Trial Outcomes & Findings for Emulsion Versus Suspension in Chemoembolization for Hepatocellular Carcinoma (NCT NCT03268499)

NCT ID: NCT03268499

Last Updated: 2024-11-15

Results Overview

Complete tumor response is defined according to the Modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria as well as DSA findings during the second and third treatment, it is defined as the absence of enhancing tumor on CT and/ or absence of residual tumor on selective DSA of the feeding arteries to the tumors and absence of enhancing tumor on the subsequent CT.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 80 participants
• Primary outcome timeframe: Within 6 months after randomization
• Results posted on: 2024-11-15

Participant Flow

Recruitment period: September 2016 to August 2022 Recruitment took place in the surgery and oncology clinics of three general hospitals including Prince of Wales Hospital, United Christian Hospital and Tuen Mun Hospital in Hong Kong

Of all 2772 new HCC patients who attended the three hospitals from September 2016 to August 2022, 862 patients who refused or were considered unsuitable for liver resection or ablation were screened, 782 patients were excluded due to failing to meet the eligibility criteria (97%) or having declined to participate (3%).

Participant milestones

Measure	Emulsion Group Patients are treated with chemoembolization using a formulation that consists of 10mg aqueous cisplatin (10mL) mixed with 10mL Lipiodol to form an emulsion (0.5mg cisplatin/mL emulsion) Lipiodol-based transarterial chemoembolization: Arterial catheterization to segmental, subsegmental, or sub-subsegmental level was achieved depending on the tumor size, to gain arterial access as close to the tumors as possible. The formulation was delivered under fluoroscopic control until the vasculature of all tumors was entirely filled, or until the maximum dose was reached.	Suspension Group Patients are treated with chemoembolization using a formulation that consists of a suspension of 100mg pure anhydrous cisplatin in 20mL Lipiodol (5mg cisplatin /mL suspension) Lipiodol-based transarterial chemoembolization: Arterial catheterization to segmental, subsegmental, or sub-subsegmental level was achieved depending on the tumor size, to gain arterial access as close to the tumors as possible. The formulation was delivered under fluoroscopic control until the vasculature of all tumors was entirely filled, or until the maximum dose was reached.
Overall Study STARTED	40	40
Overall Study COMPLETED	38	39
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Measure	Emulsion Group Patients are treated with chemoembolization using a formulation that consists of 10mg aqueous cisplatin (10mL) mixed with 10mL Lipiodol to form an emulsion (0.5mg cisplatin/mL emulsion) Lipiodol-based transarterial chemoembolization: Arterial catheterization to segmental, subsegmental, or sub-subsegmental level was achieved depending on the tumor size, to gain arterial access as close to the tumors as possible. The formulation was delivered under fluoroscopic control until the vasculature of all tumors was entirely filled, or until the maximum dose was reached.	Suspension Group Patients are treated with chemoembolization using a formulation that consists of a suspension of 100mg pure anhydrous cisplatin in 20mL Lipiodol (5mg cisplatin /mL suspension) Lipiodol-based transarterial chemoembolization: Arterial catheterization to segmental, subsegmental, or sub-subsegmental level was achieved depending on the tumor size, to gain arterial access as close to the tumors as possible. The formulation was delivered under fluoroscopic control until the vasculature of all tumors was entirely filled, or until the maximum dose was reached.
Overall Study Withdrawal by Subject	2	1

Baseline Characteristics

Emulsion Versus Suspension in Chemoembolization for Hepatocellular Carcinoma

Baseline characteristics by cohort

Measure	Suspension Group n=39 Participants Received TACE using suspension formulation	Emulsion Group n=38 Participants Received TACE using emulsion formulation	Total n=77 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=5 Participants	14 Participants n=7 Participants	27 Participants n=5 Participants
Age, Categorical >=65 years	26 Participants n=5 Participants	24 Participants n=7 Participants	50 Participants n=5 Participants
Age, Continuous	70 years n=5 Participants	68 years n=7 Participants	68 years n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	5 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	33 Participants n=7 Participants	59 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	39 Participants n=5 Participants	38 Participants n=7 Participants	77 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Hong Kong	39 participants n=5 Participants	38 participants n=7 Participants	77 participants n=5 Participants

PRIMARY outcome

Timeframe: Within 6 months after randomization

Complete tumor response is defined according to the Modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria as well as DSA findings during the second and third treatment, it is defined as the absence of enhancing tumor on CT and/ or absence of residual tumor on selective DSA of the feeding arteries to the tumors and absence of enhancing tumor on the subsequent CT.

