Perioperative Therapy for Hepatocellular Carcinoma

NCT04653389 | Terminated Phase 2

• 1 other identifier: CISLD-10
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to observe and evaluate the efficacy and safety of the perioperative multidisciplinary therapy that combines the preoperative transarterial chemoembolization(TACE) and the anti-programmed-death-1 antibody (anti-PD-1) Sintilimab Injection with or without radiotherapy of vein tumor thrombus followed by postoperative anti-PD-1 injection in the treatment of technically resectable hepatocellular carcinoma patients with vein thrombosis.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular carcinoma; Vein tumor thrombus; Transarterial chemoembolization; Immunotherapy; Radiotherapy; Multi-disciplinary treatment

Outcome Measures

Primary Outcomes (1)

• Event Free Survival（EFS）

  The time from the patient received treatment to the disease progressed, or the disease recurred after surgical resection without preoperative disease progression, or died from any cause.

  Observation period 48 months

Secondary Outcomes (6)

• Duration of Response（DOR）

  48 months

• Major Pathological response rate（MPR）

  48 months

• Disease Free Survival（DFS）

  48 months

• Overall survival (OS)

  48 months

• Adverse events

  48 months

Study Arms (1)

Preoperative TACE+Sintilimab+/-Radiotherapy of vein tumor thrombus+postoperative Sintilimab

EXPERIMENTAL

The first TACE and immunotherapy will be performed at the same time on the first day of treatment. Anti-PD-1 Injection will be administered every three weeks ,until the disease progresses according to mRECIST criteria or intolerable toxicity or the patients' request, or surgery.Hypofractionated radiation therapy will be adopted for Type Vp2, Vp3 PVTT or Type Vv2 HVTT about 2 weeks after the first TACE.If the imaging examination 4 weeks after the surgery confirm that there is no recurrence and no contraindications to receive immunotherapy, anti-PD-1 antibody adjuvant therapy can be started.Every 21 days is a course of treatment, and the longest medication duration lasts for 6 months.

Drug: Sintilimab Injection; Drug: TACE; Radiation: Radiotherapy

Interventions

Sintilimab Injection DRUG

Sintilimab Injection is used as neoadjuvant therapy and adjuvant therapy.

Also known as: Immunotherapy, Anti-PD-1 therapy

Preoperative TACE+Sintilimab+/-Radiotherapy of vein tumor thrombus+postoperative Sintilimab

TACE DRUG

The first TACE and Sintilimab Injection will be initiated simultaneously.

Also known as: Transarterial Chemoembolization

Preoperative TACE+Sintilimab+/-Radiotherapy of vein tumor thrombus+postoperative Sintilimab

Radiotherapy RADIATION

Use Cone Beam computor tomography(CBCT) locates the lession before the therapy.

Also known as: hypofractionated radiation therapy

Preoperative TACE+Sintilimab+/-Radiotherapy of vein tumor thrombus+postoperative Sintilimab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly histologically confirmed diagnosis of HCC or strictly consistent with the clinical diagnostic criteria for HCC according to AASLD guideline；
• At least one measurable site of disease as defined by modified RECIST (mRECIST) criteria with spiral CT scan or MRI and has not received local treatment；
• Technically resectable hepatocellular carcinoma with ipsilateral vein tumor thrombosis, including Vp1, Vp2, Vp3 portal vein tumor thrombus (PVTT) (Japan JSH classification) and/or Vv1, Vv2 hepatic vein tumor thrombus (HVTT) (Japan JSH) Type), but not accompanied with extrahepatic organ metastasis, or main portal vein,contralateral portal vein, superior mesenteric vein, vena cava tumor thrombus.Bile duct tumor thrombus can be allowed;
• tumor burden below 50% of standard liver volume；
• ECOG PS score: 0\~1 points
• Child-Pugh A or B (\<=7)；
• Life expectancy of at least 3 months;
• Subjects with chronic HBV infection must be on antiviral therapy per regional standard of care guidelines prior to initiation of study therapy；
• Adequate blood count, liver-enzymes, and renal function: laboratory test values meet the following requirements within 7 days prior to enrollment (no blood components, cell growth factors, albumin and other corrective therapy drugs are allowed within 14 days prior to laboratory test):
• absolute neutrophil count, ANC≥1.5×10\^9/L, platelet, PLT≥80×10\^9/L, hemoglobin, HGB≥8.5 g/dL;
• total bilirubin, TBIL≤1.5×ULN, alanine aminotransferase, ALT and aspartate transferase, AST≤5×ULN, serum Alb≥28 g/L；
• creatinine, Cr ≤ 1.5×ULN or clearance of creatinine, CCr≥ 50mL/min, Urine protein\<2+;
• INR≤ 2 and APTT≤ 1.5×ULN.
• Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial；
• Patients agreed to join the clinical trial and signed informed consent and are willing and able to comply with the protocol for the duration of the study including undergoing treatment, adherence to contraceptive measures, scheduled visits and examinations including follow up.

