Trial Title:
Observation Study of Sequential Regorafenib Plus ICIs After HAIC for Advanced Hepatocellular Carcinoma
NCT ID:
NCT05573282
Condition:
Hepatocellular Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Conditions: Keywords:
Hepatic arterial infusion chemotherapy
Regorafenib
Immunocheckpoint inhibitor
Study type:
Observational
Overall status:
Recruiting
Study design:
Time perspective:
Prospective
Intervention:
Intervention type:
Other
Intervention name:
Regorafenib combine with ICIs
Description:
Regorafenib: 80mg/day, PO, QD, d1～d21, Q4W ICIs: 200mg/day, IV, d1,Q3W
Arm group label:
Sequential therapy of Regorafenib combined with ICIs
Summary:
Hepatic artery infusion chemotherapy (HAIC) has shown promising outcomes in patients with
advanced hepatocellular carcinoma (HCC). Some patients can be converted to loco-regional
therapies after 4-6 cycles of HAIC treatment. But most of these patients still need to
concern the sequential treatment after standard HAIC treatment (4-6 cycles). Combination
of anti-angiogenic molecular targeted therapy and immune checkpoint inhibitor (ICI)
therapy has shown promising antitumor activity in HCC. Regorafenib is one of the standard
second-line systemic therapy for advanced HCC. In this study, we will evaluate the
efficacy and safety of sequential therapies of Regorafenib plus ICI in patients with
advanced HCC who have completed 4-6 cycles of HAIC.
Detailed description:
The standard procedure for HAIC is that femoral artery puncture and catheterization are
performed in every cycle of treatment, a micro-catheter is inserted and located in
feeding hepatic artery. The therapeutic scheme is modified FOLFOX6 regimens including
oxaliplatin, leucovorin and Fluorouracil. All chemo-drugs are given by HAI. A total of
4-6 cycles of HAIC are performed and the treated efficacy is evaluated. Patient who is
not suitable for loco-regional therapies after 4-6cycles of HAIC becomes to the candidate
of sequential therapies of regorafenib plus ICIs. The regorafenib 80 mg/day was uses in
sequential treatment. And ICIs were used intravenously at the standard dose. Patients
received sequential treatment will begin no earlier than 30 days following the last HAIC
procedure.
Criteria for eligibility:
Study pop:
Sequential and maintenance therapy of Regorafenib plus ICIs in andvanced HCC patients who
have completed standard HAIC.
Sampling method:
Non-Probability Sample
Criteria:
Inclusion Criteria:
Written informed consent must be obtained prior to any screening procedures.
- Cytohistological confirmation is required for diagnosis of HCC.
- Patients with advanced (unresectable and/or metastatic, stage C based on
Barcelona-Clinic Liver Cancer [BCLC] staging classification) hepatocellular
carcinoma who have completed 4-6 cycles HAIC. Treated efficacy evaluation has
confirmed that these patients are not suitable for loco-regional therapies or
surgical resection.
- At least one tumor lesion meeting measurable disease criteria as determined by
RECIST v1.1. Lesions previously treated with local therapy, such as radiation
therapy, hepatic arterial embolization, radiofrequency ablation, and percutaneous
interventional therapy should not be selected unless progression is noted at
baseline, in which case, these lesions would be considered as non-target lesions.
- Current cirrhotic status of Child-Pugh class A-B, with no encephalopathy. Ascites
controlled by diuretics is permitted in this study.
- Availability of a representative tumor tissue specimen (archival tumor tissue is
allowed) at pre-screening.
- Eastern Cooperative Oncology Group Scale for Assessment of Patient Performance
Status ≤ 2.
- Both men and women enrolled in this trial must use adequate barrier birth control
measures during the course of the trial and 4 weeks after the completion of trial.
- Adequate bone marrow, liver and renal function as assessed by central lab by means
of the following laboratory requirements from samples within 7 days prior to
procedure:
- Hemoglobin > 100g/L
- Absolute neutrophil count >3.0 ×109/L
- Neutrophil count > 1.5 ×109/L
- Platelet count ≥ 50.0 ×109/L
- Total bilirubin < 51 μmol/L
- Alanine transaminase (ALT) and aminotransferase (AST) < 5 x upper limit of normal
- Albumin > 28 g/L
- Prothrombin time (PT)-international normalized ratio (INR) < 2.3, or PT < 6 seconds
above control
- Serum creatinine < 110 μmol/L
- Willing and able to comply with scheduled visits, treatment plan and laboratory
tests.
