Efficacy and Safety Doxorubicin Transdrug Study in Patients Suffering From Advanced Hepatocellular Carcinoma

OS is defined as the time from date of randomization to the date of death from any cause.

Time frame: Time from date of randomization to the date of death from any cause with initial assessment up to 24 months and follow-up assessment up to 45 months.

Population: Intent-to-treat (ITT) Population: All randomized patients. The DT at 20 mg/m2 and 30 mg/m2 are combined into DT pooled experimental group for comparison with the BSC group. The primary analysis per protocol is DT pooled versus BSC and not individual DT groups.

ORR is defined as percent of patients whose best overall response is complete response (CR) or partial response (PR) during the study treatment period and based on the evaluation of independent radiological review according to RECIST 1.1 for target lesions and assessed by MRI: CR is disappearance of all targets extra nodal lesions and the regression of all nodal lesions to \< 10 mm; PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of diameters while on study. PD is at least a 20% increase in the sum of diameters of target lesions, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is considered progression.

Time frame: Time from date of first treatment cycle to date of last cycle of treatment for the full duration of study treatment up to 24 months.

Population: ITT population: all randomized patients. The DT at 20 mg/m2 and 30 mg/m2 are combined into DT pooled experimental group for comparison with the BSC group. The primary analysis is the DT pooled versus BCS. This was only analyzed for the initial study.

PFS is defined as time from the date of randomisation to the date of the first documented progression or death from any cause. PFS determined by independent radiological review according to Response Evaluation Criteria In Solid Tumour (RECIST) 1.1 is determine by at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is considered progression.

Time frame: Time from date of randomization to date of first documented progression or death from any cause, which ever came first, assessed up to 20 months.

Population: ITT population: All randomized patients. The DT at 20 mg/m2 and 30 mg/m2 are combined into DT pooled experimental group for comparison with the BSC group. The primary analysis is DT pooled versus BSC. This was only analyzed for the initial study.

Number of participants experiencing an SaO2 reduction defined as a decrease =\< 90% during or after DT infusion until resolution to =\>93%. Participants had continuous monitoring of SaO2 saturation with pulse oximeter during 6 hour infusion and up to 24 hour after infusion start. SaO2 measures the amount of oxygen (in percent) bound to hemoglobin in red blood cells. SaO2 saturation was only monitored and reported in the DT infusion group. Reduction in SaO2 could result in modify DT dosing regimen. Decreases in SaO2 are a known and expected occurrence with DT infusions, and close monitoring of SaO2 was specified by the protocol to protect patients from potential respiratory distress during infusions.

Time frame: Time from start of infusion to resolution of reduction in oxygen saturation.

Population: Safety population: All patients receiving at least one infusion for DT groups.

Number of participants experiencing clinically significant abnormal ECG changes from baseline over the course of the study. ECG were completed every month before each infusion. ECG will detect changes in heart rhythm. Clinically significant abnormal changes in ECG were determined by the investigator.

Time frame: Time from baseline assessment to time of death, disease progression, or withdrawal of patient from the study.

Population: Safety Population: All patients receiving at least one infusion for DT groups and all patients for BSC group whatever treatment they received.

Number of participants that experienced a change from baseline in LVEF with severity of LVEF noted as follows: Normal: 100 - 50%, 0 - 9% drop from baseline resting ejection fraction (EF), Grade 2 = 50 - 40%, 10 - 19% drop from baseline resting EF; Grade 3 = 39 - 20%, \>20% drop from baseline; Grade 4 = \<20%. LVEF was monitored every other month. LVEF measures how much blood the left ventricle of the heart pumps out with each contraction and is used to assess the severity of left ventricle dysfunction in the heart. Clinical significance changes were determined by the investigator.

Time frame: Time from baseline assessment to time of death, disease progression, or withdrawal of patient from the study.

Population: Safety Population: All patients receiving at least one infusion for DT groups and all patients for BSC group whatever treatment they received.

The number of participants experiencing TEAEs considered related to treatment and categorized by severity of all related TEAEs according to National Cancer Institute/Common Toxicity Criteria (NCI-CTCAE) v4.0 and resulting in patient withdrawal from study or death.

Time frame: Time from date of initial treatment to date of death, disease progression, or participant withdrawal from the study.

Population: Safety Population: All patients receiving at least one infusion for DT groups and all patients for BSC group whatever treatment they received.

The number of participants with cardiovascular and respiratory adverse events (AEs) were assessed according to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) criteria version 4.0, using the Medical Dictionary for Regulatory Activities (MedDRA). The AE numbers reported are those considered related to treatment. Related AEs are those that are judged unlikely, possibly, probably or definitely related to the study or study drug by the investigator.

Time frame: Time from date of initial treatment to date of death, disease progression, or patient withdrawal from the study.

Population: Safety Population: All patients receiving at least one infusion for DT groups and all patients for BSC group whatever treatment they received.

Number of participants with any clinically significant abnormal change in respiratory function test over the study to include carbon monoxide diffusing capacity to measure lung function, forced expiratory volume in 1 second to measure ability to expel air from your lungs, total lung capacity to measure total amount of air in the lungs after taking the deepest breath possible, and vital capacity to measure the greatest volume of air that can be expelled from the lungs after taking the deepest breath possible. Clinically significant abnormal changes in respiratory function was determined by the investigator.

Time frame: Time from baseline assessment to time of death, disease progression, or withdrawal of patient from the study.

Population: Safety Population: All patients receiving at least one infusion for DT groups and all patients for BSC group whatever treatment they received.