Outcome measures

Measure	Suspension Group n=39 Participants complete tumor response after the first 3 treatments	Emulsion Group n=38 Participants complete tumor response after the first 3 treatments
Number of Paticipants With Complete Tumor Response After the First 3 Treatments	35 Participants	18 Participants

PRIMARY outcome

Timeframe: within 30 days of the treatment

Severe adverse events is defined as any undesirable symptom, sign or medical condition which was fatal or life-threatening, required or prolonged hospitalization, resulted in persistent or significant disability/incapacity, or was medically significant, might jeopardize the patient and might require medical or surgical intervention.

Outcome measures

Measure	Suspension Group n=39 Participants complete tumor response after the first 3 treatments	Emulsion Group n=38 Participants complete tumor response after the first 3 treatments
Number of Participants With Severe Adverse Events of All Treatment Procedures Occurring Within 30 Days of the Treatment	2 Participants	7 Participants

SECONDARY outcome

Timeframe: At 3 months after the first treatment

Complete tumor response is defined according to the Modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria as well as DSA findings during the second and third treatment, it is defined as the absence of enhancing tumor on CT and/ or absence of residual tumor on selective DSA of the feeding arteries to the tumors and absence of enhancing tumor on the subsequent CT.

Outcome measures

Measure	Suspension Group n=39 Participants complete tumor response after the first 3 treatments	Emulsion Group n=38 Participants complete tumor response after the first 3 treatments
Number of Paticipants With Complete Tumour Response After the First Treatment	22 Participants	4 Participants

SECONDARY outcome

Timeframe: At 6 months after the first treatment

Objective tumor response was defined as complete response or partial response. Partial response was defined by the modified RECIST criteria as at least a 30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions

Outcome measures

Measure	Suspension Group n=39 Participants complete tumor response after the first 3 treatments	Emulsion Group n=38 Participants complete tumor response after the first 3 treatments
Number of Participants With Complete or Partial Tumour Response at 6 Months	39 Participants	27 Participants

SECONDARY outcome

Timeframe: throughout follow-up period, up to 78 months

Population: 2 participants excluded from analysis in each group since the patients received liver resection

Intralesional tumor progression is defined as tumor recurrence at the site of treated tumor after initial complete tumor response, or any degree of enlargement of treated tumor after initial partial response;

Outcome measures

Measure	Suspension Group n=37 Participants complete tumor response after the first 3 treatments	Emulsion Group n=36 Participants complete tumor response after the first 3 treatments
Number of Participants With Intralesional Tumour Progression From Randomization Date up to 78 Months	5 Participants	17 Participants

SECONDARY outcome

Timeframe: throughout follow-up period, up to 78 months

Extralesional tumor progression is defined as occurrence of new tumor at a new site of the liver;

Outcome measures

Measure	Suspension Group n=37 Participants complete tumor response after the first 3 treatments	Emulsion Group n=36 Participants complete tumor response after the first 3 treatments
Number of Participants With Extralesional Tumour Progression From Randomization Date up to 78 Months	12 Participants	20 Participants

SECONDARY outcome

Timeframe: throughout follow-up period, up to 78 months

Extrahepatic tumor progression is defined as occurrence of venous invasion by tumor or extrahepatic tumor metastasis;

Outcome measures

Measure	Suspension Group n=37 Participants complete tumor response after the first 3 treatments	Emulsion Group n=36 Participants complete tumor response after the first 3 treatments
Number of Participants With Extrahepatic Tumour Progression up to 78 Months	3 Participants	3 Participants

SECONDARY outcome

Timeframe: throughout follow-up period, up to 78 months

Any kind of tumor progression include intralesional progression, extralesional progression, or extrahepatic progression

Outcome measures

Measure	Suspension Group n=37 Participants complete tumor response after the first 3 treatments	Emulsion Group n=36 Participants complete tumor response after the first 3 treatments
Time Interval in Months From Randomization Date to Occurrence of Any Kind of Tumor Progression up to 78 Months	24.6 months Interval 13.3 to 38.9	10.7 months Interval 7.5 to 14.1

SECONDARY outcome

Timeframe: throughout follow-up period, up to 78 months

Progression free survival is defined as the interval between the randomization date and the date of any kind of tumor progression or death from any cause;

Outcome measures

Measure	Suspension Group n=37 Participants complete tumor response after the first 3 treatments	Emulsion Group n=36 Participants complete tumor response after the first 3 treatments
Progression Free Survival in Number of Months up to 78 Months	21.1 months Interval 14.3 to 38.9	10.4 months Interval 7.3 to 13.4

