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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04178057
Recruitment Status : Recruiting
First Posted : November 26, 2019
Last Update Posted : November 27, 2019
Sponsor:
Information provided by (Responsible Party):
Genor Biopharma Co., Ltd.

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.

Condition or disease Intervention/treatment Phase
Brain Tumor Biological: GB222 3mg/kg Biological: GB222 5mg/kg Biological: GB222 7.5mg/kg Biological: GB222 10mg/kg Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Dose-escalated, Phase I Clinical Trial to Assess the Safety, Tolerability and Pharmacokinetic Profiles of GB222 in Chinese Patients With Relapsed/Progressive High-grade Glioma
Actual Study Start Date : October 16, 2018
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : April 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: GB222 3mg/kg
GB222 3mg/kg
Biological: GB222 3mg/kg
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.
Other Name: Recombinant humanized antivascular endothelial growth factor monoclonal antibody injection

Experimental: GB222 5mg/kg
GB222 5mg/kg
Biological: GB222 5mg/kg
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.
Other Name: Recombinant humanized antivascular endothelial growth factor monoclonal antibody injection

Experimental: GB222 7.5mg/kg
GB222 7.5mg/kg
Biological: GB222 7.5mg/kg
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.
Other Name: Recombinant humanized antivascular endothelial growth factor monoclonal antibody injection

Experimental: GB222 10mg/kg
GB222 10mg/kg
Biological: GB222 10mg/kg
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.
Other Name: Recombinant humanized antivascular endothelial growth factor monoclonal antibody injection




Primary Outcome Measures :
  1. Dose-limiting toxicity, DLT [ Time Frame: up to 28 days ]
    Dose-limiting toxicity, DLT

  2. Maximum Tolerated Dose, MTD [ Time Frame: up to 28 days ]
    Maximum Tolerated Dose, MTD

  3. Serious Adverse Effect, SAE [ Time Frame: up to 28 days ]
    Serious Adverse Effect, SAE

  4. Adervse Effect, AE [ Time Frame: up to 28 days ]
    Adervse Effect, AE


Secondary Outcome Measures :
  1. Cmax [ Time Frame: up to 28 days ]
    Cmax

  2. AUC 0-t [ Time Frame: up to 28 days ]
    AUC 0-t

  3. AUC (0- ∞) [ Time Frame: up to 28 days ]
    AUC (0- ∞)

  4. Tmax [ Time Frame: up to 28 days ]
    Tmax

  5. T 1/2 [ Time Frame: up to 28 days ]
    T 1/2

  6. CL [ Time Frame: up to 28 days ]
    CL

  7. Antidrug Antibody, ADA [ Time Frame: through study completion, an average of 2 year ]
    Antidrug Antibody, ADA

  8. Objective Response Rate, ORR [ Time Frame: through study completion, an average of 2 year ]
    Objective Response Rate, ORR

  9. Progress-free Survial, PFS [ Time Frame: through study completion, an average of 2 year ]
    Progress-free Survial, PFS

  10. Overall Survial, OS [ Time Frame: through study completion, an average of 2 year ]
    Overall Survial, OS



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

The patients can be enrolled only if they meet the following all inclusion criteria:

  1. Age ≥ 18 years, male or female;
  2. Understand the study procedures and contents, and voluntarily sign the written informed consent form;
  3. 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;
  4. Disease progression (recurrence) after first-line treatment including surgery, radiotherapy and temozolomide chemotherapy;
  5. MRI confirmed tumor progression (within 14 days before the administration of investigational product);
  6. KPS score ≥50;
  7. Life expectancy≥3 months;
  8. 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;
  9. 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;
  10. The chemotherapy is completed at least 4 weeks before the use of investigational products;
  11. At least one measurable and evaluable tumor lesion (in accordance with RANO criteria);
  12. Prior to the use of investigational product, all adverse reactions related to the previous treatment must recover to the level specified in the inclusion criteria, grade 0 or 1 (the following is excluded -including but not limited to alopecia, laboratory parameters in the inclusion criteria and common lymphocytopenia after temozolomide treatment);
  13. 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);
  14. 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;
  15. 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.
  16. 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)]

Exclusion criteria:

The subjects are not allowed to participate in this clinical study if they meet any of the following criteria:

