TACE, Sorafenib and PD-1 Monoclonal Antibody in the Treatment of HCC

NCT04518852 | Completed Phase 2

• 1 other identifier: GXu
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death that ranks sixth in terms of incident cases, with an overall 5 years survival of 18%. Despite a significant improvement in treatment strategy, the overall survival of HCC remains low due to high recurrence, progressive liver dysfunction and the high fatality of the disease. Surgical resection has been applied in a number of patients; however, surgery has been associated with a high incidence of recurrence (approximately 70% within 5 years). TACE is generally applied on intermediate-stage HCC. However, TACE is not satisfied with improving overall survival. Therefore, there is an urgent need for effective treatment for these patients. At present, the overall objective response rate (ORR) of single or sequential therapy is not satisfied, and the over survival (OS) improvement is not ideal. Therefore, combined therapy maybe the good choice for patients with advanced HCC. This study focuses on the in-operable, BCLC-B/C HCC patients. Through the combination of local therapy (TACE), anti-angiogenic therapy (Sorafenib), and immunotherapy (PD-1 monoclonal antibody), it is expected to change the tumor microenvironment, restore the immune response, strengthen the anti-tumor effect of various treatments, and improve the therapeutic efficacy in patients with BCLC-B/C HCC.

Conditions

Hepatocellular Carcinoma; Liver Neoplasms; Digestive System Neoplasms; Sorafenib; Molecular Mechanisms of Pharmacological Action; Liver Diseases; Antineoplastic Agents; Protein Kinase Inhibitors

Keywords

Hepatic Artery Embolism; Angiogenesis; Immune Suppression

Outcome Measures

Primary Outcomes (2)

• objective response rate (ORR)

  The proportion of patients whose tumor volume reduction reaches the predetermined value and can maintain the minimum time limit. It is the sum of the proportion of complete response (CR) and partial response(PR). That is, ORR = CR + PR

  Change from baseline tumor volume at 6 months

• overall survival (OS)

  the time from the beginning of treatment to death caused by any reason (the last follow-up time is for the patients who lost the visit; the end of the study is for the patients who are still alive)

  1 year

Secondary Outcomes (4)

• progression free survival (PFS)

  Up to 24 months, from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

• time to progression (TTP)

  Up to 24 months, from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

• disease control rate (DCR)

  1 year

• duration of response

  up to 48 weeks

Other Outcomes (1)

• conversion rate of hepatectomy

  1 year

Study Arms (1)

Treatment group

EXPERIMENTAL

The participants will receive the combined treatment of local therapy (TACE, oxaliplatin and epirubicin), anti-angiogenic therapy (sorafenib), and immunotherapy (PD-1 monoclonal antibody)

Combination Product: TACE combined with sorafenib and PD-1 mAb

Interventions

TACE combined with sorafenib and PD-1 mAb COMBINATION_PRODUCT

the combination of local therapy (TACE), anti-angiogenic therapy (sorafenib), and immunotherapy (PD-1 monoclonal antibody)

Treatment group

Eligibility Criteria

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

You may qualify if:

• Histopathologically or clinically confirmed hepatocellular carcinoma.
• Age ≥ 18 years old.
• Performance status (PS) ≤ 2 (ECOG scale).
• Barcelona clinical liver cancer (BCLC) stage B or stage C.
• Participants who have not received other systemic anti-tumor treatment for HCC before the first administration.
• Patients who had not received TACE before the first administration, or who had received 0-2 times TACE but PD or SD ≥ 4 weeks.
• According to mRECIST, there is at least one measurable lesion.
• Child Pugh score ≤ 7.
• Participant has sufficient organ and marrow functions.
• Expected survival time ≥ 12 weeks.
• For women of childbearing age or male patients whose sexual partners are women of childbearing age, effective contraceptive measures should be taken during the whole treatment period and 6 months after the last medication.
• Sign the written informed consent, and be able to follow the visit and relevant procedures specified in the plan

You may not qualify if:

• Fibrolamellar carcinoma, sarcomatoid carcinoma, cholangiocarcinoma and other components previously confirmed by histology / cytology.
• History of hepatic encephalopathy or liver transplantation.
• Pleural effusion, ascites and pericardial effusion with clinical symptoms requiring drainage.
• Tumor burden≥70%, diffuse liver cancer or tumor is not suitable for mRECIST standard evaluation.
• Received local treatment (ablation therapy), surgery resection and radiotherapy for liver cancer before the first administration.
• Have received systemic chemotherapy, targeted therapy or immunotherapy
• There is a significant decrease in white blood cells and platelets in peripheral blood, severe coagulation dysfunction and can not be corrected：the neutrophil\<1.5×109/L, PLT\<50×109/L. The INR\>2.3
• Acute or chronic active hepatitis B or C infection, hepatitis B virus (HBV-DNA) \> 10\^6 copies / ml; hepatitis C virus (HCV-RNA) \> 10\^3 copies / ml; HBsAg and anti HCV antibody were positive at the same time.
• There is central nervous system metastasis.
• Bleeding of esophageal or gastric varices caused by portal hypertension occurred in the past 6 months, or severe (G3) varices were found in endoscopic examination within 3 months before the first administration, or evidence of portal hypertension (including splenomegaly found in imaging examination) was found. The researchers assessed that the risk of bleeding was high and did not receive sclerotherapy or ligation under the endoscope.
• The previous 6-month history of arteriovenous thromboembolism, including myocardial infarction, unstable angina, cerebrovascular accident, pulmonary embolism, deep vein thrombosis or any other serious thromboembolism. The thrombus of implanted vein port or catheter source or superficial vein is stable after routine anticoagulant treatment. Prophylactic use of low- molecular-weight heparin (e.g., enoxaparin 40 mg / day) is permitted.
• Tumor thrombus of main portal vein, or involving superior mesenteric vein at the same time.
• Aspirin (\> 325 mg / day) or other drugs known to inhibit platelet function such as dipyridamole or clopidogrel were used for 7 consecutive days within 2 weeks before the first administration.
• For uncontrolled hypertension, systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 100 mmHg after the best medical treatment, hypertension crisis or hypertension encephalopathy history.
• Symptomatic congestive heart failure (New York Heart Association class II-IV). Symptomatic or poorly controlled arrhythmias. The corrected QT interval (QTc) for the history or screening of congenital long QT syndrome was more than 500 ms (calculated by Fridericia method).

Sponsors & Collaborators

• Sichuan Cancer Hospital and Research Institute: lead

Study Sites (1)

Sichuan Cancer Hospital and Research Institute

Chengdu, Sichuan, 610041, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms; Digestive System Neoplasms; Liver Diseases

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sichuan Cancer Hospital and Research Institute

Model Details: This study focuses on the in-operable, BCLC-B/C stage HCC patients. The participants will receive the combined treatment of local therapy (TACE) , anti-angiogenic therapy (sorafenib), and immunotherapy (PD-1 monoclonal antibody)

Study Record Dates

• First Submitted: August 15, 2020
• First Posted: August 19, 2020
• Study Start: September 14, 2020
• Primary Completion: July 31, 2022
• Study Completion: January 31, 2023
• Last Updated: June 25, 2024

Record last verified: 2024-06

Locations

CN (1)