Clinical trial NCT03591965: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Keywords: HCC
Lead sponsor: Antengene Corporation
Sponsor class: INDUSTRY
First posted: 2018-07-19
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Cmax
timeFrame: Day 1 - Day 15
measure: AUC
timeFrame: Day 1 - Day 15
measure: The incidence of treatment emergent adverse events (TEAEs) & SAE assessed by CTCAE v4.03
timeFrame: 365 DAYS
measure: ORR
timeFrame: 365 DAYS
Secondary outcomes:
measure: OS
timeFrame: 365 DAYS
measure: TTP
timeFrame: 365 DAYS
measure: PFS
timeFrame: 365 DAYS
measure: DCR
timeFrame: 365 DAYS
measure: DOR
timeFrame: 365 DAYS
measure: TTR
timeFrame: 365 DAYS
measure: 6, 9 and 12 month of survival rate
timeFrame: 365 DAYS
Other outcomes:
measure: Potential biomarkers in plasma and tumor tissues
timeFrame: 365 DAYS
measure: Additional metabolites of ATG-008 in plasma and urine
timeFrame: Day 1 - Day 15
Locations:
city: Harbin
country: China
facility: Oncology Hospital of Haerbin Medical University
state: Heilongjiang
city: Nanjing
country: China
facility: China People PLA 81 Hospital
state: Jiangsu
city: Chengdu
country: China
facility: West China Hospital Sichuan University
state: Sichuan
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
city: Changchun
country: China
facility: The first Hospital of Jilin University
city: Changsha
country: China
facility: Hunan Province Oncology Hospital
city: Chongqing
country: China
facility: Daping Hospital
city: Chongqing
country: China
facility: The first hospital of Chongqing medical university
city: Fuzhou
country: China
facility: Xiehe Hospital of Fujian Medical University
city: Guangzhou
country: China
facility: Nanfang Hospital of Nanfang Medical University
city: Hangzhou
country: China
facility: The first affiliated Hospital of Zhejiang University
city: Hangzhou
country: China
facility: Zhejiang Province Oncology Hospital
city: Hefei
country: China
facility: The first affiliated hospital of Anhui medical university
city: Hefei
country: China
facility: The second affiliated hospital of Anhui medical university
city: Nanning
country: China
facility: The first affiliated hospital of Guangxi Medical University
city: Shanghai
country: China
facility: Oncology Hospital of Fudan University
city: Shanghai
country: China
facility: Zhongshan Hospital of Fudan University
city: Shenyang
country: China
facility: General Hospital of the Northern War Zone of the Chinese People's Liberation Army
city: Xi'an
country: China
facility: Tangdu Hospital of China PLA fourth medical university
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National Univ. Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National Univ. Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital-Linkuo
Study officials:
affiliation: Medical Monitor
name: Stephen Xie, PhD
role: STUDY_DIRECTOR
References: