ClinicalTrials.gov

History of Changes for Study: NCT02081755
Safety and Efficacy of Everolimus Treatment in Liver Transplantation for Liver Cancer
Latest version (submitted July 19, 2022) on ClinicalTrials.gov
  • A study version is represented by a row in the table.
  • Select two study versions to compare. One each from columns A and B.
  • Choose either the "Merged" or "Side-by-Side" comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only applies to the Protocol section of the study.
  • Click "Compare" to do the comparison and show the differences.
  • Select a version's Submitted Date link to see a rendering of the study for that version.
  • The yellow A/B choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed.
  • Hover over the "Recruitment Status" to see how the study's recruitment status changed.
  • Study edits or deletions are displayed in red.
  • Study additions are displayed in green.
Study Record Versions
Version A B Submitted Date Changes
1 March 5, 2014 None (earliest Version on record)
2 January 26, 2015 Study Status and Eligibility
3 July 27, 2015 Study Status
4 February 11, 2016 Contacts/Locations, Study Status and Study Description
5 February 14, 2017 Contacts/Locations, Arms and Interventions, Study Status, IPDSharing, Eligibility, Outcome Measures and Study Description
6 July 11, 2018 Study Status, Arms and Interventions, Contacts/Locations, Study Description and Eligibility
7 October 24, 2019 Recruitment Status, Study Status and Contacts/Locations
8 July 19, 2022 Study Status
Comparison Format:

Scroll up to access the controls

Study NCT02081755
Submitted Date:  March 5, 2014 (v1)

Open or close this module Study Identification
Unique Protocol ID: 013-307
Brief Title: Safety and Efficacy of Everolimus Treatment in Liver Transplantation for Liver Cancer
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
Secondary IDs:
Open or close this module Study Status
Record Verification: March 2014
Overall Status: Recruiting
Study Start: March 2014
Primary Completion: June 2018 [Anticipated]
Study Completion: June 2018 [Anticipated]
First Submitted: March 5, 2014
First Submitted that
Met QC Criteria:
March 5, 2014
First Posted: March 7, 2014 [Estimate]
Last Update Submitted that
Met QC Criteria:
March 5, 2014
Last Update Posted: March 7, 2014 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Baylor Research Institute
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Open or close this module Study Description
Brief 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). The immunosuppressive comparators will be Everolimus and Tacrolimus therapy compared to Tacrolimus and Mycophenolic acid/Mycophenolate Mofetil. 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 (225 Everolimus and Tacrolimus and 111 Tacrolimus and Mycophenolic acid/Mycophenolate Mofetil). Initial screening criteria will include patients 18 years or older who are candidates to receive a primary orthotopic liver transplant (from deceased or living donor). Within 7 - 10 days post-transplant, patients will be re-evaluated for eligibility for randomization. The criteria include the presence of hepatocellular carcinoma in the explant as determined by pathology evaluation, pathology review for tumor burden, presence of microvascular invasion, no evidence of hepatic vessel complications, functioning liver allograft, able to take oral medications and no systemic infection or delayed wound healing.

Subjects will remain in study treatment until Month 24 at which time the subject and investigator will determine the preferred immunosuppressive regimen. Subjects will be followed for an additional 12 months for outcome data as described above.

Open or close this module Conditions
Conditions: Carcinoma, Hepatocellular
Keywords: Immunosuppressive Agents
Liver Transplantation
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 4
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 336 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Everolimus and Tacrolimus
Everolimus Dosing: 1.5 mg BID (3.0 mg/day) Tacrolimus Dosing: 0.05 mg/kg BID
Drug: Everolimus
Everolimus Dosing: 1.5 mg BID (3.0 mg/day) for 24 months
Other Names:
  • Zortress
Drug: Tacrolimus
Tacrolimus Dosing: 0.05 mg/kg BID for 24 months
Other Names:
  • Prograf
Active Comparator: Tacrolimus and Myfortic or CellCept
Myfortic: 360 mg to 1080 mg BID OR CellCept: 500 mg to 1500 mg BID AND Tacrolimus Dosing: 0.05 mg/kg BID
Drug: Tacrolimus
Tacrolimus Dosing: 0.05 mg/kg BID for 24 months
Other Names:
  • Prograf
Drug: Myfortic
Myfortic®: 360 mg to 1080 mg BID for 24 months
Other Names:
  • Mycophenolic Acid
Drug: CellCept
CellCept: 500 mg to 1500 mg BID for 24 months
Other Names:
  • Mycophenolate Mofetil
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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 ]

Secondary Outcome Measures:
1. Tumor recurrence sites
[ Time Frame: Through Month 36 ]

2. Hepatitis C recurrence rate
[ Time Frame: Through Month 36 ]

3. Renal function
[ Time Frame: Through Month 36 ]

4. Acute cellular rejection
[ Time Frame: Through Month 36 ]

5. Post-transplant diabetes
[ Time Frame: Through Month 36 ]

6. Hypertension
[ Time Frame: Through Month 36 ]

7. Hyperlipidemia
[ Time Frame: Through Month 36 ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

Screening

  • Listed as a patient within the top 20 on the wait list at each study site/center
  • 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

Randomization

  • HCC in the explanted liver showing a tumor burden exceeding Milan criteria, and/or poorly differentiated tumors based on histology exam, and/or with microscopic vascular invasion based on pathology reports and/or alpha- fetoprotein (AFP) >200 IU/mL taken at the most recent time point prior to randomization.
  • For patients with a history of any hepatic vessel thrombosis, occlusion, stent placement, or major reconstruction of liver vessels, must have a Doppler ultrasound 1-2 days prior to randomization to rule out any hepatic vessel complication, including hepatic arterial thrombosis (HAT).
  • Patient is able to take oral medications.
  • Pathology findings of viable tumor.
  • Downstaged tumors, if upon explant, meet randomization criteria.
  • Functioning liver allograft at the time of randomization

Exclusion Criteria:

Screening

  • Past or present malignancy within the last 5 years (other than excised basal cell carcinoma and/or HCC satisfying the Milan criteria).
  • 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.
  • 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.

Randomization

  • Complete necrosis of HCC nodules on explant.
  • 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.
  • Incomplete wound healing at the surgical site including infections, dehiscence or a condition that requires the wound to remain open.
  • 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.
  • Major/reconstructed hepatic vein, portal vein or inferior vena cava at any time prior to randomization.
Open or close this module Contacts/Locations
Central Contact Person: Sharon Primeaux, MS
Email: sharon.primeaux@baylorhealth.edu
Central Contact Backup: Michelle Acker, BSN
Email: michelle.acker@baylorhealth.edu
Study Officials: Goran Klintmalm, MD, PhD
Principal Investigator
Baylor Health Care System
Locations: United States, Texas
Baylor University Medical Center
[Recruiting]
Dallas, Texas, United States, 75246
Contact:Contact: Sharon Primeaux, MS 214-818-7876 sharon.primeaux@baylorhealth.edu
Contact:Principal Investigator: Goran Klintmalm, MD, PhD
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:

Scroll up to access the controls Scroll to the Study top

U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services