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

Hepatocellular Carcinoma Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03591965
• Other study ID #: ATG-008-HCC-001
• Status: Terminated
• Phase: Phase 2
• Start date: August 7, 2018
• Est. completion date: August 3, 2022

Study information

• Verified date: January 2023
• Source: Antengene Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 73
• Est. completion date: August 3, 2022
• Est. primary completion date: August 3, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• ATG-008
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.

Locations

Country	Name	City	State
China	The first Hospital of Jilin University	Changchun
China	Hunan Province Oncology Hospital	Changsha
China	West China Hospital Sichuan University	Chengdu	Sichuan
China	Daping Hospital	Chongqing
China	The first hospital of Chongqing medical university	Chongqing
China	Xiehe Hospital of Fujian Medical University	Fuzhou
China	Nanfang Hospital of Nanfang Medical University	Guangzhou
China	The first affiliated Hospital of Zhejiang University	Hangzhou
China	Zhejiang Province Oncology Hospital	Hangzhou
China	Oncology Hospital of Haerbin Medical University	Harbin	Heilongjiang
China	The first affiliated hospital of Anhui medical university	Hefei
China	The second affiliated hospital of Anhui medical university	Hefei
China	Yunnan Cancer Hospital	Kunming	Yunnan
China	China People PLA 81 Hospital	Nanjing	Jiangsu
China	The first affiliated hospital of Guangxi Medical University	Nanning
China	Oncology Hospital of Fudan University	Shanghai
China	Zhongshan Hospital of Fudan University	Shanghai
China	General Hospital of the Northern War Zone of the Chinese People's Liberation Army	Shenyang
China	Tangdu Hospital of China PLA fourth medical university	Xi'an
Korea, Republic of	Dong-A University Hospital	Busan
Korea, Republic of	Pusan National Univ. Hospital	Busan
Korea, Republic of	Kyungpook National Univ. Hospital	Daegu
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Medical University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital-Linkuo	Taoyuan

Sponsors (1)

Lead Sponsor	Collaborator
Antengene Therapeutics Limited

Countries where clinical trial is conducted

China,  Korea, Republic of,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Potential biomarkers in plasma and tumor tissues	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	365 DAYS
Other	Additional metabolites of ATG-008 in plasma and urine	Additional metabolites of ATG-008 in plasma and urine, and the extent of their urinary excretion/clearance	Day 1 - Day 15
Primary	Cmax	Peak Plasma Concentration (Cmax)	Day 1 - Day 15
Primary	AUC	Area under the plasma concentration versus time curve (AUC)	Day 1 - Day 15
Primary	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.	365 DAYS
Primary	ORR	Percentage of subjects with PR, or CR	365 DAYS
Secondary	OS	Kaplan-Meier estimate of Overall Survival	365 DAYS
Secondary	TTP	The time from the first dose date until disease progression	365 DAYS
Secondary	PFS	The time from the first dose date until disease progression or death from any cause	365 DAYS
Secondary	DCR	The percentage of subjects with CR, or PR or stable disease (SD)	365 DAYS
Secondary	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	365 DAYS
Secondary	TTR	The time from the first dose date to the first documentation of response of PR or better.	365 DAYS
Secondary	6, 9 and 12 month of survival rate	Percentage of patients alive	365 DAYS