A Phase I Clinical Study of Intratumoral Injection GC001 in Patient With Recurrent or Progressive Gliomas

NCT06660056 | Recruiting Phase 1

• 1 other identifier: GONGCHU Bio
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief 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 .

Conditions

High-grade Gliomas

Keywords

Oncolytic virus; GC001; WR; high-grade gliomas

Outcome Measures

Primary Outcomes (2)

• Evaluate the safety and tolerability of GC001

  Number of participants in dose escalating cohorts with dose limiting toxicities (DLTs)，treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.

  DLT Observation Period，Up to 28 days from GC001 injection

• Maximal tolerable dose

  During the DLT observation period, the number of cases with DLT is less than or equal to the maximum dose of 1/6 of the total number of cases, and six evaluable participants are required to determine MTD.

  DLT Observation Period,Up to 28 days from GC001 injection

Secondary Outcomes (2)

• Anti-tumor activity of GC001: response assessment of neuro-oncology(RANO).

  Up to 2 years

• Anti-tumor activity of GC001: immunotherapy response assessment for neuro-oncology (iRANO).

  Up to 2 years from GC001 injection

Other Outcomes (5)

• Evaluate the viral biological distribution and shedding of GC001

  Up to 2 years from GC001 injection

• Pharmacodynamic analysis of cytokine levels in the peripheral blood and omaya cyst aqueous.

  Up to 2 years from GC001 injection

• Pharmacodynamic analysis of PD-1 and lymphocyte in the peripheral blood and omaya cyst aqueous

  Up to 2 years from GC001 injection

Study Arms (2)

Part 1: Dose Escalation

EXPERIMENTAL

The study consists of a total of seven dose groups, with the lowest dose group being 1×10\^6 and the highest dose reaching 1×10\^9 PFU.To avoid exposing too many subjects to an ineffective dose, accelerated titration will be used for the 1 x 10\^6 pfu and 3 x 10\^6 pfu dose groups. The 1×10\^7-1×10\^9 pfu dose group will be dose-escalated using the traditional "3+3" design. In case the maximum dose of 1×10\^9 PFU fails to achieve the Maximum Tolerated Dose (MTD), the sponsor and the investigator will convene to discuss whether to designate it as Maximum Feasible Dose (MFD) or consider escalating further based on current safety and preliminary efficacy data. However, any escalation beyond that of similar drugs' Phase I clinical trials, such as JX-594:NCT00629759 and JX-929:NCT00574977, where the highest administered dose was 3×10\^9 PFU, shall be avoided. This precaution ensures adherence to established safety protocols.

Biological: A Phase I Clinical Study of Intratumoral Injection Oncolytic Vaccinia Virus GC001 in Patient With Recurrent or Progressive Gliomas of the Brain

Part 2:metrological amplification stage

EXPERIMENTAL

Based on the MTD determined during the dose-escalation phase (or the investigator's or sponsor's assessment to select a more appropriate dose), patients with recurrent or progressive gliomas who standard therapy failure or intolerance will be included, and will be enrolled 10 to 30 subjects.

Biological: A Phase I Clinical Study of Intratumoral Injection Oncolytic Vaccinia Virus GC001 in Patient With Recurrent or Progressive Gliomas of the Brain

Interventions

A Phase I Clinical Study of Intratumoral Injection Oncolytic Vaccinia Virus GC001 in Patient With Recurrent or Progressive Gliomas of the Brain BIOLOGICAL

Use of Ommaya capsules

Part 1: Dose Escalation; Part 2:metrological amplification stage

Eligibility Criteria

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

You may qualify if:

• To be eligible for participation in this study, individuals must meet the following criteria:
• Subjects must be able to comprehend and voluntarily sign written informed consent, which includes requirements related to study sample collection.
• 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.
• Be male or female patients aged 18 (including those with borderline age values).
• 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).
• At least 1 intracranial measurable lesion according to RANO criteria (well-defined enhancing lesion detected on MRI, diameter \>10 mm).
• Patient's willingness to undergo surgical maneuvers related to placement of the Ommaya capsule.
• Karnofsky functional status ≥ 60.
• Be expected to survive for at least 3 months.
• 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.

You may not qualify if:

• Inability to perform an MRI for any reason.
• focal point under the curtain.
• Prior history of encephalitis, multiple sclerosis, or other central nervous system infection (unless resolved).
• 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.
• Females of childbearing age who have a positive pregnancy test or are lactating.
• Individuals with allergies (defined as ≥2 drug allergies) or hypersensitivity to similar products or excipients.
• Those who have received smallpox vaccination and experienced severe systemic reactions or side effects.
• Patients who have previously received lysosomal virus, stem cell, or gene therapy products.
• 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).
• 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 who have undergone surgery or interventional therapy (excluding tumor biopsy, puncture, Ommaya capsule etc.).
• 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:
• short-term (≤7 days) use of corticosteroids for prophylaxis or treatment of non-autoimmune allergic diseases is permitted;
• the use of topical topical or inhaled glucocorticoids is permitted;.
• A history of severe cardiovascular disease, including but not limited to:

Sponsors & Collaborators

• GONGCHU Biotechnology Co., Ltd: lead

Study Sites (1)

Beijing Tiantan Hospital,Capital Medical University

Beijing, Beijing Municipality, 100000, China

RECRUITING

Study Officials

• li gongchu, Professor

  GONGCHU Biotechnology Co., Ltd

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mo guoyu

CONTACT

13710803863; morlon_pla@126.com

li wenbin, Professor

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 3+3

Study Record Dates

• First Submitted: October 24, 2024
• First Posted: October 26, 2024
• Study Start: October 8, 2024
• Primary Completion: February 8, 2026
• Study Completion (Estimated): August 8, 2026
• Last Updated: March 13, 2025

Record last verified: 2024-10

Locations

CN (1)