Regorafenib Combined With PD-1 Inhibitor Therapy for Second-line Treatment of Hepatocellular Carcinoma

NCT05048017 | Unknown Phase 2

• 1 other identifier: JS-3039
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm, nonrandomized, single center clinical study to investigate the safety and efficacy of regorafenib combined with PD-1 inhibitor therapy for second-line treatment of hepatocellular carcinoma

Conditions

Hepatocellular Carcinoma; Regorafenib; PD-1 Inhibitor

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  A duration from the date of initial treatment to disease progression (defined by RECIST 1.1) or death of any cause

  one year

Secondary Outcomes (8)

• Objective Response Rate (ORR)

  one year

• Complete response (CR)

  one year

• Partial response (PR)

  one year

• Overall survival (OS)

  one year

• Duration of response (DOR)

  one year

Other Outcomes (2)

• Adverse Event (AE)

  two years

• Adverse Drug Reaction (ADR)

  two years

Study Arms (1)

Regorafenib plus PD-1 inhibitor

EXPERIMENTAL

Regorafenib (BAY 73-4506, Stivarga®) is an oral diphenylurea multi-kinase inhibitor that targets angiogenic (VEGFR1-3, TIE2), stromal (PDGFR-β, FGFR), and oncogenic receptor tyrosine kinases (KIT, RET, and RAF). Camrelizumab (AiRuiKa™), a programmed cell death 1 (PD-1) inhibitor being developed by Jiangsu Hengrui Medicine Co. Ltd, recently received conditional approval in China for the treatment of relapsed or refractory classical Hodgkin lymphoma. Toripalimab, a recombinant, humanized programmed death receptor-1 (PD-1) monoclonal antibody that binds to PD-1 and prevents binding of PD-1 with programmed death ligands 1 (PD-L1) and 2 (PD-L2), is being developed by Shanghai Junshi Bioscience Co., Ltd in China for the treatment of various cancers. Pembrolizumab (Keytruda) the programmed cell death protein 1 (PD1) is one of the checkpoints that regulates the immune response. Ligation of PD1 with its ligands PDL1 and PDL2 results in transduction of negative signals to T-cells.

Drug: Regorafenib; Drug: PD-1 inhibitor

Interventions

Regorafenib DRUG

Regorafenib, 120 mg, once a day, 3 weeks on/1 week off

Also known as: BAY 73-4506, Stivarga

Regorafenib plus PD-1 inhibitor

PD-1 inhibitor DRUG

Camrelizumab: 200mg (BW ≥ 50 kg) or 3 mg/kg (BW \< 50 kg) Toripalimab: 240mg is given through intravenous drip every 3 weeks on Day 1 of each course of treatment. Pembrolizumab: 200mg is given through intravenous drip every 3 weeks.

Also known as: Camrelizumab (AiRuiKa™)、Toripalimab、Pembrolizumab(Keytruda)

Regorafenib plus PD-1 inhibitor

Eligibility Criteria

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

You may qualify if:

