Carcinoma, HepatocellularEarly Phase 1NCT01337492
Pilot Study Sorafenib as Bridge to Orthotopic Liver Transplantation (OLT)
A Early Phase 1 study testing Nexavar in people with Carcinoma, Hepatocellular, run by Case Comprehensive Cancer Center at 1 site in United States.
Trial summary
Patients with either histological confirmation or clinical diagnosis who are candidate for orthotopic liver transplant(OLT) will receive Sorafenib 400mg 2 x day (BID) as a neoadjuvant (bridging) treatment until transplant. 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?
- Nexavar
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2010to Jan 2012
- Phase
- Early Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18 years old
- Confirmation of diagnosis of Hepato Cellular Carcinoma (HCC) and within Milan criteria awaiting liver transplant or going through evaluation for Liver Transplant.
- Either histological confirmation or clinical diagnosis by American Association for the Study of Liver Diseases(AASLD) criteria (see Appendix 1) in cirrhotic subjects is required. For subjects without cirrhosis histological confirmation is mandatory.
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
- Child Pugh A or B (Total point of 7 will be allowed See appendix for scoring system). (ONLY 4 patients with Child Pugh B7 will be allowed.)
- Adequate bone marrow, liver and renal function as assessed by the following:
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- Hemoglobin > 8.5 g/dl
- Absolute neutrophil count (ANC) > 1,500/mm3
- Platelet count > 60,000/mm3
- Total bilirubin < 1.5 times Upper Limits of Normal (ULN)
- ALT and AST < 2.5 times the Upper Limits of Normal (ULN) ( < 5 x ULN for patients with liver involvement)
- Creatinine < 1.5 times Upper Limits of Normal (ULN)
- Women of childbearing potential must have 2 negative serum pregnancy test performed. The first test within 7-10 days prior to the start of treatment. The second test within 24 hours prior to start of treatment.
- Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men should use adequate birth control for at least three months after the last administration of sorafenib.
- Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.
Who cannot join
- Cardiac disease: Congestive heart failure > class II New York Heart Association (NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
- Prior use of sorafenib
- Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
- Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
- Known human immunodeficiency virus (HIV) infection.
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- Active clinically serious infection > CTCAE Grade 2 except for Except Hepatitis B(HBV) or Hepatitis C (HCV)
- Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
- Serious non-healing wound, ulcer, or bone fracture.
- Evidence or history of bleeding diathesis
- Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
- Use of St. John's Wort or rifampin (rifampicin).
- Known or suspected allergy to sorafenib or any agent given in the course of this trial.
- Any condition that impairs patient's ability to swallow whole pills.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, 44195
About this study
Official title: Pilot Study: Safety and Feasibility of Using Sorafenib as Neoadjuvant Treatment Prior to Orthotopic Liver Transplantation (OLT) in Patients With Hepatocellular Carcinoma
Patients with either histological confirmation or clinical diagnosis who are candidate for orthotopic liver transplant(OLT) will receive Sorafenib 400mg 2 x day (BID) as a neoadjuvant (bridging) treatment until transplant. If patient progresses or falls outside of the Milan criteria on sorafenib patient can be treated per physician's discretion using local therapy. Patient will be followed until 30 days after the orthotopic liver transplant (OLT).
Read the detailed description
Primary objective:
- To evaluate safety (including possible surgical complication) and feasibility of using sorafenib as neo-adjuvant (bridging therapy) prior to orthotopic liver transplant(OLT).
The primary goal of this pilot study is to assess the safety and feasibility of treating HCC patients with sorafenib prior to OLT, as determined by the number of patients experiencing grade 4 hemorrhaging or bleeding post-operatively.
To achieve these goals a 2-stage accrual design will be used with a maximum accrual goal of 10 patients. Initially 5 patients will be entered on-study. If more than one patient experiences grade 4 hemorrhaging/bleeding following OLT the trial will be closed and sorafenib will not be considered safe and/or feasible. If no patient experiences this event 5 additional patients will be enrolled. At the end of the study sorafenib will be considered safe and feasible in this setting if no patient experience grade 4 hemorrhaging/bleeding following transplant. With this design, and assuming at least 3 of the 5 patients in each cohort undergo OLT, the likelihood of stopping early is <.04 if the underlying risk hemorrhages/bleeding are low (<5% each) whereas there is a >.42 chance of early termination if the risks are substantial (e.g. >.20 likelihood of dose limiting toxicity and >.30 likelihood of >grade 4 hemorrhages/bleeding). Overall the likelihood of accepting or not accepting sorafenib as safe and feasible are >.84, and <.16, respectively under these conditions.
Secondary objectives:
- Drop out rate
- Time to progression prior to orthotopic liver transplant (OLT)
- Waiting time.
- Conditions
- Carcinoma, Hepatocellular
- Being tested
- Nexavar
- Keywords
- Hepatocellular Carcinoma, Orthotopic Liver Transplant
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NexavarDrug
400 mg of Sorafenib
| Study group | Role | What they receive |
|---|---|---|
| Sorafenib | Experimental | Not described Receives: Drug: Nexavar |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events associated with technical aspects of the operation
To assess the safety and feasibility of treating HCC patients with sorafenib prior to OLT, as determined by the number of patients experiencing grade 4 hemorrhaging needing blood trnasfusion, thrombosis of vascular graft structures, stenosis of vascular anastomosis or biliary leaks or anastomotic biliary stenosis.
