Carcinoma, HepatocellularPhase 4NCT02081755
Safety and Efficacy of Everolimus Treatment in Liver Transplantation for Liver Cancer
A Phase 4 study testing Everolimus, Tacrolimus and Myfortic in people with Carcinoma, Hepatocellular, run by Baylor Research Institute at 9 sites in United States.
Trial summary
This study is a prospective Phase IV study to determine if the use of Everolimus results in lower liver tumor recurrence and improved patient and graft survival after liver transplant for hepatocellular carcinoma (HCC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Hepatocellular
- What is being tested?
- Everolimus, Tacrolimus and Myfortic
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 336 participants
- Where
- 9 sitesUnited States
- Study dates
- Mar 2014to Mar 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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
Screening Inclusion Criteria:
- Have a diagnosis of hepatocellular carcinoma (HCC) and high risk for HCC recurrence
- Able to provide written informed consent
- Male and female patients of any race, 18 years or older
- De novo recipients of a primary orthotopic liver transplant from a deceased or living donor
- Patients willing to comply with study requirements
- Women of child-bearing potential (WOCBP) must agree to use an effective method(s) of contraception during treatment and during the post treatment follow-up period
Screening Exclusion Criteria:
- Past or present malignancy within the last 5 years.
- Severe infection considered by the local site investigator to be unsafe for study participation.
- Use of other investigational drugs at the time of screening or within the last 30 days.
- Patients scheduled for a combined transplant (such as liver-kidney), or having a previous solid organ, bone marrow, or autologous islet cell transplant.
- Recipients of donor/recipient ABO incompatible grafts.
- Recipients of organs from human immunodeficiency virus (HIV) or HBsAg positive donors.
- Macrovascular tumor invasion.
- Proteinuria greater than 2 grams/24 hours.
- Conditions which can result in impaired absorption, distribution, metabolism or excretion of the study treatment.
- Patients with non-infectious pneumonitis.
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
- Women of child-bearing potential (WOCBP) not practicing an effective method(s) of contraception.
- Patients who receive sirolimus (Rapamune®) as part of their transplant immunosuppression regimen
Randomization Screening Inclusion Criteria :
- For patients with a history of any hepatic vessel thrombosis, occlusion, stent placement, or major revision of liver vessels, must have a Doppler ultrasound prior to randomization to rule out any hepatic vessel complication, including hepatic arterial thrombosis (HAT).
Randomization Exclusion Criteria:
- Patients who receive sirolimus (Rapamune) any time prior to randomization will be withdrawn from the study.
- Patients who develop clinically significant systemic infections requiring active use of IV antibiotics any time prior to randomization.
- Wound healing problem, per Investigator's assessment, that would make the patient ineligible for study randomization
- Confirmed presence of a thrombosis in a major hepatic artery(s), major hepatic vein(s), portal vein or inferior vena cava via Doppler ultrasound or other imaging obtained prior to randomization.
- Proteinuria greater than 2 grams/24 hours.
- Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive everolimus or be randomized into the study.
Trial locations and contacts
9 sites in 1 country. Contact the study team or a site near you to ask about taking part.
9 sites in 1 country
United States9 sites
Northwestern University School of Medicine
Chicago, Illinois, 60611
Baylor University Medical Center
Dallas, Texas, 75246
University of Kansas Medical Center
Kansas City, Kansas, 66160
University of Tennessee- Methodist University Hospital
Memphis, Tennessee, 38104
Mount Sinai Medical Center
New York, New York, 10029
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Mayo Clinic
Rochester, Minnesota, 55905
University of California at San Francisco
San Francisco, California, 94143
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A 36 Month Multi-center, Open Label, Randomized, Comparator Study to Evaluate the Efficacy and Safety of Everolimus Immunosuppression Treatment in Liver Transplantation for Hepatocellular Carcinoma Exceeding Milan Criteria
This study is a prospective Phase IV study to determine if the use of Everolimus results in lower liver tumor recurrence and improved patient and graft survival after liver transplant for hepatocellular carcinoma (HCC). The immunosuppressive comparators will be Everolimus and Tacrolimus therapy compared to Tacrolimus and Mycophenolic acid/Mycophenolate Mofetil/Azathioprine. Primary outcomes data is disease free survival (the time from randomization to HCC recurrence or death). Secondary outcomes are rate of recurrence of Hepatitis C, problems related to wound healing, hernia repair within the first 12 months, hepatic arterial thrombosis, renal function, acute cellular rejection, post-transplant diabetes, hypertension, and hyperlipidemia.