• Subject must meet all of the following criteria to be enrolled in the study:
• Subjects volunteer to participate in the study, agree to sign their written informed consent, show good compliance and are cooperative with the follow-up.
• There is no gender requirement but age requirement (age\>18) for the subjects who sign the informed consent.
• The subjects were diagnosed as advanced hepatocellular carcinoma (HCC) by imaging or histological examination.
• The disease is not suitable for radical surgery and/or local treatment, or disease progression occurs after surgery and/or local treatment.
• The patients with at least one measurable lesion according to RECIST, version1.1, and no local radiotherapy was performed. Results of spiral CT scan (RECIST, version 1.1): LD (lesion) ≥ 10 mm or SD (enlarged lymph node) ≥ 15 mm.
• The patients who failed or were intolerable to the following treatments: simple sorafenib therapy, or sorafenib combined with PD-1 therapy, or simple lenvatinib therapy, or lenvatinib combined with PD-1 therapy, or bevacizumab combined with atezolizumab.
• Definition of treatment failure: It refers to the disease progression during treatment or the recurrence of the disease after treatment (Obvious disease recurrences and progressions appeared in patients who have received at least one radical or palliative resection, interventional therapy or radiotherapy. The treatment period of systemic chemotherapy like oxaliplatin and other systemic chemotherapy must be at least one cycle. The treatment time of molecular targeted therapy must be longer than 14 days).
• Definition of intolerable: Hematological toxicity ≥ Grade IV, or non-hematological toxicity ≥ Grade III, or damage to the heart, liver, kidney and other major organs ≥ Grade II occurred during the treatment. For details, please refer to the package inserts of each drug.
• The ECOG score within 1 week before enrollment was 0-1 points.
• Child-Pugh score for liver function: Class A, BCLC staging is B-C stage.
• The time from failure of first-line system treatment to enrollment in this study (the time to sign the informed consent form) was ≥ 2 weeks , and the adverse events basically returned to normal (NCI-CTCAE ≤ Grade I).
• The expected survival time is greater than or equal to 6 months.
• HBV DNA \< 2000 IU/ml (104 copies/ml).
• Hematology and organ function are adequate, based on the following laboratory test results obtained within 14 days prior to the start of study treatment (unless otherwise stated):

You may not qualify if:

• Patients meeting one or more of the following conditions cannot be included:
• The clinical stage is stage IV, and/or patients with hepatobiliary solid tumors with any of the following conditions:
• The patient is suitable for surgical radical treatment, 1.2 or, the patient has accepted radical treatment and has no assessable lesion, 1.3 or, the patient has a history of liver transplantation or plans to undergo liver transplantation.
• Patient who is known to be allergic to recombinant humanized PD-1 monoclonal antibody drugs and their components; Patient who is known to be allergic to regorafenib and its components.
• ECOG score ≥ 2 points.
• Patient who has ascites with clinical symptoms, that requires therapeutic abdominal puncture or drainage, or Child-Pugh score \> 2 points.
• Patient with serious heart, cerebrovascular and other systemic diseases with unstable or uncontrollable condition.
• Patient with active central nervous system (CNS) metastasis and/or cancerous meningitis. Subjects with previously treated brain metastases can participate in the study, as long as their brain metastases are stable (imaging shows no evidence of progression for at least four weeks before the first trial treatment and all neurological symptoms have returned to baseline) with no evidence shows new or enlarged brain metastases, and steroids are not used for at least 7 days before the trial treatment. This exception does not include cancerous meningitis, which is excluded regardless of how its clinical stability is.
• Patient who has accepted major surgery within 4 weeks before the first study administration (appropriate wound healing and clinical evaluation must be performed after major surgery, which has nothing to do with the time of enrollment)
• Patient with liver and kidney dysfunction, such as jaundice, ascites, and/or bilirubin \> 2×ULN, and/or alkaline phosphatase ≥ 3×ULN; and/or ≥ Grade 3 (CTC-AE 5.0) persistent proteinuria, creatinine ratio \> 3.5g/24 hours, or renal failure requiring blood or peritoneal dialysis, etc.
• Urine routine test shows urine protein ≥ ++ or confirmed 24-hour urine protein quantification\>1.0g;
• Patient with persistent infection which is greater than Grade 2 (CTC-AE5.0).
• Patient with a history of organ allogeneic transplantation (participants underwent allogeneic tissue/solid organ transplantation)
• Patient with a history of active tuberculosis (TB bacilli)
• Patient intolerance to any study drug (or any excipient)

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Hai-Tao Zhao

Beijing, Beijing Municipality, 100730, China

RECRUITING

Related Publications (19)

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MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

regorafenib; Immune Checkpoint Inhibitors; camrelizumab

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

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Central Study Contacts

Hai-Tao Zhao, PhD

CONTACT

+861069156042; zhaoht@pumch.cn

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: August 17, 2021
• First Posted: September 17, 2021
• Study Start: October 1, 2021
• Primary Completion: November 1, 2025
• Study Completion: December 1, 2025
• Last Updated: March 29, 2023

Record last verified: 2023-01

Locations

CN (1)