Safety and Efficacy of RAD001 + TACE in Localized Unresectable HCC

Phase 2

Terminated

Conditions: Hepatocellular Carcinoma

Interventions: Drug: everolimus placebo
Drug: everolimus

Registration Number: NCT01379521

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: This study will evaluate the role of everolimus in combination with local Transcatheter Arterial Chemoembolization (TACE) procedure in patients with localized unresectable Hepatocellular Carcinoma (HCC).

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 65

Inclusion Criteria

Newly diagnosed hepatocellular carcinoma limited to liver and not suitable for resection, liver transplant, or radiofrequency ablation.
Intermediate stage (stage B) (according to recognized guidelines) and suitable for TACE therapy
At least one nodule between > 2cm and ≤ 15cm in diameter with no vascular invasion or abdominal lymph node or distant metastases.
Must have 1 tumor which can be measured in 1 dimension according to specified criteria (RECIST and mRECIST) and has not previously been treated with any type of therapy.
ECOG performance status < 2cm
Cirrhotic status of Child-Pugh class A or early B
HBV-DNA or HBsAg positive at screen or baseline: preventative treatment with anti-viral started 1-2 weeks prior to receiving study drug

Exclusion Criteria

Any local and/or investigational drugs within 28 days prior to randomization
Active bleeding during the last 28 days prior to screening including variceal bleeding
Prior therapy with mTOR inhibitors
Tumor burden of > 60% liver involvement
Prior systemic or local therapy including TACE except for the first TACE at Day 0), surgery or liver transplantation
Failed first TACE at Day 0, Cycle 1 for any reason
Known history of human immunodeficiency virus (HIV) seropositivity (HIV testing is not mandatory)
Alcohol intake of 80 grams per day
Undergone major surgery ≤ 3 weeks prior to starting study drug or who have not recovered from surgery
Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods

Other protocol-defined inclusion/exclusion criteria may apply

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
placebo + TACE	everolimus placebo	Placebo by mouth + transcatheter arterial chemoembolization (TACE)
everolimus + TACE	everolimus	everolimus 7.5mg/day by mouth + transcatheter arterial chemoembolization (TACE)

Primary Outcome Measures

Name	Time	Method
Time to Progression (TTP) Based on the Modified RECIST Criteria	3, 6, 12, 18 and 24 months	Time to Progression (TTP) defined as the time from the date of randomization to the date of first documented radiological confirmation of disease progression based on modified RECIST criteria. Progressive Disease: \>20% increase in sum of the longest diameters (SLD) of "viable" target lesion (arterial phase enhancement)

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR) and Disease Control Rate (DCR) Based on the Modified RECIST	6, 12 months, end of study	Overall response rate was defined as the number of patients whose best overall response was either complete response or partial response according to the modified RECIST. Complete response: Disappearance of arterial phase enhance-ment in all target lesions. Partial response: \>30% decrease in sum of the longest diameters (SLD) of "viable" target lesion (arterial phase enhance-ment)Disease control rate was defined as the number of patients with a best overall response of complete response, partial response or stable disease. The study was terminated early due to slow enrollment of 4 years, higher than anticipated screen failure rate due to a higher than anticipated proportion of patients having advanced liver disease and a change in clinical practice the total of 80 patients was not reached with only 59 patients recruited in total. The study was underpowered due to termination therefore data was not collected and the outcome measure was not analyzed.
Time to Progression Based on Original RECIST	6, 12 months, end of study	Time to Progression (TTP) defined as the time from the date of randomization to the date of first documented radiological confirmation of disease progression based on original RECIST criteria. Progressive Disease: \>20% increase in sum of the longest diameters (SLD) of target lesions with an absolute increase of ≥5 mm; new lesions. The study was terminated early due to slow enrollment of 4 years, higher than anticipated screen failure rate due to a higher than anticipated proportion of patients having advanced liver disease and a change in clinical practice the total of 80 patients was not reached with only 59 patients recruited in total. The study was underpowered due to termination therefore data was not collected and the outcome measure was not analyzed.
Overall Response Rate (ORR) and Disease Control Rate (DCR) Based on Original RECIST	6, 12 months, end of study	Overall response rate was defined as the number of patients whose best overall response was either complete response or partial response according to the Complete response: Disappearance of all target lesions or lymph nodes \<10 mm in the short axis Partial response: \>30% decrease in sum of the longest diameters (SLD) of target lesions Disease control rate was defined as the number of patients with a best overall response of complete response, partial response or stable disease. The study was terminated early due to slow enrollment of 4 years, higher than anticipated screen failure rate due to a higher than anticipated proportion of patients having advanced liver disease and a change in clinical practice the total of 80 patients was not reached with only 59 patients recruited in total. The study was underpowered due to termination therefore data was not collected and the outcome measure was not analyzed.
Overall Survival (OS)	6, 12, 18, 24, 30 months	Overall survival was defined as the time from date of randomization to date of death due to any cause. If death had not occurred at the date of the analysis cut-off then OS was censored at the date of the last contact.
Incidences of Cumulative New Nodular Recurrence, Portal Vein Invasion and Extra Hepatic Metastases	30 months	Incidences of cumulative new nodular recurrence, portal vein invasion and extra hepatic metastases but incidence of portal vein invasion meant those patients without documented vascular invasion at screening/baseline. The study was terminated early due to slow enrollment of 4 years, higher than anticipated screen failure rate due to a higher than anticipated proportion of patients having advanced liver disease and a change in clinical practice the total of 80 patients was not reached with only 59 patients recruited in total. The study was underpowered due to termination therefore data was not collected and the outcome measure was not analyzed.
Percentage of Participants With a Decrease in the Sum of the of Longest Diameters (SLD) of Target Lesions From Baseline to 30 Months	baseline, 30 months	Percentage of participants with a decrease in the sum of the of longest diameters (SLD) of target lesions from Baseline to 30 months