Phase I Clinical Study of GB222 to Evaluate the Safety, Tolerability and PK Profiles.

NCT04178057 | Unknown Phase 1

• 1 other identifier: GENOR GB222-003; V2.1
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to assess the safety and tolerability, pharmacokinetic profiles, immunogenicity of GB222 in Chinese patients with relapsed/progressive high-grade glioma; moreover, changes in cerebral edema, changes in KPS score from baseline, objective response rate (ORR), 4-month progression-free survival (PFS), overall survival (OS)will be evaluated. The dose reduction of hormone during continuous administration period will be observed.

Conditions

Brain Tumor

Outcome Measures

Primary Outcomes (4)

• Dose-limiting toxicity, DLT

  Dose-limiting toxicity, DLT

  up to 28 days

• Maximum Tolerated Dose, MTD

  Maximum Tolerated Dose, MTD

  up to 28 days

• Serious Adverse Effect, SAE

  Serious Adverse Effect, SAE

  up to 28 days

• Adervse Effect, AE

  Adervse Effect, AE

  up to 28 days

Secondary Outcomes (10)

• Cmax

  up to 28 days

• AUC 0-t

  up to 28 days

• AUC (0- ∞)

  up to 28 days

• Tmax

  up to 28 days

• T 1/2

  up to 28 days

Study Arms (4)

GB222 3mg/kg

EXPERIMENTAL

GB222 3mg/kg

Biological: GB222 3mg/kg

GB222 5mg/kg

EXPERIMENTAL

GB222 5mg/kg

Biological: GB222 5mg/kg

GB222 7.5mg/kg

EXPERIMENTAL

GB222 7.5mg/kg

Biological: GB222 7.5mg/kg

GB222 10mg/kg

EXPERIMENTAL

GB222 10mg/kg

Biological: GB222 10mg/kg

Interventions

GB222 3mg/kg BIOLOGICAL

Injection, strength 100mg/bottle, intravenous infusion, 3mg/kg, dose escalation; After it is tolerated, 2 weeks/per time, combines use of chemotherapeutic agents is allowed after 3 months until disease progression, death, intolerable toxic reactions, withdrawal of informed consent form, loss to follow-up, death or study conclusion; low dose group.

Also known as: Recombinant humanized antivascular endothelial growth factor monoclonal antibody injection

GB222 3mg/kg

GB222 5mg/kg BIOLOGICAL

Injection, strength 100mg/bottle, intravenous infusion,5mg/kg, dose escalation; After it is tolerated, 2 weeks/per time, combines use of chemotherapeutic agents is allowed after 3 months until disease progression, death, intolerable toxic reactions, withdrawal of informed consent form, loss to follow-up, death or study conclusion; intermediate dose group 1.

Also known as: Recombinant humanized antivascular endothelial growth factor monoclonal antibody injection

GB222 5mg/kg

GB222 7.5mg/kg BIOLOGICAL

Injection, strength 100mg/bottle, intravenous infusion,7.5mg/kg, dose escalation; After it is tolerated, 2 weeks/per time, combines use of chemotherapeutic agents is allowed after 3 months until disease progression, death, intolerable toxic reactions, withdrawal of informed consent form, loss to follow-up, death or study conclusion; intermediate dose group 2.

Also known as: Recombinant humanized antivascular endothelial growth factor monoclonal antibody injection

GB222 7.5mg/kg

GB222 10mg/kg BIOLOGICAL

Injection, strength 100mg/bottle, intravenous infusion,10mg/kg, dose escalation; After it is tolerated, 2 weeks/per time, combines use of chemotherapeutic agents is allowed after 3 months until disease progression, death, intolerable toxic reactions, withdrawal of informed consent form, loss to follow-up, death or study conclusion; high dose group.

Also known as: Recombinant humanized antivascular endothelial growth factor monoclonal antibody injection

