4006-776-356 出国就医服务电话

免费获得国外相关药品,最快 1 个工作日回馈药物信息

出境医 / 临床实验 / Phase I Study of Hemay102 in Patients With Advanced Solid Tumors

Phase I Study of Hemay102 in Patients With Advanced Solid Tumors

Study Description
Brief Summary:
This trial was a single-center, open-label, dose-increasing Phase I clinical study with subjects enrolled in patients with advanced solid tumors who failed standard treatment or who were unable to receive effective treatment. The trial is divided into two stages: dose escalation and dose extension.

Condition or disease Intervention/treatment Phase
Patients With Advanced Stage Solid Tumors Drug: Hemay102 Phase 1

Detailed Description:

Dose escalation:

A total of 7 dosage groups were set at this stage, which were 5 mg/m2, 10 mg/m2, 20 mg/m2, 40 mg/m2, 60 mg/m2, 90 mg/m2, and 120 mg/m2, respectively. Accelerated dosage titration was performed in the first 3 dose groups, 1 subject was enrolled in each group; the last 4 dose groups were perfromed into dosage groups by the principle of "3+3" dose increment rule, and the number of subjects enrolled in each group is 3 to 6 cases.

Dose extension:

According to the test results of the dose escalation phase, two extensions of MTD (tentative 60 mg/m2, 90 mg/m2) were selected for the expansion trial. Each dose level was planned to enroll 6 subjects (12 in total), subjects were administered once every 3 weeks (1 treatment cycle every 3 weeks), and received 4 treatment cycles in a row for Hemay102. Safety, tolerability, pharmacokinetic characteristics, and initial anti-tumor efficacy were evaluated.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 39 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Masking Description: open-label
Primary Purpose: Treatment
Official Title: A Dose Escalation Phase I Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Antitumor Efficacy of Hemay102 in Patients With Advanced Solid Tumors
Actual Study Start Date : January 3, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021
Arms and Interventions
Arm Intervention/treatment
Experimental: Hemay102 at the dosage of 5mg/m2
Hemay102 will be administered to patients through i.v. drip for 4hrs at the dosage of 5mg/m2.
Drug: Hemay102
Hemay102 was administered through i.v. infusion for 4hrs.

Experimental: Hemay102 at the dosage of 10mg/m2
Hemay102 will be administered to patients through i.v. drip for 4hrs at the dosage of 10mg/m2.
Drug: Hemay102
Hemay102 was administered through i.v. infusion for 4hrs.

Experimental: Hemay102 at the dosage of 20mg/m2
Hemay102 will be administered to patients through i.v. drip for 4hrs at the dosage of 20mg/m2.
Drug: Hemay102
Hemay102 was administered through i.v. infusion for 4hrs.

Experimental: Hemay102 at the dosage of 40mg/m2
Hemay102 will be administered to patients through i.v. drip for 4hrs at the dosage of 40mg/m2.
Drug: Hemay102
Hemay102 was administered through i.v. infusion for 4hrs.

Experimental: Hemay102 at the dosage of 60mg/m2
Hemay102 will be administered to patients through i.v. drip for 4hrs at the dosage of 60mg/m2.
Drug: Hemay102
Hemay102 was administered through i.v. infusion for 4hrs.

Experimental: Hemay102 at the dosage of 90mg/m2
Hemay102 will be administered to patients through i.v. drip for 4hrs at the dosage of 90mg/m2.
Drug: Hemay102
Hemay102 was administered through i.v. infusion for 4hrs.

Experimental: Hemay102 at the dosage of 120mg/m2
Hemay102 will be administered to patients through i.v. drip for 4hrs at the dosage of 120mg/m2.
Drug: Hemay102
Hemay102 was administered through i.v. infusion for 4hrs.

Outcome Measures
Primary Outcome Measures :
  1. Number of participants with adverse events [ Time Frame: from baseline until 4 weeks after the study day ]
    Number of participants with adverse events


Secondary Outcome Measures :
  1. Objective response rate [ Time Frame: At screening, every 6 weeks of treatment up to 18 months ]
    Objective response rate (complete response rate + partial response rate) according to RECIST v1.1

  2. Clinical benefit rate [ Time Frame: At screening, every 6 weeks of treatment up to 18 months ]
    Clinical benefit rate defined as percentage of patients with stable disease (SD) ≥ 6 months/partial response (PR)/complete response (CR). according to RECIST v1.1

  3. Progression Free Survival [ Time Frame: 18 months after treatment initiation ]
    Progression Free Survival defined as the proportion of patients alive and without progression (according to RECIST v1.1 criteria)

  4. AUC [ Time Frame: 0, 1, 2, 3, 5, 8, 12, 24, 48 and 72 hours post-dose ]
    Area under the plasma concentration versus time curve of Hemay102


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥18 years old and ≤70 years old, male or female;
  • A patient who has been confirmed by histology or cytology to have advanced or metastatic solid tumors (in the patients with locally advanced hepatocellular carcinoma or metastatic liver cancer, patients can be recruited by clinical diagnosis) and who have failed standard treatment or who are unable to receive/do not have effective treatment;
  • At least one evaluable tumor lesion (spiral CT scan with a long diameter ≥ 10 mm, in accordance with RECIST version 1.1);
  • ECOG PS score 0~1 within 1 week before enrollment;
  • Estimated survival time of more than 3 months;
  • Appropriate hematopoietic function: white blood cell count ≥ 3 × 10^9 / L; absolute neutrophil count ≥ 1.5 × 10^9 / L; platelet count ≥ 100 × 10^9 / L; hemoglobin ≥ 90 g / L;
  • Appropriate liver function: total bilirubin ≤ 1.5 × upper limit of normal (ULN); aspartate transferase (AST) ≤ 2.5 × ULN; alanine aminotransferase (ALT) ≤ 2.5 × ULN;
  • Proper renal function: serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL / min according to the Cockcroft-Gault formula;
  • For clinically confirmed unresectable locally advanced hepatocellular carcinoma or metastatic liver cancer, the patient's liver function must meet the criteria below: ALT≤2.5×ULN, AST≤2.5×ULN, TBIL≤1.5×ULN, Child-Pugh score A or B Grade (≤7 points), blood ammonia ≤100μmol/L (only for patients with hepatocellular carcinoma);
  • A qualified male or female patient with fertility must agree to use a reliable method of contraception (hormone or barrier method) after signing the informed consent until at least 12 weeks after the last dose;
  • Subjects must give informed consent to the study prior to the trial and voluntarily sign a written informed consent form;
  • Subjects are able to communicate well with the investigator and are able to complete the study in accordance with the trial regulations.

Exclusion Criteria:

  • Subjects known to have or suspected to have brain metastases;
  • Have received radiation therapy within 4 weeks before enrollment;
  • Drugs that may affect the metabolism of this product, such as CYP3A4 strong inducer (rifampicin, carbamazepine, phenytoin, etc.) or strong inhibitors (clarithromycin, protease, triazole antifungals, etc.), should be combined within 2 weeks before the study or during the study period;
  • Patients who have previously received anthracycline treatment; or who are known to have a history of allergies to anthracyclines (eg, doxorubicin, epirubicin);
  • Have active infection or HIV-positive infection or other serious illness;
  • Untreated active hepatitis C (anti-HCV antibody positive and HCV RNA positive patients cannot be enrolled); untreated active hepatitis B (HBsAg positive and HBV DNA ≥ 2000 IU/mL) (Note: Hepatitis B subjects treated with treatment also met the inclusion criteria if the following criteria were met: HBV viral load was less than 2000 IU/mL before the first dose of study drug, or patients who are on HBV treatment, and patients with viral load lower than 2000 IU/mL can also be enrolled);
  • Uncontrolled or important cardiovascular disease, which included a) New York Heart Association (NYHA) grade II or higher congestive heart failure, unstable angina, myocardial infarction, or arrhythmia requiring treatment (including atrial fibrillation, at screening) within 6 months prior to the first study drug administration Supraventricular tachycardia, ventricular tachycardia or ventricular fibrillation, or left ventricular ejection fraction (LVEF) < 50%; b) Primary cardiomyopathy (eg dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, undetermined cardiomyopathy); c) Clinically significant QTc interval prolongation history, or screening period QTc interval (corrected by Bazette) ≥ 450ms (male) or ≥ 470ms (female); d) Coronary heart disease with symptoms requiring medication; e) Uncontrollable hypertension (refers to post-treatment systolic blood pressure > 160 mmHg and / or diastolic blood pressure > 100 mmHg);
  • A history of hemorrhagic or thromboembolic events in the past 6 months, such as cerebrovascular accidents (including transient ischemic attacks), pulmonary embolism, and spontaneous bleeding of the tumor;
  • Medical treatment for other clinical trials within 4 weeks prior to enrollment;
  • <4 weeks after major surgery or trauma after enrollment;
  • Must take other treatments during the trial, such as other chemotherapy, targeted therapy, hormone therapy, immunotherapy, radiotherapy (except for local symptomatic radiotherapy) or Chinese medicine;
  • Concomitant mental illness;
  • The investigator believes that the subject is not suitable for this clinical study.
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Yueying Zhen, Ph.D. 86-22-2492-9366 zhenyueying@hemay.com.cn

Locations
Layout table for location information
China
Tianjin medical university cancer hoapital Recruiting
Tianjin, China
Contact: Ti Zhang, Ph.D.    86-22-23340123 ext 3094    zhangti@tjmuch.com   
Sponsors and Collaborators
Tianjin Hemay Oncology Pharmaceutical Co., Ltd
Investigators
Layout table for investigator information
Principal Investigator: Ti Zhang, Ph.D. Tianjing medical university cancer hospital
Tracking Information
First Submitted Date  ICMJE June 9, 2019
First Posted Date  ICMJE June 11, 2019
Last Update Posted Date July 2, 2020
Actual Study Start Date  ICMJE January 3, 2019
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 9, 2019)
Number of participants with adverse events [ Time Frame: from baseline until 4 weeks after the study day ]
Number of participants with adverse events
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 9, 2019)
  • Objective response rate [ Time Frame: At screening, every 6 weeks of treatment up to 18 months ]
    Objective response rate (complete response rate + partial response rate) according to RECIST v1.1
  • Clinical benefit rate [ Time Frame: At screening, every 6 weeks of treatment up to 18 months ]
    Clinical benefit rate defined as percentage of patients with stable disease (SD) ≥ 6 months/partial response (PR)/complete response (CR). according to RECIST v1.1
  • Progression Free Survival [ Time Frame: 18 months after treatment initiation ]
    Progression Free Survival defined as the proportion of patients alive and without progression (according to RECIST v1.1 criteria)
  • AUC [ Time Frame: 0, 1, 2, 3, 5, 8, 12, 24, 48 and 72 hours post-dose ]
    Area under the plasma concentration versus time curve of Hemay102
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase I Study of Hemay102 in Patients With Advanced Solid Tumors
Official Title  ICMJE A Dose Escalation Phase I Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Antitumor Efficacy of Hemay102 in Patients With Advanced Solid Tumors
Brief Summary This trial was a single-center, open-label, dose-increasing Phase I clinical study with subjects enrolled in patients with advanced solid tumors who failed standard treatment or who were unable to receive effective treatment. The trial is divided into two stages: dose escalation and dose extension.
Detailed Description

Dose escalation:

A total of 7 dosage groups were set at this stage, which were 5 mg/m2, 10 mg/m2, 20 mg/m2, 40 mg/m2, 60 mg/m2, 90 mg/m2, and 120 mg/m2, respectively. Accelerated dosage titration was performed in the first 3 dose groups, 1 subject was enrolled in each group; the last 4 dose groups were perfromed into dosage groups by the principle of "3+3" dose increment rule, and the number of subjects enrolled in each group is 3 to 6 cases.

Dose extension:

According to the test results of the dose escalation phase, two extensions of MTD (tentative 60 mg/m2, 90 mg/m2) were selected for the expansion trial. Each dose level was planned to enroll 6 subjects (12 in total), subjects were administered once every 3 weeks (1 treatment cycle every 3 weeks), and received 4 treatment cycles in a row for Hemay102. Safety, tolerability, pharmacokinetic characteristics, and initial anti-tumor efficacy were evaluated.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Masking Description:
open-label
Primary Purpose: Treatment
Condition  ICMJE Patients With Advanced Stage Solid Tumors
Intervention  ICMJE Drug: Hemay102
Hemay102 was administered through i.v. infusion for 4hrs.
Study Arms  ICMJE
  • Experimental: Hemay102 at the dosage of 5mg/m2
    Hemay102 will be administered to patients through i.v. drip for 4hrs at the dosage of 5mg/m2.
    Intervention: Drug: Hemay102
  • Experimental: Hemay102 at the dosage of 10mg/m2
    Hemay102 will be administered to patients through i.v. drip for 4hrs at the dosage of 10mg/m2.
    Intervention: Drug: Hemay102
  • Experimental: Hemay102 at the dosage of 20mg/m2
    Hemay102 will be administered to patients through i.v. drip for 4hrs at the dosage of 20mg/m2.
    Intervention: Drug: Hemay102
  • Experimental: Hemay102 at the dosage of 40mg/m2
    Hemay102 will be administered to patients through i.v. drip for 4hrs at the dosage of 40mg/m2.
    Intervention: Drug: Hemay102
  • Experimental: Hemay102 at the dosage of 60mg/m2
    Hemay102 will be administered to patients through i.v. drip for 4hrs at the dosage of 60mg/m2.
    Intervention: Drug: Hemay102
  • Experimental: Hemay102 at the dosage of 90mg/m2
    Hemay102 will be administered to patients through i.v. drip for 4hrs at the dosage of 90mg/m2.
    Intervention: Drug: Hemay102
  • Experimental: Hemay102 at the dosage of 120mg/m2
    Hemay102 will be administered to patients through i.v. drip for 4hrs at the dosage of 120mg/m2.
    Intervention: Drug: Hemay102
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 9, 2019)
39
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age ≥18 years old and ≤70 years old, male or female;
  • A patient who has been confirmed by histology or cytology to have advanced or metastatic solid tumors (in the patients with locally advanced hepatocellular carcinoma or metastatic liver cancer, patients can be recruited by clinical diagnosis) and who have failed standard treatment or who are unable to receive/do not have effective treatment;
  • At least one evaluable tumor lesion (spiral CT scan with a long diameter ≥ 10 mm, in accordance with RECIST version 1.1);
  • ECOG PS score 0~1 within 1 week before enrollment;
  • Estimated survival time of more than 3 months;
  • Appropriate hematopoietic function: white blood cell count ≥ 3 × 10^9 / L; absolute neutrophil count ≥ 1.5 × 10^9 / L; platelet count ≥ 100 × 10^9 / L; hemoglobin ≥ 90 g / L;
  • Appropriate liver function: total bilirubin ≤ 1.5 × upper limit of normal (ULN); aspartate transferase (AST) ≤ 2.5 × ULN; alanine aminotransferase (ALT) ≤ 2.5 × ULN;
  • Proper renal function: serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL / min according to the Cockcroft-Gault formula;
  • For clinically confirmed unresectable locally advanced hepatocellular carcinoma or metastatic liver cancer, the patient's liver function must meet the criteria below: ALT≤2.5×ULN, AST≤2.5×ULN, TBIL≤1.5×ULN, Child-Pugh score A or B Grade (≤7 points), blood ammonia ≤100μmol/L (only for patients with hepatocellular carcinoma);
  • A qualified male or female patient with fertility must agree to use a reliable method of contraception (hormone or barrier method) after signing the informed consent until at least 12 weeks after the last dose;
  • Subjects must give informed consent to the study prior to the trial and voluntarily sign a written informed consent form;
  • Subjects are able to communicate well with the investigator and are able to complete the study in accordance with the trial regulations.

