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Dual TORC1/TORC2 Inhibitor ATG-008 (CC-223) in HBV Positive Advanced Hepatocellular Carcinoma (HCC) Subjects

Primary Purpose

Hepatocellular Carcinoma

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ATG-008
Sponsored by
Antengene Therapeutics Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring HCC

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male or female aged from 18 to 70 years (inclusive) at the time when the ICF is signed.
  2. Confirmed diagnosis of HCC.
  3. Unresectable stage B or C HCC according to the Barcelona Clinic Liver Cancer (BCLC) staging.
  4. HBV positive by serum test.
  5. Received at least one prior line of systemic therapy.
  6. ECOG performance status score of 0 or 1.
  7. Satisfactory serum chemistry results
  8. Adequate bone marrow function
  9. Child-Pugh A without encephalopathy.
  10. All subjects who participated in the study had to take reliable contraceptive measures within the trial and 3 months of after the trial.

Exclusion Criteria:

  1. Symptomatic central nervous system metastases.
  2. Locoregional HCC therapy, systemic chemotherapy, hormonal therapy or investigational therapy within 4 weeks prior to Screening.
  3. Life expectancy of less than 3 months.
  4. Prior therapy with mTOR inhibitors.
  5. Prior organ transplant.
  6. Persistent diarrhea or malabsorption.
  7. Clinically significant bleeding.
  8. Known history of human immunodeficiency virus (HIV) infection.
  9. Uncontrolled intercurrent illness.
  10. Any condition that confounds the ability to interpret data from the trial.

Sites / Locations

  • Oncology Hospital of Haerbin Medical University
  • China People PLA 81 Hospital
  • West China Hospital Sichuan University
  • Yunnan Cancer Hospital
  • The first Hospital of Jilin University
  • Hunan Province Oncology Hospital
  • Daping Hospital
  • The first hospital of Chongqing medical university
  • Xiehe Hospital of Fujian Medical University
  • Nanfang Hospital of Nanfang Medical University
  • The first affiliated Hospital of Zhejiang University
  • Zhejiang Province Oncology Hospital
  • The first affiliated hospital of Anhui medical university
  • The second affiliated hospital of Anhui medical university
  • The first affiliated hospital of Guangxi Medical University
  • Oncology Hospital of Fudan University
  • Zhongshan Hospital of Fudan University
  • General Hospital of the Northern War Zone of the Chinese People's Liberation Army
  • Tangdu Hospital of China PLA fourth medical university
  • Dong-A University Hospital
  • Pusan National Univ. Hospital
  • Kyungpook National Univ. Hospital
  • Asan Medical Center
  • Seoul National University Hospital
  • Severance Hospital, Yonsei University Health System
  • China Medical University Hospital
  • National Taiwan University Hospital
  • Taipei Medical University Hospital
  • Taipei Veterans General Hospital
  • Chang Gung Memorial Hospital-Linkuo

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ATG-008

Arm Description

To enroll approximately 40 hepatitis B virus (HBV) positive, unresectable HCC subjects who have previously received at least one prior line of systemic therapy. Among which, approximately 20 subjects will receive oral ATG-008 at an initial dose of 45 mg, once daily (QD) and another approximately 20 subjects will receive oral ATG-008 at an initial dose of 20 mg, twice daily (BID). The pharmacokinetic (PK) samples will be collected from 10 subjects each in the two dose groups.

Outcomes

Primary Outcome Measures

Cmax
Peak Plasma Concentration (Cmax)
AUC
Area under the plasma concentration versus time curve (AUC)
The incidence of treatment emergent adverse events (TEAEs) & SAE assessed by CTCAE v4.03
The treatment emergent adverse events (TEAEs) & SAE case No. in total subject No.
ORR
Percentage of subjects with PR, or CR

Secondary Outcome Measures

OS
Kaplan-Meier estimate of Overall Survival
TTP
The time from the first dose date until disease progression
PFS
The time from the first dose date until disease progression or death from any cause
DCR
The percentage of subjects with CR, or PR or stable disease (SD)
DOR
The time from the criteria are first met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented
TTR
The time from the first dose date to the first documentation of response of PR or better.
6, 9 and 12 month of survival rate
Percentage of patients alive

