TACE Combined With Sintilimab and Bevacizumab for Unresectable HCC

Second Affiliated Hospital of Guangzhou Medical University

Status and phase

Unknown

Phase 1

Conditions

Hepatocellular Carcinoma Non-resectable

Treatments

Drug: TACE combined with sintilimab and bevacizumab

Study type

Interventional

Funder types

Other

Identifiers

NCT04592029

MIIR-02

Details and patient eligibility

About

This study is to evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) combined with sintilimab and bevacizumab in patients with unresectable intermediate or advanced hepatocellular carcinoma (HCC).

Full description

This is a Phase Ib study to evaluate the safety and efficacy of TACE combined with sintilimab and bevacizumab in patients with unresectable intermediate or advanced HCC.

36-39 subjects with unresectable intermediate or advanced HCC will be enrolled in the study.

This study includes dose escalation and dose expansion stage. 6-9 subjects will be enrolled in dose escalation stage for the safety evaluation. Then, sintilimab 200mg/kg IV. every three weeks (q3w) + the select specific dose of bevacizumab 7.5mg/kg (group 1) or 15mg/kg (group2) IV q3w, expand to 36 patients (18 patients each group) for the further safety and efficacy study.

Sintilimab and bevacizumab will be started at 3-7 days after the first TACE. TACE will be repeated if clinically indicated based on the evaluation of follow-up laboratory and imaging examination. And the study treatment of sintilimab and bevacizumab will last up to 24 months, or until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first.

Enrollment

36 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Intermediate or advanced (Barcelona Clinic Liver Cancer stage B or C) HCC with diagnosis confirmed by histology/cytology or clinically
Disease not amenable to curative therapies but amenable to TACE
At least one measurable untreated lesion
No prior systemic therapy for HCC
Child-Pugh score class 5-7
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment
Adequate organ and hematologic function
Life expectancy of at least 3 months
For women of childbearing potential and for men: agreement to remain abstinent

Exclusion criteria

Diagnosis of fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
Diffuse HCC
Portal vein tumor thrombus (PVTT) involves the main trunk and contralateral branch or upper mesenteric vein
Inferior vena cava tumor thrombus
Metastatic disease that involves major airways or blood vessels
Symptomatic, untreated or progressing central nervous system metastasis
Uncontrolled tumor-related pain
Patients who received prior systemic therapy, immunotherapy, TACE, transcatheter arterial radioembolization (TARE), transcatheter arterial embolization (TAE), hepatic arterial infusion chemotherapy (HAIC) or radiation therapy for HCC
Treatment with systemic immunostimulatory agents
Use of herbal therapies or traditional Chinese medicines with anti-cancer activity within 2 weeks
History of malignancy other than HCC within 5 years prior to screening, except for malignancies with a negligible risk of metastasis or death
Uncontrolled ascites, hydrothorax or pericardial effusion
Prior esophageal and/or gastric varices bleeding within 6 months prior to initiation of study treatment
Prior life-threatening blood loss or grade 3/4 gastrointestinal bleeding requiring blood infusion, endoscopic or surgical intervention within 3 months
Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high-risk for bleeding
History of gastrointestinal (GI) perforation and/or fistula in the past 6 months
history of GI obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection, complicated by chronic diarrhea), Crohn's disease, ulcerative colitis or long-term chronic diarrhea
History of hepatic encephalopathy
History of organ and stem cell transplantation
Long-term daily treatment with a non-steroidal anti-inflammatory drug (NSAID)
Use of immunosuppressive drugs in the past 4 weeks, excluding the routes of topical glucocorticoids or physiological doses of systemic glucocorticoids (ie no more than 10 mg/day of prednisone or equivalent). Temporary use of glucocorticoids for dyspnea symptoms such as asthma and chronic obstructive pulmonary disease is allowed
History of idiopathic pulmonary fibrosis, interstitial pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
Active tuberculosis
Active severe infection; use of antibiotics within 2 weeks prior to injection of sintilimab
Autoimmune disease or immune deficiency
Inadequately controlled hypertension; history of hypertensive crisis or hypertensive encephalopathy
Bleeding diathesis or significant coagulopathy
Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
underwent major surgery (craniotomy, thoracotomy or open surgery) within 4 weeks; non-recovery from side effects of these procedure
History of venous thromboembolism in the past 6 months, but implantable IV ports or catheter-derived thrombosis, superficial venous thrombosis, or thrombosis after conventional anticoagulant therapy are excluded
Current or recent use of aspirin or treatment with dipyramidole, ticlopidine, clopidogrel, or cilostazol
uncontrolled metabolic disorder, non-malignant organ or systemic disease or secondary carcinomatous reaction, with high medical risk and/or uncertainty of life expectancy evaluation
Other acute or chronic diseases, mental illness, or abnormal laboratory test results that may lead to the following outcomes: increase the risk of participating in study or study drug administration, or interfere with the interpretation of the study results and considered by investigator as "NOT" eligible to participate in this study
Female patients who are pregnancy or breastfeeding