Safety and Efficacy of RAD001 + TACE in Localized Unresectable HCC (TRACER)

A Phase II Randomized, Double-blinded, Multicenter Asian Study Investigating the Combination of Transcatheter Arterial Chemoembolization (TACE) and Oral Everolimus (RAD001, Afinitor®) in Localised Unresectable Hepatocellular Carcinoma (HCC) - The TRACER Study

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).

Study Overview

• Status: Terminated
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: everolimus; Drug: everolimus placebo

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Novartis Investigative Site
• Taiwan
  • Kaohsiung, Taiwan, 807
    • Novartis Investigative Site
  • Kaohsiung, Taiwan, 83301
    • Novartis Investigative Site
  • Lin-Kou, Taiwan, 33305
    • Novartis Investigative Site
• Thailand
  • Chiang Mai, Thailand, 50200
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: everolimus + TACE; everolimus 7.5mg/day by mouth + transcatheter arterial chemoembolization (TACE)	Drug: everolimus; Other Names: RAD001; Afinitor®)
PLACEBO_COMPARATOR: placebo + TACE; Placebo by mouth + transcatheter arterial chemoembolization (TACE)	Drug: everolimus placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Progression (TTP) Based on the Modified RECIST Criteria	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)	3, 6, 12, 18 and 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) and Disease Control Rate (DCR) Based on the Modified RECIST	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.	6, 12 months, end of study
Time to Progression Based on Original RECIST	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.	6, 12 months, end of study
Overall Response Rate (ORR) and Disease Control Rate (DCR) Based on Original RECIST	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.	6, 12 months, end of study
Overall Survival (OS)	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.	6, 12, 18, 24, 30 months
Incidences of Cumulative New Nodular Recurrence, Portal Vein Invasion and Extra Hepatic Metastases	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.	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	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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (ACTUAL): June 1, 2015
• Study Completion (ACTUAL): June 1, 2015

Study Registration Dates

• First Submitted: June 1, 2011
• First Submitted That Met QC Criteria: June 22, 2011
• First Posted (ESTIMATE): June 23, 2011

Study Record Updates

• Last Update Posted (ACTUAL): May 3, 2017
• Last Update Submitted That Met QC Criteria: April 13, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: chemoembolization; unresectable; Localised
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus
• Other Study ID Numbers: CRAD001OHK02