Hepatocellular CarcinomaPhase 2SirolimusNCT01374750
Efficacy of Sirolimus In Liver Transplantation for Hepatocellular Carcinoma (HCC)
A Phase 2 study testing Sirolimus and m-TOR inhibitor free in people with Hepatocellular Carcinoma, run by Seoul National University Hospital at 1 site in South Korea.
Trial summary
The purpose of this study is to evaluate the anti-tumor effect of sirolimus-based immunosuppressive regimen in patients following living donor liver transplantation for hepatocellular carcinoma exceeding Milan criteria with respect to recurrence-free survival. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Sirolimus and m-TOR inhibitor free
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteSouth Korea
- Study dates
- May 2010to May 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 yrs and weight ≥ 40 kg.
- Histologically proven HCC exceeding Milan criteria before randomization, regardless of the prior therapy
- Signed and dated written informed consent
- Lack of relevant exclusion criteria
- Women who were of childbearing potential must have had a negative qualitative serum pregnancy test before Investigational agent administration and must have agreed to use a medically acceptable method of contraception during treatment period of the study.
Who cannot join
- Multiple organ recipients
- Deceased donor liver transplant
- Known hypersensitivity to Simulect®, sirolimus, tacrolimus, cyclosporine, or MMF or its derivatives
- Hyperlipidemia refractory to optimal medical management (cholesterol >300 mg/dl; Triglycerides > 350 mg/dl)
- Evidence of significant local or systemic infection at the time of randomization.
- Known HIV-positive patients
Show all 15Show fewer
- Women of child-bearing potential not willing to take contraception
- Patients with non-HCC malignancies within the past 5 years, excluding successfully treated squamous cell carcinoma and basal cell carcinoma of the skin
- Patients with HCC involvement of a major branch(portal vein, hepatic vein, etc.) of any hepatic blood vessel on pathological evaluation c.f. Major branch is defined as the first or the second order branch (e.g. In case of the portal vein, right and left portal vein, right anterior and posterior portal vein, and left medial and lateral portal vein)
- Patients with any evidence of extrahepatic HCC metastasis
- Patients with a psychological, familial, sociologic or geographic condition potentially hampering compliance with the study protocol and follow-up schedule
- Use of any investigational drug or treatment up to 4 weeks before enrolling in the study and during the 24-month treatment period.
- Hepatic artery stenosis or occlusion diagnosed by Doppler
- Patients with severe renal insufficiency at randomization time point (GFR < 40mL/min, Proteinuria > 800mg/24hrs)
- Patients with severe leucopenia and/or thrombocytopenia refractory to medical treatment (ANC < 500/ul,platelet < 30K/ul)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Phase Ⅱ, Trial With Sirolimus-containing Versus mTOR-inhibitor Free Immunosuppression in Patients Undergoing Living Donor Liver Transplantation for Hepatocellular Carcinoma Exceeding Milan Criteria
The purpose of this study is to evaluate the anti-tumor effect of sirolimus-based immunosuppressive regimen in patients following living donor liver transplantation for hepatocellular carcinoma exceeding Milan criteria with respect to recurrence-free survival.