Measured: post-transplant
Secondary outcomes (3)
Time to progression prior to OLT
A measure of time after being put on transplant list until the disease is beyond Milan's criteria prior to OLT.
Measured: 10 - 12 months
Drop Out Rate
This is the rate of subjects who were eligible for liver transplant but drop out secondary to disease progression while awaiting donor organ.
Measured: 10-12 months
Waiting Time
This is number of months from the time patient get listed on the transplant list to the time patient under goes actual liver transplant.
Measured: 10-12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2011 (estimated)
- Study startSep 2010
- Primary completionMay 2011
- Study completionJan 2012
Why it stopped: slow accrual
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 Case Comprehensive Cancer CenterThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer, Onyx Therapeutics, Inc.
- Responsible party
- Sponsor
- Investigators
- Robert Pelley, MD, Principal investigator, CCF Taussig Cancer Solid Tumor Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01337492
- Sponsor's protocol ID
- CASE2209
- Status last verified
- Mar 2012
- First submitted
- 19 Jan 2011
- Last updated
- 21 Mar 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study: Safety and Feasibility of Using Sorafenib as Neoadjuvant Treatment Prior to Orthotopic Liver Transplantation (OLT) in Patients With Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT01337492
- Acronym / sponsor ID
- CASE2209
- Conditions
- Carcinoma, Hepatocellular
- Keywords
- Hepatocellular Carcinoma, Orthotopic Liver Transplant
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow accrual
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- Bayer, Onyx Therapeutics, Inc.
- Study start
- Sep 2010
- Primary completion
- May 2011 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 19 Apr 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.
Patients with either histological confirmation or clinical diagnosis who are candidate for orthotopic liver transplant(OLT) will receive Sorafenib 400mg 2 x day (BID) as a neoadjuvant (bridging) treatment until transplant. If patient progresses or falls outside of the Milan criteria on sorafenib patient can be treated per physician's discretion using local therapy. Patient will be followed until 30 days after the orthotopic liver transplant (OLT).
Detailed description
Primary objective:
- To evaluate safety (including possible surgical complication) and feasibility of using sorafenib as neo-adjuvant (bridging therapy) prior to orthotopic liver transplant(OLT).
The primary goal of this pilot study is to assess the safety and feasibility of treating HCC patients with sorafenib prior to OLT, as determined by the number of patients experiencing grade 4 hemorrhaging or bleeding post-operatively.
To achieve these goals a 2-stage accrual design will be used with a maximum accrual goal of 10 patients. Initially 5 patients will be entered on-study. If more than one patient experiences grade 4 hemorrhaging/bleeding following OLT the trial will be closed and sorafenib will not be considered safe and/or feasible. If no patient experiences this event 5 additional patients will be enrolled. At the end of the study sorafenib will be considered safe and feasible in this setting if no patient experience grade 4 hemorrhaging/bleeding following transplant. With this design, and assuming at least 3 of the 5 patients in each cohort undergo OLT, the likelihood of stopping early is <.04 if the underlying risk hemorrhages/bleeding are low (<5% each) whereas there is a >.42 chance of early termination if the risks are substantial (e.g. >.20 likelihood of dose limiting toxicity and >.30 likelihood of >grade 4 hemorrhages/bleeding). Overall the likelihood of accepting or not accepting sorafenib as safe and feasible are >.84, and <.16, respectively under these conditions.
Secondary objectives:
- Drop out rate
- Time to progression prior to orthotopic liver transplant (OLT)
- Waiting time.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sorafenib | Experimental | Drug: Nexavar |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Age > 18 years old
- Confirmation of diagnosis of Hepato Cellular Carcinoma (HCC) and within Milan criteria awaiting liver transplant or going through evaluation for Liver Transplant.
- Either histological confirmation or clinical diagnosis by American Association for the Study of Liver Diseases(AASLD) criteria (see Appendix 1) in cirrhotic subjects is required. For subjects without cirrhosis histological confirmation is mandatory.
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
- Child Pugh A or B (Total point of 7 will be allowed See appendix for scoring system). (ONLY 4 patients with Child Pugh B7 will be allowed.)
Key exclusion criteria (14 listed)
- Cardiac disease: Congestive heart failure > class II New York Heart Association (NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
- Prior use of sorafenib
- Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
- Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
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 |
|---|---|---|
| Nexavar400 mg of Sorafenib | Drug | Sorafenib |
Primary outcome
Adverse events associated with technical aspects of the operation
Time frame: post-transplant
To assess the safety and feasibility of treating HCC patients with sorafenib prior to OLT, as determined by the number of patients experiencing grade 4 hemorrhaging needing blood trnasfusion, thrombosis of vascular graft structures, stenosis of vascular anastomosis or biliary leaks or anastomotic biliary stenosis.
3 secondary outcomes
Time to progression prior to OLT
Time frame: 10 - 12 months
Drop Out Rate
Time frame: 10-12 months
Waiting Time
Time frame: 10-12 months
Results and safety
The study was stopped early (reason given: slow accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2012.
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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.
Robert Pelley, MD principal investigator
CCF Taussig Cancer Solid Tumor Oncology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Nexavar in people with Carcinoma, Hepatocellular, run by Case Comprehensive Cancer Center at 1 site 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?
The sponsor lists 15 inclusion and 14 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 21 Mar 2012. 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 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 was stopped early (reason given: slow accrual). Results are not available in the source record.
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?
Adverse events associated with technical aspects of the operation (time frame: post-transplant). 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 21 Mar 2012; AzTrials last refreshed its copy on 7 Nov 2026.