Exclusion Criteria:
- A history of liver decompensation, such as refractory ascites, gastrointestinal
bleeding, or hepatic encephalopathy; Uncontrolled complications, including but not
limited to: Persistent or activity (except the HBV and HCV) infection, symptoms of
congestive heart failure and uncontrolled diabetes, uncontrolled hypertension,
unstable angina, uncontrolled arrhythmias, active ILD, severe chronic GI disease
accompanied by diarrhea, or compliance with requirements may limit the research,
resulted in significant increase risk of AE or influence Subjects provided
psychiatric/social problem status on their ability to provide written informed
consent. A history of active primary immunodeficiency or human immunodeficiency
virus; Active or previous records of autoimmune disease or inflammatory diseases,
including inflammatory bowel disease (e.g., colitis or Crohn's disease],
diverticulitis, except [diverticulosis], systemic lupus erythematosus (SLE),
sarcoidosis syndrome or Wegener syndrome (e.g., granulomatous vasculitis, gray's
disease, rheumatoid arthritis, the pituitary gland inflammation and uveitis]).
- Known to produce allergic or hypersensitive reactions to any study drug or any
excipient thereof;
- Significant clinical gastrointestinal bleeding or a potential risk of bleeding was
identified by the investigator during the 30 days prior to study entry.
- Tumors of the central nervous system, including metastatic brain tumors;
- Pregnant women or breast-feeding patients;
- Complicated with other malignant tumors:
- Malignant tumors that have been treated for therapeutic purposes, have no known
active disease for 5 years prior to the first administration of the study drug, and
have a low potential risk of recurrence.
- Fully treated non-melanoma skin cancer or malignant freckle moles with no evidence
of disease.
- Fully treated carcinoma in situ without evidence of disease.
- Prior to the initial dosing of the study drug, they had received anti-PD-1,
anti-PD-L1, or anti-CTLA-4 therapy.
- Has received anti-tumor system therapy for HCC. Non-anti-tumor purpose combined
hormone therapy (e.g., hormone replacement therapy) is excluded.
- Is currently using, or has used an immunosuppressive drug within 14 days prior to
the first dose of the investigational drug. This standard has the following
exceptions:
- intranasal, inhaled, topical or topical steroids. (e.g., intraarticular)
- Systemic corticosteroid therapy not exceeding 10 mg/ day of prednisone or its
physiological equivalent as a prophylactic use of steroids for hypersensitivity.
(e.g., CT scan pretherapy medication)
- Steroids as a prophylactic for allergic reactions.
- A live attenuated vaccine was administered within 30 days prior to the first
administration of the study drug. Note: If enrolled, patients shall not receive live
attenuated vaccine within 30 days of receiving study drug therapy and after the last
administration of study drug.
- Uncontrolled hypertension: systolic pressure ≥ 160 mmHg or diastolic pressure ≥ 100
mmHg despite anti-hypertension medications ≤ 28 days before randomization or first
dose of drug.
- Pregnant or lactating women, or fertile men or women who do not want to use
high-efficiency contraceptives, 6 months after the last dosing of study treatment,
from screening to study treatment. Based on the patient's preferred and customary
lifestyle, abstinence during treatment and washout is an acceptable contraceptive
method.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Department of Minimally Invasive and Interventional Radiology, Liver Cancer Study and Service Group, Sun Yat-sen University Cancer Center,
Address:
City:
Guangzhou
Zip:
500060
Country:
China
Status:
Recruiting
Contact:
Last name:
Ming Zhao, MD
Phone:
86-20-87343272
Email:
zhaoming@sysucc.org.cn
Facility:
Name:
Sun Yat-sen University Cancer Center
Address:
City:
Guanzhou
Zip:
510060
Country:
China
Status:
Recruiting
Contact:
Last name:
Ming Zhao, PHD
Phone:
+86-20-87343272
Email:
zhaoming@sysucc.org.cn
Start date:
October 16, 2022
Completion date:
January 1, 2026
Lead sponsor:
Agency:
Sun Yat-sen University
Agency class:
Other
Source:
Sun Yat-sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05573282
