Thermal Ablation Combined With Anlotinib and TQB2450 Solution for HCC

Safety and Effectiveness of Thermal Ablation Combined With Anlotinib and TQB2450 Solution for Advanced Hepatocelualr Carcinoma

In this study, investigators aimed to evaluated the efficacy and safety of microwave ablation combined with anlotinib and TQB2450 Solution in patients with advanced hepatocellular carcinoma. Patients were randomly assigned at a one-to-one ratio to receive microwave ablation plus anlotinib and TQB2450 Solution or microwave ablation plus TQB2450 Solution. Primary end points were objective response rate(ORR). Second end points include overall survival, progression-free survival and disease control rate. Safety was assessed in all patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatocellular Carcinoma; Anlotinib; Thermal Ablation; PDL-1
• Intervention / Treatment: Drug: Anlotinib and TQB2450 solution; Drug: TQB2450 solution

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ping Liang; Phone Number: +8601066939530 +8601066939530; Email: liangping301@126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100853
      • Chinese PLA General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. ECOG PS score: 0-1, Life expectancy of 3 months or more
2. Subjects must have confirmed diagnosis of HCC
3. BCLC B and C grade
4. At least 1 measurable target lesion according to mRECIST
5. Child-Pugh score A to B
6. No locoregional therapy within 4 weeks before enrollment for patients with unresectable HCC or tumor progression after locoregional therapy; All toxicities related to prior treatments must be resolved to Grade ≤1
7. No prior treatment with anti-angiogenic drugs or any anti-PD-1 agent within 4 weeks before enrollment
8. HBV DNA<500IU/mL
9. Adequate organ function within 14 days before enrollment
10. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 7 days prior to the start of study drug. Women must not be breastfeeding. Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment
11. Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol

Exclusion Criteria:

1. Prior liver transplant
2. Any prior (within 1 year) or current clinically significant ascites as measured by physical examination and that requires active paracentesis for control
3. Prior treatment with an anti-PD-L1
4. Active autoimmune disease that has required systemic treatment in past 2 years
5. Known or suspected allergy to Anlotinib and TQB2450 Solution or study drug components；History of severe hypersensitivity reaction to any monoclonal antibody
6. Has received a live-virus vaccination within 30 days of planned treatment start.
7. Subjects with CNS metastases are not eligible, unless they have completed local therapy (eg, whole brain radiation therapy [WBRT], surgery or radiosurgery) and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs (eg, radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment
8. Subjects with any active, known, or suspected autoimmune disease； Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
9. HBV DNA ≥ 1000 IU/ml，HCV RNA
10. New York Heart Association congestive heart failure of grade II or above, unstable angina, myocardial infarction within the past 6 months, or serious cardiac arrhythmia associated with significant cardiovascular impairment within the past 6 months, Prolongation of QTc (Fridericia formula) interval to >480 ms
11. Dysfunction of blood coagulation （INR>1.5 or APTT>1.5×ULN）, Bleeding or thrombotic disorders
12. Anticoagulants requiring therapeutic INR monitoring, eg, warfarin or similar agents. Antiplatelet agents and low molecular weight heparin are prohibited throughout the study
13. Active infection (any infection requiring systemic treatment)
14. History of solid organ or hematologic transplant
15. Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anlotinib and TQB2450 solution; Microwave ablation will be performed according to patients' tumor number, size and liver function. Oral anlotinib (12 mg/d) will be administered and its cycle is defined as 2 weeks on-treatment followed by 1 week off-treatment. Patients will be given 1200 mg TQB245 solution intravenously every 3 weeks. The treatment continues until disease progression or treatment intolerance. Anlotinib and TQB2450 solution will be given after 2 weeks of microwave ablation procedure.	Drug: Anlotinib and TQB2450 solution; Anlotinib is a novel multitarget tyrosine kinase inhibitor, inhibiting tumour angiogenesis and proliferative signalling. TQB2450 solution is a new novel of PD-L1 inhibitor made by Crown Bioscience and CHIATAI TIANQING(CTTQ PHARMA).
Active Comparator: TQB2450 Solution; Microwave ablation will be performed according to patients' tumor number, size and liver function. Patients will be given 1200 mg TQB245 solution intravenously every 3 weeks.TQB2450 solution will be given after 2 weeks of microwave ablation procedure.	Drug: TQB2450 solution; TQB2450 solution is a new novel of PD-L1 inhibitor made by Crown Bioscience and CHIATAI TIANQING(CTTQ PHARMA).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Objective Response Rate	2-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall Survival	2-year
PFS	Progression-free Survival	2-year
DCR	Disease Control Rate	2-year
EORTC QLQ C30	Impact of treatment on Health Related Quality of Life (HRQoL) for subjects treated using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire. EORTC QLQ C30 scales were grouped and converted to score 0 to 100 according to the scoring manual; a higher score represents a more severe symptom or problem.	Change from baseline health related quality of life at 2 years
EORTC QLQ-HCC18	Impact of treatment on Health Related Quality of Life (HRQoL) for subjects treated using HCC-specific EORTC QLQ-HCC18 questionnaire. EORTC QLQ-HCC18 scales were grouped and converted to score 0 to 100 according to the scoring manual; a higher score represents a more severe symptom or problem.	Change from baseline health related quality of life at 2 years
AE	Incidence of Adverse Events	2-year
SAEs	Incidence of Severe Adverse Events	2-year

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): March 5, 2021
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: November 30, 2020
• First Submitted That Met QC Criteria: December 7, 2020
• First Posted (Actual): December 11, 2020

Study Record Updates

• Last Update Posted (Actual): March 4, 2021
• Last Update Submitted That Met QC Criteria: March 2, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Pharmaceutical Solutions
• Other Study ID Numbers: 301jrcsk-lp-yj

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No