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

NCT04273100 | Unknown Phase 2

• 1 other identifier: PLTHCC
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

The vast majority of primary liver cancer (90%) is hepatocellular carcinoma (HCC), and the majority of HCC patients have been locally advanced or metastatic disease when they are diagnosed in clinics. Most of them are not suitable for radical treatment. In the case of supportive treatment, the median survival time was only 7.9 months. 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, middle and late stage (BCLC-B and BCLC-C) HCC patients. Through the combination of immunotherapy (PD-1 monoclonal antibody), local therapy (TACE) and anti-angiogenic therapy (lenvatinib), 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 middle and late stage HCC.

Conditions

Hepatocellular Carcinoma Non-resectable

Keywords

Hepatocellular carcinoma; Immune Suppression; Angiogenesis; Hepatic Artery Embolism

Outcome Measures

Primary Outcomes (1)

• 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 month

Secondary Outcomes (5)

• 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

• overall survival

  1 year

Other Outcomes (1)

• conversion rate of hepatectomy

  1 year

Study Arms (1)

Treatment group

EXPERIMENTAL

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

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

Interventions

PD-1 mAb combined with TACE and lenvatinib COMBINATION_PRODUCT

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

Treatment group

Eligibility Criteria

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

You may qualify if:

• HCC confirmed by histology / cytology.
• Age ≥ 18 years old.
• Eastern Cooperative Oncology Group (ECOG) physical state score 0 or 1.
• 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, or who have received treatment but PD or SD ≥ 4 weeks.
• Patients who had not received TACE before the first administration, or who had received TACE but SD ≥ 4 weeks.
• According to RECIST v1.1, 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.
• 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).
• Serious bleeding tendency or coagulation dysfunction, or undergoing thrombolysis.
• In the past 6 months, there was a history of gastrointestinal perforation and / or fistula, a history of intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive enterotomy (partial colectomy or extensive enterotomy with chronic diarrhea), Crohn's disease, ulcerative colitis or long-term chronic diarrhea.
• Received radiotherapy within 3 weeks before the first administration. For patients who received radiotherapy three weeks before the first administration, all the following conditions must be met before entering the group: at present, there is no toxic reaction related to radiotherapy, no need to take glucocorticoids, excluding radiation pneumonia, radiation hepatitis, radiation enteritis, etc.
• Previous and current pulmonary fibrosis history, interstitial pneumonia, pneumoconiosis, drug-related pneumonia, severe impairment of lung function and other lung diseases.

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (1)

Tianjin Medical University Cancer Hospital

Tianjin, Tianjin Municipality, 300060, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

lenvatinib

Condition Hierarchy (Ancestors)

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

Study Design

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

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

Study Record Dates

• First Submitted: January 28, 2020
• First Posted: February 17, 2020
• Study Start: November 14, 2019
• Primary Completion: December 31, 2020
• Study Completion: June 30, 2021
• Last Updated: February 17, 2020

Record last verified: 2020-01

Locations

CN (1)