Full Information

First Posted
June 20, 2018
Last Updated
July 6, 2023
Sponsor
Antengene Therapeutics Limited
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1. Study Identification

Unique Protocol Identification Number
NCT03591965
Brief Title
Dual TORC1/TORC2 Inhibitor ATG-008 (CC-223) in HBV Positive Advanced Hepatocellular Carcinoma (HCC) Subjects
Official Title
An Open-label Phase 2 Trial of Dual TORC1/TORC2 Inhibitor ATG-008 in HBV+ Advanced Hepatocellular Carcinoma (HCC) Subjects Who Have Received at Least One Prior Line of Systemic Therapy (TORCH)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Terminated
Why Stopped
Based on the adjustment of clinical research and development strategy，sponsor decided to terminate the study
Study Start Date
August 7, 2018 (Actual)
Primary Completion Date
August 3, 2022 (Actual)
Study Completion Date
August 3, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Antengene Therapeutics Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is an Asian multi-regional clinical trial (MRCT) in which ATG-008 will be administered orally to hepatitis B positive (HBV+) HCC subjects who have received at least one prior line of systemic therapy. It is designed as an open-label phase 2 trial evaluating the pharmacokinetics (PK), safety, tolerability and efficacy of oral ATG-008 administered daily until the radiologic disease progression (according to RECIST 1.1) or intolerable toxicity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
HCC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
73 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ATG-008
Arm Type
Experimental
Arm Description
To enroll approximately 40 hepatitis B virus (HBV) positive, unresectable HCC subjects who have previously received at least one prior line of systemic therapy. Among which, approximately 20 subjects will receive oral ATG-008 at an initial dose of 45 mg, once daily (QD) and another approximately 20 subjects will receive oral ATG-008 at an initial dose of 20 mg, twice daily (BID). The pharmacokinetic (PK) samples will be collected from 10 subjects each in the two dose groups.
Intervention Type
Drug
Intervention Name(s)
ATG-008
Intervention Description
Approximately 20 subjects will receive oral ATG-008 at an initial dose of 45 mg/QD and another 20 subjects will receive oral ATG-008 at an initial dose of 20mg/BID for 28 days each cycle.
Primary Outcome Measure Information:
Title
Cmax
Description
Peak Plasma Concentration (Cmax)
Time Frame
Day 1 - Day 15
Title
AUC
Description
Area under the plasma concentration versus time curve (AUC)
Time Frame
Day 1 - Day 15
Title
The incidence of treatment emergent adverse events (TEAEs) & SAE assessed by CTCAE v4.03
Description
The treatment emergent adverse events (TEAEs) & SAE case No. in total subject No.
Time Frame
365 DAYS
Title
ORR
Description
Percentage of subjects with PR, or CR
Time Frame
365 DAYS
Secondary Outcome Measure Information:
Title
OS
Description
Kaplan-Meier estimate of Overall Survival
Time Frame
365 DAYS
Title
TTP
Description
The time from the first dose date until disease progression
Time Frame
365 DAYS
Title
PFS
Description
The time from the first dose date until disease progression or death from any cause
Time Frame
365 DAYS
Title
DCR
Description
The percentage of subjects with CR, or PR or stable disease (SD)
Time Frame
365 DAYS
Title
DOR
Description
The time from the criteria are first met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented
Time Frame
365 DAYS
Title
TTR
Description
The time from the first dose date to the first documentation of response of PR or better.
Time Frame
365 DAYS
Title
6, 9 and 12 month of survival rate
Description
Percentage of patients alive
Time Frame
365 DAYS
Other Pre-specified Outcome Measures:
Title
Potential biomarkers in plasma and tumor tissues
Description
The changes in potential biomarkers including but not limited to TORC1/TORC2 activity in peripheral blood samples and tumor tissue following treatment with ATG-008
Time Frame
365 DAYS
Title
Additional metabolites of ATG-008 in plasma and urine
Description
Additional metabolites of ATG-008 in plasma and urine, and the extent of their urinary excretion/clearance
Time Frame
Day 1 - Day 15

