Back to resultsSafety and Efficacy of RAD001 + TACE in Localized Unresectable HCC (TRACER)
Primary Purpose
Hepatocellular Carcinoma
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
everolimus
everolimus placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Localised, unresectable, chemoembolization
Eligibility Criteria
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
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
everolimus + TACE
placebo + TACE
Arm Description
everolimus 7.5mg/day by mouth + transcatheter arterial chemoembolization (TACE)
Placebo by mouth + transcatheter arterial chemoembolization (TACE)
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
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.
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.
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.
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.
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.
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01379521
Brief Title
Safety and Efficacy of RAD001 + TACE in Localized Unresectable HCC
Acronym
TRACER
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated due to low enrollment. This resulted in the study being underpowered and inconclusive.
Study Start Date
June 2011 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
June 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
Localised, unresectable, chemoembolization
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
65 (Actual)
8. Arms, Groups, and Interventions
Arm Title
everolimus + TACE
Arm Type
Experimental
Arm Description
everolimus 7.5mg/day by mouth + transcatheter arterial chemoembolization (TACE)
Arm Title
placebo + TACE
Arm Type
Placebo Comparator
Arm Description
Placebo by mouth + transcatheter arterial chemoembolization (TACE)
Intervention Type
Drug
Intervention Name(s)
everolimus
Other Intervention Name(s)
RAD001, Afinitor®)
Intervention Type
Drug
Intervention Name(s)
everolimus placebo
Primary Outcome Measure Information:
Title
Time to Progression (TTP) Based on the Modified RECIST Criteria
Description
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)
Time Frame
3, 6, 12, 18 and 24 months
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR) and Disease Control Rate (DCR) Based on the Modified RECIST
Description
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 Frame
6, 12 months, end of study
Title
Time to Progression Based on Original RECIST
Description
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.
Time Frame
6, 12 months, end of study
Title
Overall Response Rate (ORR) and Disease Control Rate (DCR) Based on Original RECIST
Description
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.
Time Frame
6, 12 months, end of study
Title
Overall Survival (OS)
Description
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.
Time Frame
6, 12, 18, 24, 30 months
Title
Incidences of Cumulative New Nodular Recurrence, Portal Vein Invasion and Extra Hepatic Metastases
Description
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.
Time Frame
30 months
Title
Percentage of Participants With a Decrease in the Sum of the of Longest Diameters (SLD) of Target Lesions From Baseline to 30 Months
Description
Percentage of participants with a decrease in the sum of the of longest diameters (SLD) of target lesions from Baseline to 30 months
Time Frame
baseline, 30 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Hong Kong
Country
Hong Kong
Facility Name
Novartis Investigative Site
City
Kaohsiung
ZIP/Postal Code
807
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Kaohsiung
ZIP/Postal Code
83301
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Lin-Kou
ZIP/Postal Code
33305
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Chiang Mai
ZIP/Postal Code
50200
Country
Thailand
12. IPD Sharing Statement
Learn more about this trial
Safety and Efficacy of RAD001 + TACE in Localized Unresectable HCC
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