  1. Subjects with brain neoplasms which occur in brain stem;
  2. Subjects with diffuse meningeal dissemination;
  3. 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.
  4. Subjects who have active, known or suspected autoimmune diseases;
  5. Subjects who received treatment with systemic immunosuppressive therapies within 6 months before the use of investigational products;
  6. 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].
  7. Subjects who previously received isotopic radiotherapy, implanted chemotherapy, stereotactic radiotherapy or local injection or convection-enhanced delivery (CED);
  8. The medical history or test results showing thrombotic diseases within 6 months before enrollment;
  9. 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;
  10. 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;
  11. 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;
  12. 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;
  13. The medical history or test results showing hereditary bleeding tendency or coagulation disorders, thus increasing the risks of bleeding;
  14. Patients with complicated serious internal diseases, including uncontrolled diabetes mellitus, active gastrointestinal ulcer, active bleeding etc.;
  15. Uncontrolled hypertension (systolic blood pressure >140 mmHg and/or diastolic pressure > 90 mmHg);
  16. Patients who previously have hypertensive crisis or hypertensive encephalopathy;
  17. Subjects with clinical significant (e.g., active) cerebrovascular diseases, e.g., cerebrovascular accident (CVA) or transient ischemic attack (TIA) (≤6 months before enrollment), myocardial infarction (≤6 months before enrollment), unstable angina pectoris, congestive heart failure (New York Heart Association grade III or above), subjects who require drug therapies during the study period which may interfere study treatment, or subjects with serious arrhythmia which cannot be controlled by drugs;
  18. Subjects with significant vascular diseases within 6 months before the use of investigational products (including but not limited to aortic aneurysm requiring repair surgery or recent artery thrombosis);
  19. Subjects with non-cured wound, active peptic ulcer or fracture;
  20. Subjects who are diagnosed with tracheoesophageal fistula;
  21. Subjects who have medical history of abdominal fistula, gastrointestinal perforation or intraperitoneal abscess;
  22. Subjects who have active infection (≥CTCAE grade 2);
  23. Previously or currently suffering from active pulmonary tuberculosis (TB) infection;
  24. Any of the following is positive: hepatitis C antibody (HCV-Ab), acquired immunodeficiency syndrome antibody (Anti-HIV) and anti-treponema pallidum antibody (TP-Ab);
  25. Positive hepatitis B surface antigen (HBsAg) and peripheral blood hepatitis B virus deoxyribonucleic acid (HBV-DNA) >103 copies/L, if HBV-DNA titer test <103 copies/L, and the investigator considers that chronic hepatitis B is stable and cannot increase the risks, the subjects can be enrolled;
  26. Patients who had used other investigationsl drugs within 28 days before the use of this investigational drug or within 5 half-lives of the previous investigational drugs (whichever is longer) or had used investigational medical device within 28 days;
  27. Patients who received any anti-infection vaccines (e.g. influenza vaccine, varicella vaccine etc.) within 4 weeks before enrollment;
  28. Subjects with drug addiction or alcohol addiction (i.e., weekly alcohol consumption > 14 units, one unit of alcohol=360ml of beer or 45ml 40% liquor or 150 mL of wine)
  29. Subjects with interstitial lung disease and clinical symptoms;
  30. Subjects with peripheral neuropathy ≥ CTCAE grade 2
  31. Subjects who are known to be allergic to anti-VEGF monoclonal antibody or any of its excipients, or subjects who are known to have medical history of allergic diseases or allergic constitution;
  32. Subjects who received anti-VEGF monoclonal antibody or similar products before the study;
  33. Pregnant and lactating women;
  34. Patients who have poor compliance, self-care disability and cannot guarantee to follow the protocol requirements;
  35. Subjects who are considered unsuitable for participating in this study for various reasons at the discretion of the investigator.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04178057


Contacts
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Contact: Shawn Yu, Master 010-65260820 Shawn.Yu@genorbio.com

Locations
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China, Beijing
Beijing Tiantan Hospital of Capital Medical University Recruiting
Beijing, Beijing, China, 100050
Contact: Wenbin Li, Ph.D    010-67098416    neure55@126.com   
Sponsors and Collaborators
Genor Biopharma Co., Ltd.
Investigators
Layout table for investigator information
Principal Investigator: Wenbin Li, Ph.D Beijing Tiantan Hospital of Capital Medical University

Layout table for additonal information
Responsible Party: Genor Biopharma Co., Ltd.
ClinicalTrials.gov Identifier: NCT04178057    
Other Study ID Numbers: GENOR GB222-003; V2.1
First Posted: November 26, 2019    Key Record Dates
Last Update Posted: November 27, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Brain Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Antineoplastic Agents, Immunological
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Mitogens
Endothelial Growth Factors
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Growth Substances