Safety and Tolerability Study of Recombinant L-IFN Adenovirus Injection in Patients With Recurrent Glioblastoma

NCT05914935 | Unknown Early Phase 1

• 1 other identifier: YSCH-01-001
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Recurring Glioblastoma

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicities (DLT)

  To define the maximum tolerated dose (MTD) of intratumoral administration of Recombinant L-IFN adenovirus injection in humans with malignant tumors

  Up to 28 days

• Safety and tolerability assessed by Adverse Events (AEs)

  An AE is any untoward medical occurrence in a subject administered an investigational product (IP), and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IP whether or not considered related to the IP

  Up to 6 months

Secondary Outcomes (3)

• Overall survival (OS)

  3.5 years

• Presence of neutralizing antibodies of antidrug antibodies (ADAs) development

  Up to 6 months

• Quality of life (QOL)

  18 months

Study Arms (1)

Recombinant L-IFN adenovirus injection and Ommaya reservoir

EXPERIMENTAL

Recombinant L-IFN adenovirus injection was locally injected through the Ommaya reservoir.A single injection dose of 5.0×10\^10 VP (total dose per injection) was administered during the treatment period.

Drug: Recombinant L-IFN adenovirus injection

Interventions

Recombinant L-IFN adenovirus injection DRUG

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.

Also known as: YSCH-01, Oncolytic adenovirus

Recombinant L-IFN adenovirus injection and Ommaya reservoir

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• \. 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:
• 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;
• 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;
• 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.
• 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.

You may not qualify if:

• Previous or current history of other types of malignant tumors, except for the following:
• radical cutaneous basal cell carcinoma, superficial bladder cancer, cutaneous squamous cell carcinoma, or cervical cancer in situ;
• second primary cancer that has been cured with no recurrence within 5 years;
• Known allergy to the study drug or any of its excipients, or a history of unexplained severe allergic reaction;
• Any contraindications to gadolinium contrast-enhanced MRI, such as personal use of a pacemaker, infusion pump, or allergy to MRI contrast media;
• Any contraindications to implantation of Ommaya reservoir;
• Received any of the following treatments or medications before the first study treatment:
• 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;
• administration of live attenuated vaccine within 4 weeks before or planned for the duration of the first study drug;
• medium (adult) drug treatment with anti-tumor indications within 2 weeks before the first study drug treatment;
• 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;
• 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;
• 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:
• patients with type I diabetes who are stable on fixed doses of insulin;
• autoimmune hypothyroidism with hormone replacement therapy only;

Sponsors & Collaborators

• Binhai Hospital of Fujian Medical University: lead
• Shanghai Yuansong Biotechnology Co., LTD: collaborator

Study Sites (1)

Binhai Hospital of Fujian Medical University

Fujian, Fujian, 350005, China

RECRUITING

Study Officials

• Dezhi Kang, PhD

  First Affiliated Hospital of Fujian Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dezhi Kang, PhD

CONTACT

13960920021; kirby98@126.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2023
• First Posted: June 22, 2023
• Study Start: June 27, 2023
• Primary Completion: June 12, 2024
• Study Completion: December 30, 2024
• Last Updated: June 28, 2023

Record last verified: 2023-06

Locations

CN (1)