Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Liver Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Doxorubicin

Liposomal doxorubicin

Chlorotrianisene

Liver Extracts

Ethiodized Oil

Before TACE, hepatic arteriography was performed to evaluate the vascular anatomy and tumour vascularity. During TACE, a vascular catheter was selectively inserted into the tumour-feeding artery with an injection containing a mixture of doxorubicin (10-50 mg) and lipiodol (2-20 mL), followed by embolisation using gelatin sponge particles. TACE was repeated when residual viable tumours were confirmed or new lesions developed in patients with adequate liver function. Laboratory assessments were performed every four to six weeks. Radiological evaluation using contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) was recommended during weeks 4 and 8 after treatment and every 8 weeks thereafter. However, in clinical practice, the intensity of follow-up depends on an individual's baseline characteristics and response to the last treatment.

transarterial chemoembolisation

zhao s jie

Hepatic dysfunction limits the therapeutic options for hepatocellular carcinoma (HCC), which is closely associated with patient prognosis. Established practice guidelines for patients with HCC and impaired liver function are lacking. The treatment allocation in these populations is heterogeneous and remains controversial. This study compared the survival benefits of liver resection (LR) and transarterial chemoembolisation (TACE) in patients with HCC and impaired liver function.

Liver Resection for Patients With Hepatocellular Carcinoma and Impaired Liver Function

Liver Resection for Patients With Hepatocellular Carcinoma and Impaired Liver Function: A Chinese Multicenter Observational Study

Tang-Du Hospital

Heart and Blood Diseases

Hypertension

Hypertension, Portal

Bevacizumab

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

bevacizumab 5 mg/kg i.v. every 14 days for 52 weeks

bevacizumab

Markus Peck-Radosavljevic, M.D.

Patients with liver cirrhosis and hepatocellular carcinoma will undergo transarterial chemoembolisation (TACE) as clinically indicated and will be randomized to receive bevacizumab or placebo every 2 weeks up to 1 year. Tumor response will be assessed using MR of the liver and PET-scanning.

It will be tested whether the addition of bevacizumab as angiogenic inhibitor will slow down tumor progression, reduce the need for re-embolisation and will improve patient survival.

TACE is an established therapy for patients with advanced stage HCC not amenable to liver transplantation or resection and has been shown to significantly improve survival in these patients compared to no treatment (8). TACE takes advantage of the predominantly arterial blood supply of malignant liver tumors contrary to the surrounding normal liver tissue, which receives more blood supply through the portal venous system.

TACE leads to predictable tumor necrosis until new blood vessels grow into the tumor margins to support tumor growth. Quite often after cutting off the blood supply through the hepatic artery, the tumor induces active angiogenesis to promote collateral blood vessel growth from liver capsule arteries or collaterals from the gastroduodenal artery. VEGF seems to be an important player in inducing this angiogenetic activity and tumor control and survival of patients after TACE have been linked to serum VEGF-levels with higher levels showing reduced survival.

Inhibition of these neoangiogenetic activity could lead to significantly improved in tumor control and survival in patients with advanced stage HCC.

2. STUDY OBJECTIVE

* to assess the effectiveness of bevacizumab in combination with TACE as measured by patients without tumor progression on MRT after 3 cycles of TACE as well as the number of TACE cycles applied for recurrent tumor after a maximum of one year treatment with bevacizumab
* to assess collateral tumor vessel growth on MRT / CT

Transarterial Chemoembolisation Plus Bevacizumab for Treatment of Hepatocellular Carcinoma

AVATACE-1: Bevacizumab (Avastin®) as Inhibitor of Collateral Tumor Vessel Growth During Transarterial Chemoembolisation (TACE) for Hepatocellular Carcinoma (HCC) a Pilot Trial

Medical University of Vienna

Markus Peck-Radosavljevic, M. D.

Lenvatinib

Protein Kinase Inhibitors

Enzyme Inhibitors

Patients in Lenvatinib + TACE group will take oral lenvatinib within 3 days of randomization and receive TACE 1 day after oral administration of lenvatinib.

TACE will be performed one day after oral administration of lenvatinib. TACE with either cTACE or DEB-TACE can be used, depending on the condition of each center.