Read the detailed description
The Milan criteria were adopted in most of western countries for deceased donor allocation because they identify a subgroup of candidates with hepatocellular carcinoma (HCC) for whom transplant results are similar to those in patients transplanted for end- stage liver disease without HCC. There is a debate involving expanding the indications beyond the Milan criteria in living donor liver transplantation (LDLT). Some transplant surgeons argue that despite the poorer results, LDLT for advanced HCC may be justified, since donors voluntarily accept the risks of donor hepatectomy to dedicate a graft for HCC patients, who may otherwise have no effective treatment. Especially, in Korea where living donor liver transplantation (LDLT) is commonly performed, the expansion of Milan criteria is inevitable. Sirolimus is a macrolide antibiotic produced by Streptomyces hygroscopic that has demonstrated potent immunosuppressive activity in a number of studies. The efficacy of sirolimus as immunosuppressives has been demonstrated in randomized clinical trials in kidney transplantation. The use of sirolimus in liver transplantation is rapidly increasing from the standpoint of reducing the conventional calcineurin inhibitor toxicity. Sirolimus emerged as an effective alternative for patients with renal insufficiency related to calcineurin inhibitor toxicity. In recent studies, no differences have been observed with respect to rejection or major complications.The use of sirolimus in transplant patients is associated with a dose-dependent increase in serum cholesterol and triglycerides that may require treatment. In recent studies in liver transplant recipients using sirolimus as part of a primary immunosuppressive regimen, the occurrence of acute cellular rejection is relatively low. There is data suggesting that sirolimus is associated with hepatic artery thrombosis. Numerous current studies have shown that sirolimus may have inhibitory effects on the development of cancer. Immunosuppressive agent with antineoplastic activity is inherently attractive in the setting of liver transplantation for HCC. If sirolimus shows some degree of anti-tumor effect in transplant recipients with advanced HCC, the indication of LDLT for advanced HCC can be expanded.Our hypothesis is that sirolimus based-regimen will improve the HCC recurrence free survival. If sirolimus-based protocol shows better recurrence free survival, the indication of LDLT for HCC can be expanded. LDLT can be one of the best treatment modalities for advanced HCC. The patients with advanced HCC can have benefit by liver transplantation.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Sirolimus, m-TOR inhibitor free
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called Rapamune
Sirolimus
m-TOR inhibitor freeDrug
Also called Tacrolimus, Cyclosporine
calcineurin inhibitors
| Study group | Role | What they receive |
|---|---|---|
| m-TOR inhibitor free | Active comparator | Immunosuppressive drug Receives: Drug: m-TOR inhibitor free |
| Sirolimus | Experimental | Immunosuppressive drug Receives: Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate recurrence-free survival
To evaluate the anti-tumor effect of sirolimus-based immunosuppressive regimen in patients following living donor liver transplantation for hepatocellular carcinoma exceeding Milan criteria with respect to recurrence-free survival
Measured: 3 years
Secondary outcomes (3)
To evaluate the survival rate
The recurrence is defined by tumor recurrence in imaging study. The recurrence free survival will be calculated by Kaplan-Meier method.
Measured: 3 years
To evaluate the renal function
Renal function will be evaluated by calculated GFR (Cockcroft-Gault method) at postoperative 6month, 12month, 18month, 24month, 30month, and 36month.
Measured: 3 years
To evaluate the safety with sirolimus
Safety of sirolimus will be evaluated by the comparison of proportion of patients with serious adverse events during the follow-up period between two groups (m-TOR goup vs. m-TOR free group). Other minor side effects will be monitored and compared between two groups as well.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2011 (estimated)
- Study startMay 2010
- Primary completionMay 2016
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Seoul National University HospitalThe 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kwang-Woong Lee, Seoul National University Hospital
- Investigators
- Kwang-woong Lee, Principal investigator, Seoul National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01374750
- Sponsor's protocol ID
- KWLee1004-052-316
- Other IDs
- H-1004-052-316
- Acronym
- Sirolimus
- Status last verified
- May 2016
- First submitted
- 21 Apr 2011
- Last updated
- 1 Jun 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase Ⅱ, Trial With Sirolimus-containing Versus mTOR-inhibitor Free Immunosuppression in Patients Undergoing Living Donor Liver Transplantation for Hepatocellular Carcinoma Exceeding Milan Criteria
- ClinicalTrials.gov ID
- NCT01374750
- Acronym / sponsor ID
- Sirolimus / KWLee1004-052-316
- Conditions
- Hepatocellular Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Seoul National University HospitalUniversity, hospital or other
- Study start
- May 2010
- Primary completion
- May 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 16 Jun 2011 (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.
The purpose of this study is to evaluate the anti-tumor effect of sirolimus-based immunosuppressive regimen in patients following living donor liver transplantation for hepatocellular carcinoma exceeding Milan criteria with respect to recurrence-free survival.