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female aged from 18 to 70 years (inclusive) at the time when the ICF is signed. Confirmed diagnosis of HCC. Unresectable stage B or C HCC according to the Barcelona Clinic Liver Cancer (BCLC) staging. HBV positive by serum test. Received at least one prior line of systemic therapy. ECOG performance status score of 0 or 1. Satisfactory serum chemistry results Adequate bone marrow function Child-Pugh A without encephalopathy. All subjects who participated in the study had to take reliable contraceptive measures within the trial and 3 months of after the trial. Exclusion Criteria: Symptomatic central nervous system metastases. Locoregional HCC therapy, systemic chemotherapy, hormonal therapy or investigational therapy within 4 weeks prior to Screening. Life expectancy of less than 3 months. Prior therapy with mTOR inhibitors. Prior organ transplant. Persistent diarrhea or malabsorption. Clinically significant bleeding. Known history of human immunodeficiency virus (HIV) infection. Uncontrolled intercurrent illness. Any condition that confounds the ability to interpret data from the trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen Xie, PhD
Organizational Affiliation
Medical Monitor
Official's Role
Study Director
Facility Information:
Facility Name
Oncology Hospital of Haerbin Medical University
City
Harbin
State/Province
Heilongjiang
ZIP/Postal Code
150000
Country
China
Facility Name
China People PLA 81 Hospital
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210000
Country
China
Facility Name
West China Hospital Sichuan University
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China
Facility Name
Yunnan Cancer Hospital
City
Kunming
State/Province
Yunnan
ZIP/Postal Code
650118
Country
China
Facility Name
The first Hospital of Jilin University
City
Changchun
Country
China
Facility Name
Hunan Province Oncology Hospital
City
Changsha
Country
China
Facility Name
Daping Hospital
City
Chongqing
Country
China
Facility Name
The first hospital of Chongqing medical university
City
Chongqing
Country
China
Facility Name
Xiehe Hospital of Fujian Medical University
City
Fuzhou
Country
China
Facility Name
Nanfang Hospital of Nanfang Medical University
City
Guangzhou
Country
China
Facility Name
The first affiliated Hospital of Zhejiang University
City
Hangzhou
Country
China
Facility Name
Zhejiang Province Oncology Hospital
City
Hangzhou
Country
China
Facility Name
The first affiliated hospital of Anhui medical university
City
Hefei
Country
China
Facility Name
The second affiliated hospital of Anhui medical university
City
Hefei
Country
China
Facility Name
The first affiliated hospital of Guangxi Medical University
City
Nanning
Country
China
Facility Name
Oncology Hospital of Fudan University
City
Shanghai
Country
China
Facility Name
Zhongshan Hospital of Fudan University
City
Shanghai
Country
China
Facility Name
General Hospital of the Northern War Zone of the Chinese People's Liberation Army
City
Shenyang
Country
China
Facility Name
Tangdu Hospital of China PLA fourth medical university
City
Xi'an
Country
China
Facility Name
Dong-A University Hospital
City
Busan
Country
Korea, Republic of
Facility Name
Pusan National Univ. Hospital
City
Busan
Country
Korea, Republic of
Facility Name
Kyungpook National Univ. Hospital
City
Daegu
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
Country
Korea, Republic of
Facility Name
Severance Hospital, Yonsei University Health System
City
Seoul
Country
Korea, Republic of
Facility Name
China Medical University Hospital
City
Taichung
Country
Taiwan
Facility Name
National Taiwan University Hospital
City
Taipei
Country
Taiwan
Facility Name
Taipei Medical University Hospital
City
Taipei
Country
Taiwan
Facility Name
Taipei Veterans General Hospital
City
Taipei
Country
Taiwan
Facility Name
Chang Gung Memorial Hospital-Linkuo
City
Taoyuan
Country
Taiwan

12. IPD Sharing Statement

Plan to Share IPD
No

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Dual TORC1/TORC2 Inhibitor ATG-008 (CC-223) in HBV Positive Advanced Hepatocellular Carcinoma (HCC) Subjects

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