TACE

Lenvatinib will be taken within 3 days of randomization (dose: 8 mg qd for patients \<60kg, and 12 mg qd for patients \>60kg)

Ming Kuang, PhD

Ming Kuang, Ph.D.

This trial is is an open label, multicenter, randomized controlled phase 3 clinical trial. The purpose is to compare the efficacy and safety of lenvatinib plus TACE with lenvatinib alone for advanced HCC patients.

TACE With Lenvatinib Versus Lenvatinib Alone in in First-line Treatment of Advanced HCC

Transarterial Chemoembolization With Lenvatinib Versus Lenvatinib Alone in First-line Treatment of Advanced Hepatocellular Carcinoma: a Phase III, Multicenter, Randomized Controlled Trial

Defined as the time from randomization to death for any cause.

Defined as the time from randomization to disease progression.

Sun Yat-sen University

Clinical Professor

Coagulants

Cisplatin

Gelatin Sponge, Absorbable

Transarterial chemoembolisation will be performed 4 to 6 weeks after hepatectomy

Cisplatin-lipiodol mixture was infused through catheter placed at hepatic artery followed by gelfoam embolisation. This is performed 4 to 6 weeks after surgery

Transarterial chemoembolisation using cisplatin-lipiodol mixture

Yue Sun Cheung, MBChB

We hypothesise that the use of transarterial chemoembolisation (TACE) after liver resection in patients with hepatocellular carcinoma can eradicate residual cancer cells in the liver and thus improve survival. The aim of this study is to compare the survival of patients undergoing liver resection plus post-operative TACE versus liver resection alone.

Liver resection is the mainstay of curative treatment for hepatocellular carcinoma (HCC). However, recurrence is common after surgery and most occurs in the liver. Transarterial chemoembolisation (TACE) is an effective palliative treatment for HCC. It involves the infusion of chemotherapeutic agent admixed with iodised oil followed by embolisation of the hepatic arterial flow using small particles. This procedures allows application of smaller dose of chemotherapy concentrated to the liver and thus is well tolerated with minimal side effects. We conduct a randomised controlled trial evaluating the efficacy of using TACE after hepatectomy in HCC patients.

RCT on Adjuvant TACE After Hepatectomy for HCC

Randomised Controlled Trial on Adjuvant Transarterial Chemoembolisation After Curative Hepatectomy for Hepatocellular Carcinoma

The 1-year recurrence rate after hepatectomy in both arms of study were compared

The quality of life assessment was measured by Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire (Chinese version 3)

Chinese University of Hong Kong

Dr Cheung Yue Sun

Vascular Diseases

During transarterial chemoembolisation（TACE）, a vascular catheter was selectively inserted into the tumour-feeding artery with an injection containing a mixture of doxorubicin (10-50 mg) and lipiodol (2-20 mL), followed by embolisation using gelatin sponge particles. TACE was repeated when residual viable tumours were confirmed or new lesions developed in patients with adequate liver function

Clinically significant portal hypertension limits the therapeutic options for hepatocellular carcinoma (HCC), which is closely associated with patient prognosis. HCC patients with CPSH are heterogeneous and treatment allocation remains controversial. The aim of this study was to compare the survival benefits of liver resection (LR) and transarterial chemoembolisation (TACE) in these populations.

Liver Resection for Patients With Hepatocellular Carcinoma and Clinically Significant Portal Hypertension

Liver Resection for Patients With Hepatocellular Carcinoma and Clinically Significant Portal Hypertension: A Chinese Multicentre Retrospective Cohort Study

All patients treatment with Donafenib plus Sintilimab in combination with TACE

Donafenib plus Sintilimab in combination with transarterial chemoembolisation (TACE)

Donafenib plus Sintilimab in combination with transarterial chemoembolisation

Xiaoyun Hu

Jinzhang Chen

To evaluate the efficacy and safety of Donafenib plus Sintilimab in combination with transarterial chemoembolisation (TACE) in patients with unresectable hepatocellular carcinoma(HCC).

