by the Fridericia method or prolonged QT
interval syndrome; Acute coronary syndrome, aortic dissection, severe arrhythmia,
stroke, or other grade 3 or higher cardiovascular and cerebrovascular events
occurred within 6 months before first administration; The presence of uncontrolled
hypertension (systolic blood pressure >140mmHg or diastolic blood pressure >90mmHg).
Subjects with a history of hypertension are admitted to the study if their blood
pressure is controlled below this standard and maintained with antihypertensive
therapy.
9. Received treatment with other methods, including but not limited to chemotherapy,
radiotherapy, biotherapy, endocrine therapy, immunotherapy, etc., within 4 weeks
prior to the first use of the investigational drug.
10. Other diseases or abnormalities assessed by the investigator as unsuitable for
participation in the study.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Beijing Cancer Hospital
Address:
City:
Beijing
Country:
China
Status:
Recruiting
Contact:
Last name:
Lin Shen
Phone:
+86 10 8819 6561
Email:
doctorshenlin@sina.cn
Start date:
May 6, 2024
Completion date:
October 30, 2027
Lead sponsor:
Agency:
Peking University
Agency class:
Other
Source:
Peking University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06380309
