Anlotinib Hydrochloride Combined With Sintilimab Injection in the Treatment of Advanced Hepatocellular Carcinoma (HCC)

NCT04052152 | Unknown Phase 2 DMC

• 1 other identifier: KEEP-G 04
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, open-label and exploratory clinical study of Anlotinib Hydrochloride Capsules combined with Sintilimab injection in the treatment of advanced Hepatocellular Carcinoma (HCC). In oder to observe and evaluate the efficacy and safety of Anlotinib Hydrochloride Capsules combined with Sintilimab injection. Subjects with pathological confirmed Hepatocellular Carcinoma will be enrolled. 21 days as a treatment cycle, Anlotinib 12mg/day(D1-D14 ) and Sintilimab injection 200mg Q3W (D1). Sintilimab injection will be administered until disease progressioncor un-tolerable toxicity. Anlotinib will be administered until disease progression. If anlotinib is not tolerated, the dose can be reduced to 10mg or 8mg ,until un-tolerable toxicity again.

Conditions

Advanced Hepatocellular Carcinoma

Keywords

HCC; Antiangiogenic agents combined with PD-1 antibody

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR)

  the best Objective Response Rate

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months

• Adverse reaction rate

  Observe all the participants in any adverse events occurred during the period of clinical research, including clinical symptoms and signs of life, an abnormal in laboratory tests, record its clinical characteristics, severity, occurrence time, duration, treatment and prognosis, and determine its and the correlation between test drugs. NCI-CTC AE 5.0 standard was used to evaluate drug safety.

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months

Secondary Outcomes (4)

• Progression Free Survival (PFS)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months

• Duration of Response (DOR)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months

• Disease Control Rate (DCR)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months

• Overall survival (OS)

  From date of randomization until the date of patient died, assessed up to 24 months

Study Arms (1)

Group A

EXPERIMENTAL

Patients in the study group will receive the following treatment: 21 days as a treatment cycle, Anlotinib 12mg/day(D1-D14 ) and Sintilimab injection 200mg Q3W (D1). Sintilimab injection will be administered until disease progressioncor un-tolerable toxicity. Anlotinib will be administered until disease progression. If anlotinib is not tolerated, the dose can be reduced to 10mg or 8mg ,until un-tolerable toxicity again

Drug: Anlotinib and Sintilimab injection

Interventions

Anlotinib and Sintilimab injection DRUG

Patients will be treated with Anlotinib and Sintilimab injection

Group A

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least one measurable lesion (the length of spiral CT scan (\> 10mm) meets the requirements of RESCIST 1.1) is found in patients with HCC confirmed by histopathology or cytology or who meet the clinical diagnostic criteria.
• Inability or unwillingness to undergo surgery and transcatheter hepatic artery interventional therapy; if interventional therapy, radiotherapy or surgery has been accepted, it must be more than 4 weeks, and adverse reactions or wounds have fully recovered.
• No treatment with sorafenib or other systemic treatment was received. Patients who have used interventional chemotherapeutic drugs during interventional therapy may be enrolled in the group.
• Child-Pugh liver function rating: grade A or B; BCLC stage B or C.
• ECOG 0-1
• The life expectancy is more than 12 weeks.
• The main organs are functioning normally.
• Subjects volunteered to join the study, signed informed consent, good compliance, with follow-up.

You may not qualify if:

• Hepatobiliary and mixed cell carcinomas and fiberboard cell carcinomas are known; other malignant tumors (except cured cutaneous basal cell carcinomas and cervical carcinoma in situ) have been reported in the past or at the same time.
• Pregnant or lactating women.
• Patients with hypertension who could not be well controlled by antihypertensive drugs (systolic blood pressure \> 150 mmHg, diastolic blood pressure \> 100 mmHg), patients with myocardial ischemia or myocardial infarction above grade II, arrhythmias with poor control (including QTC interval \> 450 ms) and cardiac insufficiency of grade III-IV according to NYHA standard.
• Inability to swallow, chronic diarrhea and intestinal obstruction significantly affect drug use and absorption.
• There are clear concerns about gastrointestinal bleeding (such as local active ulcer lesions, fecal occult blood ++) or more), and there is a history of gastrointestinal bleeding within 6 months.
• Coagulation dysfunction (PT \> 16 s, APTT \> 43 s, TT \> 21 s, Fbg \< 2 g/L), with bleeding tendency or undergoing thrombolysis or anticoagulation therapy.
• Have a history of mental illness or psychotropic drug abuse.
• Peritoneal effusion with clinical symptoms requires therapeutic abdominal puncture or drainage. Or patients with hepatic encephalopathy as well as with liver transplantation.
• Patients with cancer thrombus involving the main portal vein or inferior vena cava.
• Patients with Infectious pneumonia, non-infectious pneumonia, interstitial pneumonia and other disease requiring corticosteroids.
• A history of chronic autoimmune diseases, such as systemic lupus erythematosus.
• Patients with a history of inflammatory bowel diseases such as ulcerative enteritis and crohn's disease. Or patients with a history of inflammatory chronic diarrheal diseases such as irritable bowel syndrome.
• Patients with a history of sarcoidosis or tuberculosis.
• Patients with active hepatitis b, c and HIV infection; HBVER who could controll HBV DNA\<500 copy/ml after antiviral treatment is allowed to be included.
• Patients who are allergic to components of Sintilimab injection and anlotinib preparations, or have a history of severe allergic reactions to other monoclonal antibodies.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (1)

Jiangsu Province Hospital

Nanjing, Jiangsu, 210029, China

RECRUITING

Related Publications (1)

• Chen X, Li W, Wu X, Zhao F, Wang D, Wu H, Gu Y, Li X, Qian X, Hu J, Li C, Xia Y, Rao J, Dai X, Shao Q, Tang J, Li X, Shu Y. Safety and Efficacy of Sintilimab and Anlotinib as First Line Treatment for Advanced Hepatocellular Carcinoma (KEEP-G04): A Single-Arm Phase 2 Study. Front Oncol. 2022 May 31;12:909035. doi: 10.3389/fonc.2022.909035. eCollection 2022.

  PMID: 35712486 DERIVED

MeSH Terms

Interventions

anlotinib; sintilimab

Study Officials

• Yongqian Shu, PhD

  JANGSU PROVINCE HOSPITAL

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yongqian Shu, PhD

CONTACT

00862568306428; shuyongqian@csco.org.cn

Xiaofeng Chen, PhD

CONTACT

008613585172066; xiaofengch198019@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2019
• First Posted: August 9, 2019
• Study Start: June 10, 2019
• Primary Completion: December 30, 2019
• Study Completion: December 30, 2021
• Last Updated: August 9, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)