Trial Title:
Safety and Tolerability Study of Recombinant L-IFN Adenovirus Injection in Patients With Recurrent Glioblastoma
NCT ID:
NCT05914935
Condition:
Recurring Glioblastoma
Conditions: Official terms:
Glioblastoma
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Recombinant L-IFN adenovirus injection
Description:
The Ommaya reservoir was surgically implanted, and multiple intracapsular injections were
given medicine. On the second day after Ommaya reservoir implantation, CT examination
confirmed that the implantation was successful, and the experimental drug injection was
started.
Arm group label:
Recombinant L-IFN adenovirus injection and Ommaya reservoir
Other name:
YSCH-01
Other name:
Oncolytic adenovirus
Summary:
The target subjects were patients with histologically or cytologically confirmed
recurrent glioblastoma.Six subjects were expected to be enrolled,the number of subjects
will be adjusted according to the course and outcome of the trial.The aim of this study
was to evaluate the safety and tolerability of recombinant L-IFN adenovirus injection in
the treatment of patients with recurrent glioblastoma, and to determine the registered
clinical recommended dose and dosing regimen.
Detailed description:
The IIT clinical study of recombinant L-IFN adenovirus injection is planned to adopt an
open-label, non-randomized, dose exploratory study design. The trial was divided into
screening, treatment and maintenance periods.The Ommaya reservoir was surgically
implanted, and multiple intracapsular injections were administered.The overall survival
(OS), progression-free survival (PFS) and disease control rate (DCR) were used to
evaluate the efficacy of recombinant adenovirus L-IFN injection in the treatment of
recurrent glioblastoma.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1.Voluntarily sign the informed consent and follow the requirements of the protocol; 2.18
years old ≤ age ≤75 years old, male or female; 3. Expected survival time ≥12 weeks; 4.KPS
score ≥50 before treatment; 5. Patients with pathologically and/or cytologically
confirmed glioblastoma; After conventional radiation and/or systemic therapy, the disease
recurred. PETCT/MRI of the head within 14 days before screening confirmed at least one
enhancement lesion ≥1 cm in length.
6. The patient has recovered from the toxic effects of the last treatment before the
first dose (CTCAE≤1, except for special conditions such as "alopecia" and
"pigmentation"), and the corresponding AE is judged by the investigator to be not a
safety risk; 7. Organ and bone marrow function levels must meet the following
requirements:
1. Bone marrow: Absolute neutrophil count (ANC) ≥1.5×10^9/L, platelet count
≥100×10^9/L, hemoglobin ≥90 g/L, and no platelet or red blood cell transfusion
within 14 days before the first dose; No blood transfusion or biological response
regulators (such as granulocyte stimulating growth factor, erythrocyte growth
factor, interleukin-11, etc.) within 14 days before the first dose;
2. Liver function: No history of cirrhosis (Child-Pugh class B, C decompensated
cirrhosis) Patients without liver metastasis were required to have serum total
bilirubin (TBIL) ≤1.5× upper limit of normal (ULN), alanine aminotransferase (ALT)
and aspartate aminotransferase (AST) ≤2.5×ULN. Patients with liver metastasis
required TBIL ≤1.5×ULN, ALT and AST≤5×ULN;
3. Renal function: serum creatinine ≤1.5×ULN or creatinine clearance ≥50 ml/ minute
(Cockcorft-Gault formula) Qualitative urine protein ≤1+; If urinary protein
qualitative ≥2+，24-hour urinary protein quantitative test is required. The
investigators determined the enrollment according to the examination results.
4. Coagulation: prothrombin time (PT) ≤1.5 times ULN An international normalized ratio
(INR) of 1.5×ULN or less and an activated partial thromboplastin time (APTT) of
1.5×ULN or less (except for those receiving therapeutic anticoagulants); 8. Female
participants of childbearing age must have taken a serum pregnancy test with a
negative result within 3 days before starting study medication and be willing to use
a medically approved, highly effective contraceptive (e.g., IUD, contraceptive pill,
or condom) during the study and for 5 months after last administration of study
medication; For male subjects whose partner was a woman of childbearing age, consent
was given to use an effective method of contraception for the duration of the study
and for 5 months after the last study dose.
Exclusion Criteria:
1. Previous or current history of other types of malignant tumors, except for the
following:
1. radical cutaneous basal cell carcinoma, superficial bladder cancer, cutaneous
squamous cell carcinoma, or cervical cancer in situ;
2. second primary cancer that has been cured with no recurrence within 5 years;
2. Known allergy to the study drug or any of its excipients, or a history of
unexplained severe allergic reaction;
3. Any contraindications to gadolinium contrast-enhanced MRI, such as personal use of a
pacemaker, infusion pump, or allergy to MRI contrast media;
4. Any contraindications to implantation of Ommaya reservoir;
5. Received any of the following treatments or medications before the first study
treatment:
1. major surgery or major trauma within 4 weeks before the first study drug.