Read the detailed description
The study population will consist of approximately 336 patients (224 Everolimus and Tacrolimus and 112 Tacrolimus and Mycophenolic acid/Mycophenolate Mofetil/Azathioprine). Initial screening criteria will include the presence of hepatocellular carcinoma in patients 18 years or older who are candidates to receive a primary orthotopic liver transplant (from deceased or living donor). Within 7 - 12 days post-transplant, patients will be re-evaluated for eligibility for randomization. The criteria include: pre-transplant imaging that shows HCC disease exceeding Milan criteria; pathology review for tumor burden and/or presence of microvascular invasion; AFP >200IU/mL; pre-transplant ablation or resection with HCC recurrence; progression or new tumors; evaluation to rule out any hepatic vessel complication.
Subjects will remain in study treatment until Month 12 at which time the subject and investigator will determine the preferred immunosuppressive regimen. Subjects will be followed for an additional 24 months for outcome data as described above.
- Conditions
- Carcinoma, Hepatocellular
- Being tested
- Everolimus, Tacrolimus, Myfortic, CellCept, Imuran
- Keywords
- Immunosuppressive Agents, Liver Transplantation
- 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 Zortress, Afinitor
Everolimus Dosing: 1.5 mg BID (3.0 mg/day) for 12 months
TacrolimusDrug
Also called Prograf
Tacrolimus Dosing: 0.05 mg/kg BID for 12 months
MyforticDrug
Also called Mycophenolic Acid
Myfortic®: 360 mg to 1080 mg BID for 12 months
CellCeptDrug
Also called Mycophenolate Mofetil
CellCept: 500 mg to 1500 mg BID for 12 months
ImuranDrug
Also called Azathioprine
0.5 mg/kg to 2 mg/kg QD for 12 months
| Study group | Role | What they receive |
|---|---|---|
| Everolimus and Tacrolimus | Experimental | Everolimus Dosing: 1.5 mg BID (3.0 mg/day) Tacrolimus Dosing: 0.05 mg/kg BID Receives: Drug: Everolimus; Drug: Tacrolimus |
| Tacrolimus and Myfortic or CellCept or Imuran | Active comparator | Myfortic: 360 mg to 1080 mg BID OR CellCept: 500 mg to 1500 mg BID OR Imuran: 0.5mk/kg to 2mg/kg QD AND Tacrolimus Dosing: 0.05 mg/kg BID Receives: Drug: Tacrolimus; Drug: Myfortic; Drug: CellCept; Drug: Imuran |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease free survival (DFS) defined as the time from randomization to the time of tumor recurrence or death, whichever occurs first.
Measured: Through Month 36
Secondary outcomes (10)
Tumor recurrence sites
Measured: Through Month 36
Hepatitis C recurrence rate
Measured: Through Month 36
Renal function
Measured: Through Month 36
Acute cellular rejection
Measured: Through Month 36
Post-transplant diabetes
Measured: Through Month 36
Hypertension
Measured: Through Month 36
Hyperlipidemia
Measured: Through Month 36
Wound healing and associated risk factors
Measured: Through Month 36
Hernia repair
Measured: Through Month 36
Hepatic arterial thrombosis
Measured: Through Month 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2014 (estimated)
- Study startMar 2014
- Primary completionMar 2027 (estimated)
- Study completionMar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, HepatocellularStudies of the same condition, open and under way.
- More trials run by Baylor Research InstituteThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 336 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Baylor Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Goran Klintmalm, MD, PhD, Principal investigator, Baylor Health Care System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02081755
- Sponsor's protocol ID
- 013-307
- Status last verified
- Jan 2026
- First submitted
- 5 Mar 2014
- Last updated
- 27 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 36 Month Multi-center, Open Label, Randomized, Comparator Study to Evaluate the Efficacy and Safety of Everolimus Immunosuppression Treatment in Liver Transplantation for Hepatocellular Carcinoma Exceeding Milan Criteria
- ClinicalTrials.gov ID
- NCT02081755
- Acronym / sponsor ID
- 013-307
- Conditions
- Carcinoma, Hepatocellular
- Keywords
- Immunosuppressive Agents, Liver Transplantation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 336 participants (estimated)
- Lead sponsor
- Baylor Research InstituteUniversity, hospital or other
- Study start
- Mar 2014 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Mar 2027 (estimated)
- First posted
- 7 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a prospective Phase IV study to determine if the use of Everolimus results in lower liver tumor recurrence and improved patient and graft survival after liver transplant for hepatocellular carcinoma (HCC). The immunosuppressive comparators will be Everolimus and Tacrolimus therapy compared to Tacrolimus and Mycophenolic acid/Mycophenolate Mofetil/Azathioprine. Primary outcomes data is disease free survival (the time from randomization to HCC recurrence or death). Secondary outcomes are rate of recurrence of Hepatitis C, problems related to wound healing, hernia repair within the first 12 months, hepatic arterial thrombosis, renal function, acute cellular rejection, post-transplant diabetes, hypertension, and hyperlipidemia.
Detailed description
The study population will consist of approximately 336 patients (224 Everolimus and Tacrolimus and 112 Tacrolimus and Mycophenolic acid/Mycophenolate Mofetil/Azathioprine). Initial screening criteria will include the presence of hepatocellular carcinoma in patients 18 years or older who are candidates to receive a primary orthotopic liver transplant (from deceased or living donor). Within 7 - 12 days post-transplant, patients will be re-evaluated for eligibility for randomization. The criteria include: pre-transplant imaging that shows HCC disease exceeding Milan criteria; pathology review for tumor burden and/or presence of microvascular invasion; AFP >200IU/mL; pre-transplant ablation or resection with HCC recurrence; progression or new tumors; evaluation to rule out any hepatic vessel complication.
Subjects will remain in study treatment until Month 12 at which time the subject and investigator will determine the preferred immunosuppressive regimen. Subjects will be followed for an additional 24 months for outcome data as described above.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Everolimus and Tacrolimus | Experimental | Drug: Everolimus, Drug: TacrolimusEverolimus Dosing: 1.5 mg BID (3.0 mg/day) Tacrolimus Dosing: 0.05 mg/kg BID |
| Tacrolimus and Myfortic or CellCept or Imuran | Active comparator | Drug: Tacrolimus, Drug: Myfortic, Drug: CellCept, Drug: ImuranMyfortic: 360 mg to 1080 mg BID OR CellCept: 500 mg to 1500 mg BID OR Imuran: 0.5mk/kg to 2mg/kg QD AND Tacrolimus Dosing: 0.05 mg/kg BID |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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: Zortress, AfinitorEverolimus Dosing: 1.5 mg BID (3.0 mg/day) for 12 months | Drug | Everolimus and Tacrolimus |
| TacrolimusAlso: PrografTacrolimus Dosing: 0.05 mg/kg BID for 12 months | Drug | Everolimus and Tacrolimus, Tacrolimus and Myfortic or CellCept or Imuran |
| MyforticAlso: Mycophenolic AcidMyfortic®: 360 mg to 1080 mg BID for 12 months | Drug | Tacrolimus and Myfortic or CellCept or Imuran |
| CellCeptAlso: Mycophenolate MofetilCellCept: 500 mg to 1500 mg BID for 12 months | Drug | Tacrolimus and Myfortic or CellCept or Imuran |
| ImuranAlso: Azathioprine0.5 mg/kg to 2 mg/kg QD for 12 months | Drug | Tacrolimus and Myfortic or CellCept or Imuran |
Primary outcome
Disease free survival (DFS) defined as the time from randomization to the time of tumor recurrence or death, whichever occurs first.
Time frame: Through Month 36
10 secondary outcomes
Tumor recurrence sites
Time frame: Through Month 36
Hepatitis C recurrence rate
Time frame: Through Month 36
Renal function
Time frame: Through Month 36
Acute cellular rejection
Time frame: Through Month 36
Post-transplant diabetes
Time frame: Through Month 36
Hypertension
Time frame: Through Month 36
Hyperlipidemia
Time frame: Through Month 36
Wound healing and associated risk factors
Time frame: Through Month 36
Hernia repair
Time frame: Through Month 36
Hepatic arterial thrombosis
Time frame: Through Month 36
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2026.
- Individual participant dataSharing planned: No
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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.
Goran Klintmalm, MD, PhD principal investigator
Baylor Health Care System
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Everolimus, Tacrolimus and Myfortic in people with Carcinoma, Hepatocellular, run by Baylor Research Institute at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: enrolling by invitation, as of the sponsor's last update on 27 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Disease free survival (DFS) defined as the time from randomization to the time of tumor recurrence or death, whichever occurs first. (time frame: Through Month 36). 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 27 Jan 2026.