Detailed description
The Milan criteria were adopted in most of western countries for deceased donor allocation because they identify a subgroup of candidates with hepatocellular carcinoma (HCC) for whom transplant results are similar to those in patients transplanted for end- stage liver disease without HCC. There is a debate involving expanding the indications beyond the Milan criteria in living donor liver transplantation (LDLT). Some transplant surgeons argue that despite the poorer results, LDLT for advanced HCC may be justified, since donors voluntarily accept the risks of donor hepatectomy to dedicate a graft for HCC patients, who may otherwise have no effective treatment. Especially, in Korea where living donor liver transplantation (LDLT) is commonly performed, the expansion of Milan criteria is inevitable. Sirolimus is a macrolide antibiotic produced by Streptomyces hygroscopic that has demonstrated potent immunosuppressive activity in a number of studies. The efficacy of sirolimus as immunosuppressives has been demonstrated in randomized clinical trials in kidney transplantation. The use of sirolimus in liver transplantation is rapidly increasing from the standpoint of reducing the conventional calcineurin inhibitor toxicity. Sirolimus emerged as an effective alternative for patients with renal insufficiency related to calcineurin inhibitor toxicity. In recent studies, no differences have been observed with respect to rejection or major complications.The use of sirolimus in transplant patients is associated with a dose-dependent increase in serum cholesterol and triglycerides that may require treatment. In recent studies in liver transplant recipients using sirolimus as part of a primary immunosuppressive regimen, the occurrence of acute cellular rejection is relatively low. There is data suggesting that sirolimus is associated with hepatic artery thrombosis. Numerous current studies have shown that sirolimus may have inhibitory effects on the development of cancer. Immunosuppressive agent with antineoplastic activity is inherently attractive in the setting of liver transplantation for HCC. If sirolimus shows some degree of anti-tumor effect in transplant recipients with advanced HCC, the indication of LDLT for advanced HCC can be expanded.Our hypothesis is that sirolimus based-regimen will improve the HCC recurrence free survival. If sirolimus-based protocol shows better recurrence free survival, the indication of LDLT for HCC can be expanded. LDLT can be one of the best treatment modalities for advanced HCC. The patients with advanced HCC can have benefit by liver transplantation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| m-TOR inhibitor free | Active comparator | Drug: m-TOR inhibitor freeImmunosuppressive drug |
| Sirolimus | Experimental | Drug: SirolimusImmunosuppressive drug |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age ≥ 18 yrs and weight ≥ 40 kg.
- Histologically proven HCC exceeding Milan criteria before randomization, regardless of the prior therapy
- Signed and dated written informed consent
- Lack of relevant exclusion criteria
- Women who were of childbearing potential must have had a negative qualitative serum pregnancy test before Investigational agent administration and must have agreed to use a medically acceptable method of contraception during treatment period of the study.
Key exclusion criteria (15 listed)
- Multiple organ recipients
- Deceased donor liver transplant
- Known hypersensitivity to Simulect®, sirolimus, tacrolimus, cyclosporine, or MMF or its derivatives
- Hyperlipidemia refractory to optimal medical management (cholesterol >300 mg/dl; Triglycerides > 350 mg/dl)
- Evidence of significant local or systemic infection at the time of randomization.
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 |
|---|---|---|
| SirolimusAlso: RapamuneSirolimus | Drug | Sirolimus |
| m-TOR inhibitor freeAlso: Tacrolimus, Cyclosporinecalcineurin inhibitors | Drug | m-TOR inhibitor free |
Primary outcome
To evaluate recurrence-free survival
Time frame: 3 years
To evaluate the anti-tumor effect of sirolimus-based immunosuppressive regimen in patients following living donor liver transplantation for hepatocellular carcinoma exceeding Milan criteria with respect to recurrence-free survival
3 secondary outcomes
To evaluate the survival rate
Time frame: 3 years
To evaluate the renal function
Time frame: 3 years
To evaluate the safety with sirolimus
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2016.
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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.
Kwang-woong Lee principal investigator
Seoul National University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sirolimus and m-TOR inhibitor free in people with Hepatocellular Carcinoma, run by Seoul National University Hospital at 1 site in South Korea.
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 5 inclusion and 15 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: finished, as of the sponsor's last update on 1 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. 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 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To evaluate recurrence-free survival (time frame: 3 years). 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 1 Jun 2016.