You may not qualify if:

• Have received local or systemic treatments in the past, including but not limited to TACE, immunotherapy, targeted therapy, radiotherapy, radiofrequency therapy, etc.;
• Diffuse HCC or accompanied by distant metastasis;
• fibrolamellar carcinoma of liver,cholangiocarcinoma and mixed liver cancer;
• Insufficient residual liver volume(According to imaging calculations, if there is no background of cirrhosis, the remaining liver volume is less than 35% of the standard liver volume; if there is a background of cirrhosis, the remaining liver volume is less than 40% of the standard liver volume)
• Active tuberculosis (TB), who are receiving anti-TB treatment or who received anti-TB treatment within 1 year prior to the first study；Patients with previous or current objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, and severe impairment of lung function.
• Patients With II-IV myocardial ischemia and myocardial infarction, poor control of cardiac arrhythmias; Patients with hypertension who cannot be reduced to the normal range after antihypertensive medication (systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg).
• A history of gastrointestinal perforations and/or fistulas, intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), inflammatory bowel disease or extensive bowel resection (partial colectomy or extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea within 6 months; Patients with a history of gastrointestinal bleeding or a clear gastrointestinal bleeding tendency in the past 6 months, such as esophageal varices with bleeding risk, local active ulcer lesions, and fecal occult blood (++).
• Severe bleeding tendency or coagulation dysfunction, or receiving thrombolytic treatment; Any life-threatening bleeding event that has occurred within the previous 6 months, including the need for blood transfusion, surgery or topical treatment, and continued medication.
• Autoimmune disease requiring systematic treatment or a history of the disease within 2 years. (such as vitiligo, psoriasis, hair loss or graves' disease).
• Patients with central nervous system diseases (such as primary brain tumors, stroke, epilepsy, etc.) or central nervous system metastasis or known brain metastasis.
• Acute or chronic active hepatitis B or C infection; Human immunodeficiency virus (HIV) infection (HIV 1/2 antibody positive); . A severe infection that is active or clinically poorly controlled. Severe infections, including but not limited to hospitalization for infection, bacteremia, or complications of severe pneumonia, occurred 1 month before the first study.
• Contains fibroblastic layer hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, bile duct carcinoma and other components; Other malignancies were diagnosed within 5 years prior to the first administration, excluding radical basal cell carcinoma of the skin, skin squamous cell carcinoma and/or radical resection of carcinoma in situ. If other malignancies or liver cancer are diagnosed more than 5 years before administration, a pathological or cytological diagnosis of the relapsed and metastatic lesions is required.
• Previous major surgery (craniotomy, thoracotomy, or laparotomy) within 1 month or unhealed wounds, ulcers, or fractures; Severe arteriovenous fistula; Uncontrolled metabolic disorders or other non-malignant organ or systemic disease or cancer secondary reactions and may result in higher medical risk and/or uncertainty in survival evaluation.
• Treated with immunosuppressive drugs, live attenuated vaccine, systemic immunostimulant therapy, or any anti-PD-1, anti-PD-L1/L2 antibody or other immunotherapy and experimental drugs within 4 weeks or planned during the study period.
• Other acute or chronic conditions, psychiatric disorders, or laboratory abnormalities that may increase the risk of study participation or administration of the study drug, or interfere with the interpretation of the study results, and classify patients as ineligible to participate in the study at the discretion of the investigator.

Sponsors & Collaborators

• Zhejiang University: lead

Study Sites (1)

the First Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310003, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

sintilimab; Immunotherapy; Radiotherapy

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)

Immunomodulation; Biological Therapy; Therapeutics

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: Professor

Model Details: Single Group Assignment A Phase II Single-arm, Open-label Study

Study Record Dates

• First Submitted: November 28, 2020
• First Posted: December 4, 2020
• Study Start: December 26, 2020
• Primary Completion: October 1, 2021
• Study Completion: December 1, 2021
• Last Updated: January 11, 2022

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)