Clinical trial NCT03268499: Emulsion Versus Suspension in Chemoembolization for Hepatocellular Carcinoma
Official title: Ethiodized Oil-based Transarterial Chemoembolization for Patients With Hepatocellular Carcinoma: A Randomized Controlled Trial of Aqueous Cisplatin Emulsion Versus Anhydrous Cisplatin Suspension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hepatocellular Carcinoma
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2017-08-31
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: prospective, multi-center, parallel-group, open-label, phase III randomized control trial
Primary purpose: TREATMENT

Brief summary: The aim of the study was to evaluate the safety and efficacy of using the new formulation (Lipiodol-cisplatin suspension) for TACE in the treatment of HCC as compared to the conventional formulation (Lipiodol-cisplatin emulsion). This is a prospective, parallel-group, open-label randomized, phase III study that is conducted in accordance to the Declaration of Helsinki and international standards of Good Clinical Practice, and approved by the institutional review board. Eligible patients were randomized into either a treatment arm of Lipiodol-cisplatin suspension or a control arm of Lipiodol-cisplatin emulsion with a 1:1 ratio.

Detailed description: Randomization with 1:1 ratio is centralized and performed by an independent statistician, it is stratified by the diameter of largest tumor less than or equal to 5cm or \> 5cm, and total number of tumors less than or equal to 3 or \> 3. Random permuted block method with block size of 4 to 6 is used according to a computer-generated allocation sequence. The patients, doctors and other caretakers are not blinded to group allocation. Data collectors and analysts who assess the study outcome and radiologists who assess tumor response are blinded to group allocation.

Assuming the complete response rates in the Suspension Group and Emulsion Group are 70% and 35% respectively, 85% power and 5% level of confidence, the sample size is estimated to be 70 (35 for each arm). Assuming 10 subjects to be withdrawn from the study or lost to follow-up, the final sample size is estimated to be 80.

Eligibility criteria: Inclusion criteria

1. Written informed consent
2. Age above 18 years
3. HCC unsuitable for resection or ablation
4. Child-Pugh A cirrhosis
5. Eastern Cooperative Oncology Group performance score 0 or 1
6. BCLC A or B
7. No previous treatment for HCC except for liver resection
8. HCC diagnosed by typical enhancement patterns on cross sectional imaging or histology.
9. No extra-hepatic involvement on non-enhanced CT thorax and triphasic contrast enhanced CT abdomen.
10. No invasion of portal vein or hepatic vein
11. Massive expansive tumor morphology with measurable lesion on CT (characterized by well-defined spherical or globular configuration, with or without tumor capsule or satellite lesions)
12. Total tumor mass \< 50% liver volume
13. Size of any individual tumor greater than or equal to 10cm in largest dimension
14. Serum creatinine \< 130 umol/L or Creatinine clearance \> 55 ml/min.

Exclusion criteria

1. Known active malignancy within the last 3 years
2. History of acute tumor rupture presenting with hemo-peritoneum
3. Biliary obstruction not amenable to percutaneous or endoscopic drainage
4. History of hepatic encephalopathy
5. Intractable ascites not controllable by medical therapy
6. History of variceal bleeding within last 3 months
7. Infiltrative tumor morphology (characterized by ill- defined tumor margin and amorphous configuration) or diffuse tumor morphology (characterized by large number of small nodules)
8. Un-correctable Arterio-portal venous shunt affecting \>1 hepatic segment on CT
9. Arterial-hepatic venous shunt with hepatic vein opacified in arterial phase on CT

Primary outcomes:
measure: Number of Paticipants With Complete Tumor Response After the First 3 Treatments
timeFrame: Within 6 months after randomization
measure: Number of Participants With Severe Adverse Events of All Treatment Procedures Occurring Within 30 Days of the Treatment
timeFrame: within 30 days of the treatment
Secondary outcomes:
measure: Number of Paticipants With Complete Tumour Response After the First Treatment
timeFrame: At 3 months after the first treatment
measure: Number of Participants With Complete or Partial Tumour Response at 6 Months
timeFrame: At 6 months after the first treatment
measure: Number of Participants With Intralesional Tumour Progression From Randomization Date up to 78 Months
timeFrame: throughout follow-up period, up to 78 months
measure: Number of Participants With Extralesional Tumour Progression From Randomization Date up to 78 Months
timeFrame: throughout follow-up period, up to 78 months
measure: Number of Participants With Extrahepatic Tumour Progression up to 78 Months
timeFrame: throughout follow-up period, up to 78 months
measure: Time Interval in Months From Randomization Date to Occurrence of Any Kind of Tumor Progression up to 78 Months
timeFrame: throughout follow-up period, up to 78 months
measure: Progression Free Survival in Number of Months up to 78 Months
timeFrame: throughout follow-up period, up to 78 months
measure: Overall Survival in Months up to 78 Months
timeFrame: throughout follow-up period, up to 78 months
measure: Adverse Event
timeFrame: Within 30 days after the first treatment
measure: Serious Adverse Event
timeFrame: Within 30 days after all treatments
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong
Study officials:
affiliation: DIIR, CUHK, Hong Kong
name: Simon Yu
role: PRINCIPAL_INVESTIGATOR
References: