Hepatocellular CarcinomaPhase 4NCT01203787
Sorafenib Dose Ramp-Up in Hepatocellular Carcinoma (HCC)
A Phase 4 study testing Sorafenib Standard Dosing Regimen and Sorafenib Ramp-Up Regimen in people with Hepatocellular Carcinoma, run by University of Florida at 9 sites in United States.
Trial summary
Open-label study to evaluate the safety and tolerability of Sorafenib dose ramp-up (starting at a lower dose and then gradually increasing the dose) versus standard Sorafenib dosing in subjects with unresectable and/or metastatic hepatocellular carcinoma. Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Sorafenib Standard Dosing Regimen and Sorafenib Ramp-Up Regimen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 9 sitesUnited States
- Study dates
- Dec 2010to Mar 2014
- Phase
- Phase 4
- 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 20 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HCC must be unresectable and/or metastatic
- CPT score <9 at the time of screening (that is all Child A and Child B with a score of 7 or 8)
- Age 20-75 years
- Signed informed consent
- EGD for variceal screening performed as per standard of care prophylaxis with non-selective beta-blockers or ligation
- ECOG Performance Status ≤ 2.
Show all 18Show fewer
- Adequate bone marrow, liver and renal function as assessed by the following:
- Hemoglobin > 8.5 g/dl
- Absolute neutrophil count (ANC) > 1,500/mm3
- Platelet count > 50,000/mm3
- Total bilirubin < 3 mg/dl
- ALT and AST ( < 5 x ULN)
- Creatinine < 1.5 times ULN
- Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
- Women of childbearing potential and non-surgically sterile 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.
- INR< 2.3. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
- Life expectancy of at least 24 weeks
Who cannot join
- Absence of informed consent
- Child-Pugh score >9
- ECOG PS >2
- Active alcohol dependence per PI discretion
- History of organ or bone marrow transplant
- Plans to relocate from the study center within the period of the trial
Show all 25Show fewer
- Pregnancy or breastfeeding
- Contraindications to sorafenib
- Cardiac disease: Congestive heart failure > class II 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.
- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
- Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
- Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
- Known human immunodeficiency virus (HIV) infection
- Active clinically serious infection > CTCAE Grade 2.
- Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
- Bleeding
- Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug.
- Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug.
- Evidence or history of bleeding diathesis or coagulopathy
- Serious non-healing wound, ulcer, or bone fracture.
- Major surgery, open biopsy or significant traumatic injury within 4 weeks prior to 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.
- Any malabsorption problem.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Henry Ford Health System
Detroit, Michigan, 48202
University of Florida Hepatology
Gainesville, Florida, 32610-0277
University of Texas Health Science Center Houston
Houston, Texas, 77030
Mayo Clinic
Jacksonville, Florida, 32224
Loyola University Medical Center
Maywood, Illinois, 60153
Florida Hospital Transplant Center
Orlando, Florida, 32804
Drexel University College of Medicine
Philadelphia, Pennsylvania, 19107
Brooke Army Medical Center
San Antonio, Texas, 78234
Tampa General Hospital
Tampa, Florida, 33606
About this study
Official title: Multicenter, Randomized Pilot Study of the Effect of Sorafenib Dosing Schedule on Tolerability and Drug Delivery
Open-label study to evaluate the safety and tolerability of Sorafenib dose ramp-up (starting at a lower dose and then gradually increasing the dose) versus standard Sorafenib dosing in subjects with unresectable and/or metastatic hepatocellular carcinoma.
Read the detailed description
This is an open-label study that investigates the impact of a dose ramp-up strategy for sorafenib in patients with HCC. Clinical trial and post-marketing data suggest that sorafenib dose reductions and discontinuations due to adverse events are common and limit the drug's effectiveness. It is our hypothesis that a dose escalation strategy for sorafenib will improve the tolerability and allow a greater percentage of patients to remain on drug. The primary end-point of the study is the total accumulated and median daily dose of sorafenib delivered at month 2 and 4.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Sorafenib Standard Dosing Regimen, Sorafenib Ramp-Up Regimen
- Keywords
- Hepatocellular Carcinoma, HCC, Liver Cancer
- Medical subject headings
- Carcinoma, Hepatocellular, Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sorafenib Standard Dosing RegimenDrug
Also called Nexavar(Bay43-9006)
Sorafenib 400 mg twice daily until wk 24 or end of treatment
Sorafenib Ramp-Up RegimenDrug
Also called Nexavar (Bay43-9006)
200 mg daily, Day 0-Day 13 200 mg twice daily, Day 14-Day 20 600 mg daily, Day 21-Day 27 400 mg twice daily, Day 28 until end of treatment400 mg twice daily
| Study group | Role | What they receive |
|---|---|---|
| Sorafenib Standard Dosing Regimen | Active comparator | Sorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24 Receives: Drug: Sorafenib Ramp-Up Regimen |
| Sorafenib Ramp-Up Regimen | Experimental | 200 mg daily from Day 0-Day 13 200 mg twice daily from Day 14-Day 20 600 mg daily from Day 21-Day 27 400 mg twice daily beginning Day 28 until end of treatment or Week 24 Receives: Drug: Sorafenib Standard Dosing Regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total (Cumulative) Dose Delivery of Sorafenib
This outcome measure table shows the median cumulative dose delivered to the subjects randomized to the standard dosing regimen (N=63) and ramp-up regimen (N=57) at 4 months of treatment.
