Hepatocellular CarcinomaPhase 2TRACERNCT01379521
Safety and Efficacy of RAD001 + TACE in Localized Unresectable HCC
A Phase 2 study testing everolimus in people with Hepatocellular Carcinoma, run by Novartis Pharmaceuticals at 5 sites in 3 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- everolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 5 sitesin 3 countries
- Study dates
- Jun 2011to Jun 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
5 sites in 3 countries.
5 sites in 3 countries
Taiwan3 sites
Novartis Investigative Site
Kaohsiung, Taiwan, 83301
Novartis Investigative Site
Kaohsiung City, 807
Novartis Investigative Site
Linkou District, 33305
About this study
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
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).
- Conditions
- Hepatocellular Carcinoma
- Being tested
- everolimus, everolimus placebo
- Keywords
- Localised, unresectable, chemoembolization
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
everolimusDrug
Also called RAD001, Afinitor®)
everolimus placeboDrug
| Study group | Role | What they receive |
|---|---|---|
| everolimus + TACE | Experimental | everolimus 7.5mg/day by mouth + transcatheter arterial chemoembolization (TACE) Receives: Drug: everolimus |
| placebo + TACE | Placebo comparator | Placebo by mouth + transcatheter arterial chemoembolization (TACE) Receives: Drug: everolimus placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 3, 6, 12, 18 and 24 months
Secondary outcomes (6)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: baseline, 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2011 (estimated)
- Study startJun 2011
- Primary completionJun 2015
- Study completionJun 2015
Why it stopped: The study was terminated due to low enrollment. This resulted in the study being underpowered and inconclusive.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01379521
- Sponsor's protocol ID
- CRAD001OHK02
- Acronym
- TRACER
- Status last verified
- Apr 2017
- First submitted
- 1 Jun 2011
- Last updated
- 3 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01379521
- Acronym / sponsor ID
- TRACER / CRAD001OHK02
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Localised, unresectable, chemoembolization
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated due to low enrollment. This resulted in the study being underpowered and inconclusive.
- Enrolment
- 65 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jun 2011
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 23 Jun 2011 (estimated)
- Results
- Posted 3 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| everolimus + TACE | Experimental | Drug: everolimuseverolimus 7.5mg/day by mouth + transcatheter arterial chemoembolization (TACE) |
| placebo + TACE | Placebo comparator | Drug: everolimus placeboPlacebo by mouth + transcatheter arterial chemoembolization (TACE) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| everolimusAlso: RAD001, Afinitor®) | Drug | everolimus + TACE |
| everolimus placebo | Drug | placebo + TACE |
Primary outcome
Time to Progression (TTP) Based on the Modified RECIST Criteria
Time frame: 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)
6 secondary outcomes
Overall Response Rate (ORR) and Disease Control Rate (DCR) Based on the Modified RECIST
Time frame: 6, 12 months, end of study
Time to Progression Based on Original RECIST
Time frame: 6, 12 months, end of study
Overall Response Rate (ORR) and Disease Control Rate (DCR) Based on Original RECIST
Time frame: 6, 12 months, end of study
Overall Survival (OS)
Time frame: 6, 12, 18, 24, 30 months
Incidences of Cumulative New Nodular Recurrence, Portal Vein Invasion and Extra Hepatic Metastases
Time frame: 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
Time frame: baseline, 30 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
5 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing everolimus in people with Hepatocellular Carcinoma, run by Novartis Pharmaceuticals at 5 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Taiwan, Hong Kong, Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Progression (TTP) Based on the Modified RECIST Criteria (time frame: 3, 6, 12, 18 and 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2017.