Transarterial chemoembolisation (TACE) was effective and safe for hepatocellular carcinoma. Donafenib was better than sorafenib in overall survival in untreated advanced hepatocellular carcinoma, and programmed cell death protein-1 (PD-1) antibody was effective and tolerable in patients with advanced hepatocellular carcinoma. No study has evaluated TACE plus donafenib and sintilimab. Thus, the investigators carried out this prospective, single-arm study to find out it.

Donafenib Plus Sintilimab in Combination With TACE in Patients With Unresectable Hepatocellular Carcinoma

A Prospective, Single-arm, Phase II Clinical Study of the Efficacy and Safety of Donafenib Plus Sintilimab Combined With Transarterial Chemoembolization (TACE) in Patients With BCLC Stage B/C Hepatocellular Carcinoma

ORR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) at the time of data cutoff as assessed by RECIST 1.1

DCR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) or stable disease (SD) at the time of data cutoff as assessed by RECIST 1.1

DOR is defined as the time from the first documentation of CR or PR to the date of first documentation of disease progression or death (whichever occurs first) as assessed by RECIST 1.1

The progression free survival time defined as the time from the first study dose date to the date of first documentation of disease progression as assessed by RECIST 1.1

Overall survival rate is measured from the start date of the Treatment Phase (date of first study dose) until date of death from any cause. Participants who are lost to follow-up and the participants who are alive at the date of data cutoff will be censored at the date the participant was last known alive or the cut-off date, whichever comes early.

Nanfang Hospital, Southern Medical University

Anti-Infective Agents

Central Nervous System Depressants

Thalidomide

Anesthetics

Capecitabine

* Under local anesthesia, the Femoral artery would be punctured
* A catheter would be introduced and a flush aortogram, superior mesenteric arterioportography and the celiac artery run would be undertaken to define the size and location of the tumors, feeding vessels and to assess the portal vein patency
* Superselective catheterization of the hepatic artery feeding the tumor would be done
* By placing the catheter tip beyond the gastroduodenal artery, the chemotherapeutic drugs would be administered.
* Stable drug mixture would be prepared by using Doxorubicin 50mg, Cisplatin 100mg in combination with 10-15ml of ionic contrast media and 10-20ml of lipiodol by continuously agitating the mixture.
* The drug mixture would then be injected through the indwelling arterial catheter by continuously flushing alternately, repeatedly and rapidly between two-luer locks syringes connected across a three way.
* Gelfoam particles would be injected following this for embolization

Subrat K Acharya, D.M

Shashi B Paul, Ph.D

Shivanand Gamanagatti, MD

Kaushal Madan, DM

Sreenivasa B Chalamalasetty, DM

Sreenivas Vishnubhatla, Ph.D

Subrat K Acharya, DM

Background Hepatocellular carcinoma, a malignant tumor of liver is one of the most common cancers worldwide. All India Institute Of Medical Sciences (AIIMS) being a tertiary care hospital receives about two to three cases of Hepatocellular carcinoma (HCC) each day in our Gastroenterology out patient department. Most of these patients present late when the disease is already advanced and no curative therapies can be offered. At this stage, palliative therapy forms the mainstay of treatment. This includes TACE or Oral chemotherapy. Whether oral chemotherapy administered along with TACE potentiates the effect and further prolongs survival, needs to be ascertained. No studies of this kind are available.

This prospective study is therefore designed to address this issue.

1. Subjects Consecutive patients of unresectable HCC diagnosed from January 2006 at the liver clinic, AIIMS will be included in the study if they fulfill the following criteria-

   Inclusion criteria · Patients above 12 years of age with performance status (PST)score of 0-2

   · Unresectable HCC with underlying Child's A/B cirrhosis

   · Normal Main portal vein and its branches
   * Normal Inferior vena cava
   * No history of drug allergy
   * Informed written consent of patient.
   * Less than 50% involvement of liver by HCC

   Exclusión criteria

   · Unresectable HCC with underlying Child's C cirrhosis

   · Performance status 3-5

   · Extrahepatic disease

   · Vascular involvement
   * Co-morbid illness like coronary artery disease, congestive heart failure, chronic renal failure etc
   * Previous history of encephalopathy/ upper gastrointestinal bleed in the last six months
   * HCC in a female of child bearing age
2. Diagnostic criteria