(Major surgery is defined as any invasive procedure that involves extensive
resection or that requires opening of mesothelial cell barriers (e.g., pleural
space, peritoneum, meninges). However, biopsies needed for diagnosis were
permitted. Severe trauma is a wound, ulcer or fracture that does not heal;
2. administration of live attenuated vaccine within 4 weeks before or planned for
the duration of the first study drug;
3. medium (adult) drug treatment with anti-tumor indications within 2 weeks before
the first study drug treatment;
4. antineoplastic therapy (including chemotherapy, radiotherapy, immunotherapy,
targeted therapy, biological therapy or tumor embolization) within 4 weeks
before the first dose; For oral fluorouracil and endocrine therapy, drug
withdrawal ≤2 weeks; In the case of nitrosourea, mitomycin or monoclonal
antibody, drug withdrawal ≤6 weeks. If washout time is insufficient due to
schedule or PK characteristics of the drug, it needs to be discussed with the
partner;
6. Patients with symptoms, disseminated to viscera, and risk of life-threatening
complications in a short period of time, patients with pleural effusion, peritoneal
effusion, and pericardial effusion who underwent puncture and drainage within three
weeks before the first administration;
7. Subjects with active or preexisting autoimmune diseases (e.g., systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid
disease, multiple sclerosis, vasculitis, glomerulonephritis, etc.) or those at high
risk (e.g., organ transplant recipients requiring immunosuppressive therapy).
However, subjects with the following conditions were allowed:
1. patients with type I diabetes who are stable on fixed doses of insulin;
2. autoimmune hypothyroidism with hormone replacement therapy only;
3. skin conditions requiring no systemic treatment (e.g. eczema, rashes covering
less than 10% of the body surface, psoriasis without eye symptoms, etc.);
4. patients who have resolved childhood asthma/allergy without intervention in
adulthood;
8. Cardiovascular disease within 6 months before screening meets any of the following
criteria:
1. congestive heart failure with New York Heart Association (NYHA) class Ⅱ or
above; Left ventricular ejection fraction (LVEF) < 50%;
2. severe arrhythmias requiring medical treatment;
3. QTcF (Fridericia's formula) > 450 msec in a man or > 470 msec in a woman, or
the presence of risk factors for torsdes pointes, such as hypokalemia, a family
history of long QT syndrome, or a family history of arrhythmias (e.g., the
Wolff-White syndrome), as judged by the investigator to be clinically
significant;
4. a history of myocardial infarction or severe/unstable angina within 6 months
before treatment;
5. a history of thromboembolic events of grade ≥3 within the past 2 years or
receiving thrombolytic or anticoagulant therapy due to a high risk of
thrombosis;
9. Patients with sudden lung disease, interstitial lung disease or pneumonia, pulmonary
fibrosis, acute lung disease, etc. which could not be controlled after treatment,
except for local interstitial pneumonia induced by radiotherapy;
10. Uncontrolled systemic diseases, such as diabetes (fasting blood glucose ≥13.3mM),
hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100
mmHg), etc.;
11. Have a history of human immunodeficiency virus infection or other acquired or
congenital immunodeficiency diseases, or have a history of organ transplantation or
stem cell transplantation; Except for those who do not require immunosuppressive
therapy, such as corneal transplantation;
12. Evidence of active infection:
1. Hepatitis B (HBsAg positive, HBV-DNA≥500IU/ml and abnormal liver function);
2. Hepatitis C (HCV-Ab positive, HCV-RNA higher than the detection limit of
analytical method and abnormal liver function);
3. Systemic use of anti-infective agents for ≥7 days within 4 weeks before the
first dose or unexplained fever > 38.5°C during screening/before the first dose
(according to the investigator's judgment, fever caused by cancer could be
enrolled);
4. Patients with active pulmonary tuberculosis infection detected by medical
history or CT examination, or with a history of active pulmonary tuberculosis
infection within 1 year before enrollment, or with a history of active
pulmonary tuberculosis infection more than 1 year before enrollment but without
regular treatment;
13. A definite history of a previous neurological or mental disorder or a known history
of psychotropic substance abuse, alcohol abuse or drug use;
14. Received any investigational drug within 4 weeks before the first dose or was
enrolled in another clinical study (except if the patient was enrolled in an
observational, noninterventional clinical study or was in the follow-up period of an
interventional clinical study; or more than 5 half-lives of the last study
medication);
15. Women who are pregnant or lactating, or who have a positive baseline pregnancy test;
16. Patients deemed by the investigator to be ineligible for inclusion in the study.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Binhai Hospital of Fujian Medical University
Address:
City:
Fujian
Zip:
350005
Country:
China
Status:
Recruiting
Contact:
Last name:
Dezhi Kang, PhD
Phone:
13859099988
Email:
kirby98@126.com
Start date:
June 27, 2023
Completion date:
December 30, 2024
Lead sponsor:
Agency:
Binhai Hospital of Fujian Medical University
Agency class:
Other
Collaborator:
Agency:
Shanghai Yuansong Biotechnology Co., LTD
Agency class:
Other
Source:
Binhai Hospital of Fujian Medical University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05914935