SECONDARY outcome

Timeframe: throughout follow-up period, up to 78 months

Overall survival Overall survival is defined as the interval between the randomization date and the date of death from any cause. In the absence of confirmation of death, survival time was censored at the last date the patient was known to be alive;

Outcome measures

Measure	Suspension Group n=37 Participants complete tumor response after the first 3 treatments	Emulsion Group n=36 Participants complete tumor response after the first 3 treatments
Overall Survival in Months up to 78 Months	53.3 months Interval 40.5 to 80.0	36 months Interval 25.7 to 46.6

SECONDARY outcome

Timeframe: Within 30 days after the first treatment

Number of participants with the specific adverse event that occurred within 30 days after the first treatment

Outcome measures

Measure	Suspension Group n=39 Participants complete tumor response after the first 3 treatments	Emulsion Group n=38 Participants complete tumor response after the first 3 treatments
Adverse Event Fever	30 Participants	32 Participants
Adverse Event Nausea	14 Participants	8 Participants
Adverse Event Vomiting	13 Participants	10 Participants
Adverse Event Abdominal pain	25 Participants	26 Participants
Adverse Event bilirubin elevation	32 Participants	37 Participants
Adverse Event albumin depression	33 Participants	30 Participants
Adverse Event Alkaline phosphatase elevation	31 Participants	33 Participants
Adverse Event Alanine aminotransferase	39 Participants	33 Participants

SECONDARY outcome

Timeframe: Within 30 days after all treatments

Serious adverse event that occurs within 30 days after all treatments

Outcome measures

Measure	Suspension Group n=39 Participants complete tumor response after the first 3 treatments	Emulsion Group n=38 Participants complete tumor response after the first 3 treatments
Serious Adverse Event	2 Participants	7 Participants

Adverse Events

Suspension Group

Serious events: 2 serious events

Other events: 39 other events

Deaths: 10 deaths

Emulsion Group

Serious events: 7 serious events

Other events: 38 other events

Deaths: 16 deaths

Serious adverse events

Measure	Suspension Group n=39 participants at risk Details are provided under "Adverse events" in secondary endpoints.	Emulsion Group n=38 participants at risk Details are provided under "Adverse events" in secondary endpoints.
Hepatobiliary disorders Death	0.00% 0/39 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.	2.6% 1/38 • Number of events 1 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.
Hepatobiliary disorders Liver abscess	2.6% 1/39 • Number of events 1 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.	10.5% 4/38 • Number of events 4 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.
Hepatobiliary disorders Biliary sepsis	2.6% 1/39 • Number of events 1 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.	0.00% 0/38 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.
Gastrointestinal disorders Bleeding varices	0.00% 0/39 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.	2.6% 1/38 • Number of events 1 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.
Hepatobiliary disorders Liver failure	2.6% 1/39 • Number of events 1 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.	2.6% 1/38 • Number of events 1 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.
Gastrointestinal disorders Gastritis	0.00% 0/39 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.	2.6% 1/38 • Number of events 1 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.

Other adverse events

Measure	Suspension Group n=39 participants at risk Details are provided under "Adverse events" in secondary endpoints.	Emulsion Group n=38 participants at risk Details are provided under "Adverse events" in secondary endpoints.
General disorders Fever	76.9% 30/39 • Number of events 30 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.	84.2% 32/38 • Number of events 32 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.
General disorders Nausea	35.9% 14/39 • Number of events 14 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.	21.1% 8/38 • Number of events 8 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.
General disorders Vomiting	33.3% 13/39 • Number of events 13 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.	26.3% 10/38 • Number of events 10 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.
Hepatobiliary disorders Abdominal pain	64.1% 25/39 • Number of events 25 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.	68.4% 26/38 • Number of events 26 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.
Hepatobiliary disorders Bilirubin elevation	82.1% 32/39 • Number of events 32 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.	97.4% 37/38 • Number of events 37 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.
Hepatobiliary disorders Albumin depression	84.6% 33/39 • Number of events 33 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.	78.9% 30/38 • Number of events 30 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.
Hepatobiliary disorders Alkaline phosphatase elevation	79.5% 31/39 • Number of events 31 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.	86.8% 33/38 • Number of events 33 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.
Hepatobiliary disorders Alanine aminotransferase elevation	100.0% 39/39 • Number of events 39 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.	86.8% 33/38 • Number of events 33 • Up to 78 months after randomization Details of "Adverse events" are being reported under secondary endpoints. "All-cause mortality", details of "Serious Adverse Events", and "Other Adverse Events" are being reported here.

Additional Information

Simon Chun Ho Yu

The Chinese University of Hong Kong

Phone: +852 35051035

Email: simonyu@cuhk.edu.hk

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place