   * Cirrhosis of liver- Diagnosis will be founded on the basis of clinical, biochemical and endoscopy findings.
   * Hepatocellular carcinoma- when any one of the following is present



1. Any two imaging modalities(Ultrasound (US), dual phase CT (DPCT)/ contrast enhanced MRI) showing arterialization of the hepatic mass
2. AFP more than 400ng/ml along with arterialisation on one imaging modality (DPCT/ contrast enhanced MRI)
3. FNAC

3. Randomization

· Patients will be randomized after the confirmation of diagnosis and obtaining written consent

· Sequences will be generated by the Statistician

· Stratified randomization will be done. Two strata of child's A and B will be made

· Randomization will be done by drawing consecutively numbered opaque sealed envelopes

· Randomization into A (TACE) and B (TACE +oral chemotherapy) will be done.

4. Definitions

1. Unresectable HCC-

   · Liver mass larger than 5cm in diameter (single/ multiple), involving less than 50% of the liver.

   · Multiple masses more than three in number and more than 3cm in diameter.
2. Tumor response

   This will be based on Dual phase CT findings

   · Complete response (CR)- Tumor fully covered with lipiodol showing no viable tissue
   * Partial response (PR)- Tumor partially covered (\>75%) by lipiodol
   * Mild response (MR)- About 50 to 75% coverage of the tumor by lipiodol
   * No response (NR) - About 25 to 50% coverage of the tumor by lipiodol
   * Fresh lesions (FL)- Appearance of new mass lesions in the liver with or without recurrence at the site of previous mass
3. Patient tolerance- Grade 1: no side effects Grade 2: moderate side effects Grade 3: severe side effects Grade 4: life threatening side effects
4. Performance status (PST score)

   PST score of 0-5 would be assessed on the following basis 0- No cancer related symptoms. Normal life style 1- Minor symptoms related to cancer. Capable of non-strenuous activity. Fully ambulatory 2- Ambulatory and capable of all self care but unable to carry out any work activities Confined to bed less than 50% of waking hours 3- Capable of only limited self care. Confined to bed more than 50% of waking hours.

   4- Completely disabled. Cannot carry on any self care. Totally confined to bed. 5- Death

   5. Sample Size Systematic review of RCTs for TACE show a 2 year survival of 37%. Expecting that addition of oral drugs would increase survival to 37 to 60%, for a power of 80% and error of 5%, a sample size of 73 patients in each arm would be required (Total 146 patients).

   6. Procedure of TACE

   · Patient would be admitted a day prior to the procedure

   · Patient would be made to fast overnight with intravenous fluid infusion started for maintaining hydration

   · Pre-procedure analgesic (3rd generation antibiotic) would be started at a dose of 2gm intravenously, 12 hourly, at least 12 hour before the procedure and continued 5 days post procedure

   · Under local anesthesia, the Femoral artery would be punctured at the upper thigh with a Medicut 18 gauge

   · A catheter would be introduced through this route with the help of a guide wire and a flush aortogram, superior mesenteric arterioportography and the celiac artery run would be undertaken to define the size and location of the tumors, feeding vessels and to assess the portal vein patency

   · Superselective catheterization of the hepatic artery feeding the tumor would be done

   · By placing the catheter tip beyond the gastroduodenal artery, the chemotherapeutic drugs would be administered.

   · Stable drug mixture would be prepared by using Doxorubicin 50mg, Cisplatin 100mg in combination with 10-15ml of ionic contrast media and 10-20ml of lipiodol by continuously agitating the mixture.

   · Hydrocortisone 100mg and augmenting dose of analgesic and sedative would be injected prior to the administration of the drug.

   · The drug mixture would then be injected through the indwelling arterial catheter by continuously flushing alternately, repeatedly and rapidly between two lever lock syringes connected across a three way.

   · Gelfoam particles would be injected following this for embolization

   · Post procedure, devascularization would be confirmed by additional angiography of the hepatic artery.

   · Procedure would last approx 45mts-1 hour.

   · Tight compression would be given at the punctured site and patient would be shifted to the ward once complete hemostasis is achieved.