Exclusion Criteria:

  • Subjects known to have or suspected to have brain metastases;
  • Have received radiation therapy within 4 weeks before enrollment;
  • Drugs that may affect the metabolism of this product, such as CYP3A4 strong inducer (rifampicin, carbamazepine, phenytoin, etc.) or strong inhibitors (clarithromycin, protease, triazole antifungals, etc.), should be combined within 2 weeks before the study or during the study period;
  • Patients who have previously received anthracycline treatment; or who are known to have a history of allergies to anthracyclines (eg, doxorubicin, epirubicin);
  • Have active infection or HIV-positive infection or other serious illness;
  • Untreated active hepatitis C (anti-HCV antibody positive and HCV RNA positive patients cannot be enrolled); untreated active hepatitis B (HBsAg positive and HBV DNA ≥ 2000 IU/mL) (Note: Hepatitis B subjects treated with treatment also met the inclusion criteria if the following criteria were met: HBV viral load was less than 2000 IU/mL before the first dose of study drug, or patients who are on HBV treatment, and patients with viral load lower than 2000 IU/mL can also be enrolled);
  • Uncontrolled or important cardiovascular disease, which included a) New York Heart Association (NYHA) grade II or higher congestive heart failure, unstable angina, myocardial infarction, or arrhythmia requiring treatment (including atrial fibrillation, at screening) within 6 months prior to the first study drug administration Supraventricular tachycardia, ventricular tachycardia or ventricular fibrillation, or left ventricular ejection fraction (LVEF) < 50%; b) Primary cardiomyopathy (eg dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, undetermined cardiomyopathy); c) Clinically significant QTc interval prolongation history, or screening period QTc interval (corrected by Bazette) ≥ 450ms (male) or ≥ 470ms (female); d) Coronary heart disease with symptoms requiring medication; e) Uncontrollable hypertension (refers to post-treatment systolic blood pressure > 160 mmHg and / or diastolic blood pressure > 100 mmHg);
  • A history of hemorrhagic or thromboembolic events in the past 6 months, such as cerebrovascular accidents (including transient ischemic attacks), pulmonary embolism, and spontaneous bleeding of the tumor;
  • Medical treatment for other clinical trials within 4 weeks prior to enrollment;
  • <4 weeks after major surgery or trauma after enrollment;
  • Must take other treatments during the trial, such as other chemotherapy, targeted therapy, hormone therapy, immunotherapy, radiotherapy (except for local symptomatic radiotherapy) or Chinese medicine;
  • Concomitant mental illness;
  • The investigator believes that the subject is not suitable for this clinical study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Yueying Zhen, Ph.D. 86-22-2492-9366 zhenyueying@hemay.com.cn
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03982303
Other Study ID Numbers  ICMJE HM102ST1S01
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Tianjin Hemay Oncology Pharmaceutical Co., Ltd
Study Sponsor  ICMJE Tianjin Hemay Oncology Pharmaceutical Co., Ltd
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Ti Zhang, Ph.D. Tianjing medical university cancer hospital
PRS Account Tianjin Hemay Oncology Pharmaceutical Co., Ltd
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP