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

Phase 2

• Conditions: Advanced Hepatocellular Carcinoma
• Interventions: Drug: Anlotinib and Sintilimab injection

• Registration Number: NCT04052152
• Lead Sponsor: The First Affiliated Hospital with Nanjing Medical University

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.

Detailed Description

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.

Study Timeline

• Study Start: 2019-06-10
• Status Verified: 2019-07
• Study First Submitted: 2019-07-16
• Study First Submitted QC: 2019-08-08
• Last Update Submitted: 2019-08-08
• Study First Posted: 2019-08-09
• Last Update Posted: 2019-08-09
• Primary Completion: 2019-12-30
• Study Completion: 2021-12-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Not provided

Exclusion Criteria

1. 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.
2. Pregnant or lactating women.
3. 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.
4. Inability to swallow, chronic diarrhea and intestinal obstruction significantly affect drug use and absorption.
5. 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.
6. Coagulation dysfunction (PT > 16 s, APTT > 43 s, TT > 21 s, Fbg < 2 g/L), with bleeding tendency or undergoing thrombolysis or anticoagulation therapy.
7. Have a history of mental illness or psychotropic drug abuse.
8. Peritoneal effusion with clinical symptoms requires therapeutic abdominal puncture or drainage. Or patients with hepatic encephalopathy as well as with liver transplantation.
9. Patients with cancer thrombus involving the main portal vein or inferior vena cava.
10. Patients with Infectious pneumonia, non-infectious pneumonia, interstitial pneumonia and other disease requiring corticosteroids.
11. A history of chronic autoimmune diseases, such as systemic lupus erythematosus.
12. 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.
13. Patients with a history of sarcoidosis or tuberculosis.
14. 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.
15. Patients who are allergic to components of Sintilimab injection and anlotinib preparations, or have a history of severe allergic reactions to other monoclonal antibodies.
16. Having a history of psychotropic substance abuse and being unable to quit or having a mental disorder.
17. Patients with a history of immunodeficiency, or other acquired congenital immunodeficiency diseases, or a history of organ transplantation and hematopoietic stem cell transplantation.
18. First dose immunosuppressive drugs used in the first 4 weeks, not including the nasal spray, inhalation, or other ways of topical corticosteroids or physiological doses of systemic corticosteroids (no more than 10 mg/day prednisone or other equivalent dose glucocorticoids). But temporary use of glucocorticoids is permitted for the treatment of dyspnea symptoms of asthma, chronic obstructive pulmonary disease and other diseases.
19. Systemic immunostimulant therapy was administered within 4 weeks prior to first administration or planned during the study period. Or systemic immunostimulant therapy was received within 4 weeks.
20. According to the researchers' judgment, there are serious concomitant diseases that endanger patient safety or prevent patients from completing the study.
21. Drug combinations that have an effect on the metabolism of CYP3A.
22. Urinary protein 2+ or 24-hour urinary protein >1g.
23. Central nervous system metastasis has occurred.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Group A	Anlotinib and Sintilimab injection	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

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	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	the best Objective Response Rate
Adverse reaction 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	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.

Secondary Outcome Measures

Name	Time	Method
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	Progression Free Survival
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	Duration of Response
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	the Rate of Disease Control
Overall survival (OS)	From date of randomization until the date of patient died, assessed up to 24 months	Overall Survival

Trial Locations

Locations (1)

Jiangsu Province Hospital; 🇨🇳 Nanjing, Jiangsu, China