AzTrials
AzTrials

Hepatocellular CarcinomaPhase 2NCT04653389

Perioperative Therapy for Hepatocellular Carcinoma

A Phase 2 study testing Sintilimab Injection, TACE and Radiotherapy in people with Hepatocellular Carcinoma, run by Zhejiang University at 1 site in China.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Hepatocellular Carcinoma
What is being tested?
Sintilimab Injection, TACE and Radiotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteChina
Study dates
26 Dec 2020to 1 Dec 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)；
Show all 15Show fewer
  • 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.

Who cannot join

  • 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).
Show all 17Show fewer
  • 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.
  • Patients with a history of hepatic encephalopathy or a history of liver transplantation or patients preparing for liver transplantation;
  • Pregnant or lactating women; Known to be allergic to any antibody-targeted drug or small-molecular-targeted drug ingredient; Or have a history of severe allergic reactions to other monoclonal antibodies.

Trial locations and contacts

1 site in 1 country.

China1 site

  • the First Affiliated Hospital, School of Medicine, Zhejiang University

    Hangzhou, Zhejiang, 310003

Other trials in China

About this study

Official title: Perioperative Multidisciplinary Therapy for Technically Resectable Hepatocellular Carcinoma With Vein Thrombosis: An Exploratory Clinical Trail

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.

Read the detailed description

Hepatocellular carcinoma (HCC) has an insidious onset, high degree of invasion, and rapid disease progression. Tumor cells can easily invade the intrahepatic vasculature, especially the portal vein or hepatic venous system, and form portal vein tumor thrombus (PVTT) or hepatic vein tumor thrombus (HVTT).PVTT/HVTT is one of the main adverse factors for the long-term survival of HCC. The location and scope of its occurrence are closely related to the prognosis, and it is also a main hindrance to the improvement of the overall curative effect of HCC in recent years.

As the treatment of HCC converts to multi-disciplinary therapy, the neoadjuvant therapy will be commonly used in the treatment of HCC with PVTT.Early clinical data already support a safe combination of immune checkpoint inhibition with TACE. Moreover，The preliminary results of our previous trial (CISLD-5) showed that TACE combined with anti-programmed-death-1 antibody in patients with BCLC stage A/B HCC beyond Milan criteria has a significant effect.In addition, radiation therapy (RT) can irradiate both the tumor thrombus and the primary tumor .In numbers of retrospective studies, preoperative radiotherapy can achieve radical resection in some patients.

This study is to analyze the safety and efficacy of preoperative TACE and anti-PD-1 Injection combined with or without preoperative radiotherapy of vein tumor thrombus and postoperative anti-PD-1 injection in the treatment of technically resectable hepatocellular carcinoma patients with vein thrombosis.

Being tested
Sintilimab Injection, TACE, Radiotherapy
Keywords
Hepatocellular carcinoma, Vein tumor thrombus, Transarterial chemoembolization, Immunotherapy, Radiotherapy, Multi-disciplinary treatment
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sintilimab InjectionDrug

    Also called Immunotherapy, Anti-PD-1 therapy

    Sintilimab Injection is used as neoadjuvant therapy and adjuvant therapy.

  • TACEDrug

    Also called Transarterial Chemoembolization

    The first TACE and Sintilimab Injection will be initiated simultaneously.

  • RadiotherapyRadiation

    Also called hypofractionated radiation therapy

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

Study groups in NCT04653389
Study groupRoleWhat they receive
Preoperative TACE+Sintilimab+/-Radiotherapy of vein tumor thrombus+postoperative SintilimabExperimentalThe 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.
Receives: Drug: Sintilimab Injection; Drug: TACE; Radiation: Radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Observation period 48 months

Secondary outcomes (6)

  1. Duration of Response（DOR）

    Time between the date of first radiographic documented objective response according to mRECIST for HCC and the date of the radiographic disease progression.

    Measured: 48 months

  2. Major Pathological response rate（MPR）

    Number of participants experiencing the percentage of the non-viable cancer cells (necrotized or fibrotized) out of the surface expression of the total tumor area is <10%

    Measured: 48 months

  3. Disease Free Survival（DFS）

    The time from the patient received surgery to the disease progressed, or died from any cause.

    Measured: 48 months

  4. Overall survival (OS)

    Time from first treatment until death

    Measured: 48 months

  5. Adverse events

    Safety evaluation was done continuously during treatment by using CTCAE 5.0

    Measured: 48 months

  6. Tumor biomarker

    Including but not limited to AFP,PD-L1,TMB,MSI,HLA,etc.

    Measured: 48 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Dec 2020
  2. Study start26 Dec 2020
  3. Primary completion1 Oct 2021
  4. Study completion1 Dec 2021

Why it stopped: The treatment efficacy was not satisfactory.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Single Group Assignment A Phase II Single-arm, Open-label Study
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04653389
Sponsor's protocol ID
CISLD-10
Status last verified
Feb 2021
First submitted
28 Nov 2020
Last updated
11 Jan 2022
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sintilimab Injection, TACE and Radiotherapy in people with Hepatocellular Carcinoma, run by Zhejiang University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 11 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The treatment efficacy was not satisfactory.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event Free Survival（EFS） (time frame: Observation period 48 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04653389.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in