   7. Follow up post TACE Clinical follow up
   * All patients would be followed up in the Liver clinic monthly unless their clinical condition warrants earlier follow up
   * Liver function tests/ complete blood count would also be done at each visit and AFP (if elevated earlier) every six months
   * Patient tolerance, child's status would be estimated. Imaging follow up
   * At one month, a dual phase CT would be done to ascertain the response to therapy and the need to repeat the procedure. Subsequently, the DPCT would be done at 3 and 6 monthly intervals.
   * Once the tumor shows complete coverage, randomization into the two treatment groups would be done

     9. Repeat TACE on follow up This would be done if any of the following is noted
   * DPCT shows viable tumor
   * Fresh lesions appear
   * Elevated serum AFP occurs with or without appearance of viable mass on DPCT

     10. Oral chemotherapy Drugs used would be Thalidomide and Capecitabine in the following dosage schedule-

   Thalidomide---100mg once a day (OD) for 7 days, Increased to 200mg OD for 7 days, further increased to 300mgOD for 7 days till a maximum of 600mg once a day is reached

   Capecitabine---- 500mg OD for 7 days, then 1000mg OD for next 7 days, increased to a maximum dose of 1500mg OD.

   Total leucocyte count \& Platelet count would be monitored every 15 days

   11. Duration of follow up- Two years after achieving total coverage of the mass lesion on DPCT

   12. Outcome measures Following parameters will be used to ascertain the outcome of treatment
   1. Primary Outcome

      1. Survival rate- calculated from the start of TACE
      2. End point Group 1 - Progression of disease and repeat TACE is not possible Group 2 - Death
   2. Secondary Outcome

      1. Tumor response on dual phase CECT
      2. Patient tolerance
      3. Childs' status of cirrhosis- will be ascertained at one and two years of follow up depending upon the Childs' scoreScore \<6- Childs'A, 7-9 Childs'B and \>10 Childs'C

Randomized Control Trial (RCT) of Transarterial Chemoembolization (TACE) Versus TACE and Oral Drug Therapy in the Treatment of Unresectable Hepatocellular Carcinoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Liver Resection for Patients With Hepatocellular Carcinoma and Impaired Liver Function	NCT06245785	Hepatic Cancer	transarterial c...	18 Years -	Tang-Du Hospital
Transarterial Chemoembolisation Plus Bevacizumab for Treatment of Hepatocellular Carcinoma	NCT00280007	Hepatocellular ...	bevacizumab	18 Years - 85 Years	Medical University of Vienna
TACE With Lenvatinib Versus Lenvatinib Alone in in First-line Treatment of Advanced HCC	NCT03905967	Advanced Hepato...	TACE Lenvatinib	18 Years - 75 Years	Sun Yat-sen University
RCT on Adjuvant TACE After Hepatectomy for HCC	NCT01512407	Hepatocellular ...	Transarterial c...	18 Years - 70 Years	Chinese University of Hong Kong
Liver Resection for Patients With Hepatocellular Carcinoma and Clinically Significant Portal Hypertension	NCT06245798	Hepatic Carcino...	transarterial c...	18 Years -	Tang-Du Hospital
Donafenib Plus Sintilimab in Combination With TACE in Patients With Unresectable Hepatocellular Carcinoma	NCT05507632	Unresectable He...	Donafenib plus ...	18 Years - 75 Years	Nanfang Hospital, Southern Medical University
Randomized Control Trial (RCT) of Transarterial Chemoembolization (TACE) Versus TACE and Oral Drug Therapy in the Treatment of Unresectable Hepatocellular Carcinoma	NCT00522405	Hepatocellular ...	TACE	12 Years - 80 Years	All India Institute of Medical Sciences, New Delhi
TACE With Lenvatinib Versus Lenvatinib Alone in in First-line Treatment of Advanced HCC	NCT03905967	Advanced Hepato...	TACE Lenvatinib	18 Years - 75 Years	Sun Yat-sen University
TACE With Lenvatinib Versus Lenvatinib Alone in in First-line Treatment of Advanced HCC	NCT03905967	Advanced Hepato...	TACE Lenvatinib	18 Years - 75 Years	Sun Yat-sen University

Spots Global Cancer Trial Database for transarterial chemoembolisation