GB222 10mg/kg

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years, male or female;
• Understand the study procedures and contents, and voluntarily sign the written informed consent form;
• Histologically or cytologically confirmed advanced high-grade glioma which failed respond to conventional treatment and is unsuitable to receive multidisciplinary treatment, WHO grades III-IV;
• Disease progression (recurrence) after first-line treatment including surgery, radiotherapy and temozolomide chemotherapy;
• MRI confirmed tumor progression (within 14 days before the administration of investigational product);
• KPS score ≥50;
• Life expectancy≥3 months;
• The resection of relapsed brain tumors is performed at least 4 weeks before the use of investigational products, or sereotactic mamography biopsy of brain tumors is performed at least 2 weeks before the use of investigational products;
• The radiotherapy is performed at least 12 weeks before the use of investigational products, unless that the size increased of relapsed tumor is larger than that of the site received radiotherapy or histologically confirmed tumor progression;
• The chemotherapy is completed at least 4 weeks before the use of investigational products;
• At least one measurable and evaluable tumor lesion (in accordance with RANO criteria);
• The investigational products can be used after 5 half-lives of other previously used investigational products, after 4 weeks of cytotoxic agents (23 days for temozolomide, 6 weeks for nitrosoureas) and after 4 weeks of monoclonal antibodies (or 5 half-lives, whichever is longer);
• Subjects who have no serious hematological, cardiopulmonary, hepatorenal disease, hemoglobin (Hb) ≥9g/dl, white blood cell count ≥3.5×109/L, neutrophil ≥1.5×109/L, platelet≥100×109/L; serum creatinine (Cr) ≤1.5xULN or calculated value of creatinine clearance \*≥50mL/min; urine protein \< 2+ or less than 1.0g/L (if urine protein in routine urine test is ≥2+ or 1.0g/L at baseline, quantitative test of 24h urinary protein shall be performed. If it is \< 1g/24 hours, the subjects can be enrolled); total bilirubin \< 1.0xULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<2.5xULN; international normalized ratio (INR) ≤1.0xULN, and prothrombin time (PT) and activated partial thromboplastin time (APTT)≤1.0xULN;
• Females of child-bearing potential have negative pregnancy test; males or females agree to adopt medically confirmed effective contraceptive measures during the entire study period and within 6 months after the end of this study.
• Patients can receive follow-up visits as scheduled, well communicate with the investigators and complete the study as required by the study. \*Ccr for males=(140-age) × body weight (kg)/(72×Scr (mg/dl)); or Ccr for females=\[(140-age)×body weight (kg)\]/\[85×Scr (mg/dl)\]

You may not qualify if:

• The subjects are not allowed to participate in this clinical study if they meet any of the following criteria:
• Subjects with brain neoplasms which occur in brain stem;
• Subjects with diffuse meningeal dissemination;
• Subjects who previously had other malignancies (excluding cured cervical carcinoma in situ and skin basal cell carcinoma) are not allowed to participate in the study unless he/she completely relieved at least 2 years before being enrolled in this study and requires no other treatment now or during the study period.
• Subjects who have active, known or suspected autoimmune diseases;
• Subjects who received treatment with systemic immunosuppressive therapies within 6 months before the use of investigational products;
• Subjects who received large dose of systemic glucocorticoids within 2 weeks before the use of investigational products, which is equivalent to dexamethasone \>4.1mg/d or equivalent dose, administration for 3 continuous days\[3\].
• Subjects who previously received isotopic radiotherapy, implanted chemotherapy, stereotactic radiotherapy or local injection or convection-enhanced delivery (CED);
• The medical history or test results showing thrombotic diseases within 6 months before enrollment;
• Subjects who received larger surgical procedures, experienced significant trauma, or expected to receive major surgery during the study treatment period within 4 weeks before the use of investigational products;
• Subjects who received minor surgical procedures (including cannulation) within 48 hours before the use of the first monoclonal antibody and are considered to have bleeding tendency at the discretion of the investigator;
• Subjects who currently or recently (within 10 days before the first dose of monoclonal antibody) used aspirin (\>325mg/day) or other non-steroidal anti-inflammatory drugs (NSAIDs) which are known to inhibit platelet function;
• Subjects who currently or recently (within 10 days before the first dose of monoclonal antibody) are treated with whole dose of oral or parenteral anticoagulants or thrombolytic therapies;
• The medical history or test results showing hereditary bleeding tendency or coagulation disorders, thus increasing the risks of bleeding;
• Patients with complicated serious internal diseases, including uncontrolled diabetes mellitus, active gastrointestinal ulcer, active bleeding etc.;

Sponsors & Collaborators

• Genor Biopharma Co., Ltd.: lead

Study Sites (1)

Beijing Tiantan Hospital of Capital Medical University

Beijing, Beijing Municipality, 100050, China

RECRUITING

MeSH Terms

Conditions

Brain Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Wenbin Li, Ph.D

  Beijing Tiantan Hospital of Capital Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shawn Yu, Master

CONTACT

010-65260820; Shawn.Yu@genorbio.com

Study Design

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

Study Record Dates

• First Submitted: November 24, 2019
• First Posted: November 26, 2019
• Study Start: October 16, 2018
• Primary Completion: December 1, 2020
• Study Completion: April 1, 2021
• Last Updated: November 27, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)