Measured: 4 months-1/12/2010-1/27/14
Cumulative Dose of Sorafenib
Table below shows mean cumulative dose of sorafenib for each of the dosing regimens.
Measured: 11/22/2010-1/27/14
Secondary outcomes (5)
Safety and Efficacy of Sorafenib Dosing Regimens
Safety of Sorafenib was assessed by the frequency and severity of adverse events according to NCI-CTCAE grading
Measured: Baseline-End of Treatment (11/22/2010-3/10/2014)
Safety of Dosing Regimens as Assessed by the Frequency and Severity of Adverse Events According to National Cancer Institute- CTCAE
The total number of CTCAE (Common Terminology Criteria) grade 4 adverse events was collected for each dosing regimen beginning at baseline until Week 24/Early Termination Visit.
Measured: 11/22/2010-3/10/2014
Frequency and Severity of Adverse Events According to National Cancer Institute- CTCAE
The total number of CTCAE (Common Terminology Criteria) grade 5 adverse events was collected for each dosing regimen beginning at baseline through 6 months of treatment.
Measured: 11/22/2010-3/10/2014
Number of Subjects With Dose Interruptions
Measured: Baseline-End of Treatment (11/22/2010-3/10/2014)
Number of Subjects With Dose Reductions
Measured: 11/22/2010-3/10/2014
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2010 (estimated)
- Study startDec 2010
- Primary completionJan 2014
- Study completionMar 2014
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 University of FloridaThe 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
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David R Nelson, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01203787
- Sponsor's protocol ID
- ONC-2010-19
- Status last verified
- Feb 2015
- First submitted
- 10 Sep 2010
- Last updated
- 5 Mar 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter, Randomized Pilot Study of the Effect of Sorafenib Dosing Schedule on Tolerability and Drug Delivery
- ClinicalTrials.gov ID
- NCT01203787
- Acronym / sponsor ID
- ONC-2010-19
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Hepatocellular Carcinoma, HCC, Liver Cancer
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Study start
- Dec 2010
- Primary completion
- Jan 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 16 Sep 2010 (estimated)
- Results
- Posted 11 Feb 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Open-label study to evaluate the safety and tolerability of Sorafenib dose ramp-up (starting at a lower dose and then gradually increasing the dose) versus standard Sorafenib dosing in subjects with unresectable and/or metastatic hepatocellular carcinoma.
Detailed description
This is an open-label study that investigates the impact of a dose ramp-up strategy for sorafenib in patients with HCC. Clinical trial and post-marketing data suggest that sorafenib dose reductions and discontinuations due to adverse events are common and limit the drug's effectiveness. It is our hypothesis that a dose escalation strategy for sorafenib will improve the tolerability and allow a greater percentage of patients to remain on drug. The primary end-point of the study is the total accumulated and median daily dose of sorafenib delivered at month 2 and 4.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sorafenib Standard Dosing Regimen | Active comparator | Drug: Sorafenib Ramp-Up RegimenSorafenib 400 mg (2 tablets of 200 mg) twice daily until end of treatment or week 24 |
| Sorafenib Ramp-Up Regimen | Experimental | Drug: Sorafenib Standard Dosing Regimen200 mg daily from Day 0-Day 13 200 mg twice daily from Day 14-Day 20 600 mg daily from Day 21-Day 27 400 mg twice daily beginning Day 28 until end of treatment or Week 24 |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- HCC must be unresectable and/or metastatic
- CPT score <9 at the time of screening (that is all Child A and Child B with a score of 7 or 8)
- Age 20-75 years
- Signed informed consent
- EGD for variceal screening performed as per standard of care prophylaxis with non-selective beta-blockers or ligation
Key exclusion criteria (25 listed)
- Absence of informed consent
- Child-Pugh score >9
- ECOG PS >2
- Active alcohol dependence per PI discretion
- History of organ or bone marrow transplant
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 |
|---|---|---|
| Sorafenib Standard Dosing RegimenAlso: Nexavar(Bay43-9006)Sorafenib 400 mg twice daily until wk 24 or end of treatment | Drug | Sorafenib Ramp-Up Regimen |
| Sorafenib Ramp-Up RegimenAlso: Nexavar (Bay43-9006)200 mg daily, Day 0-Day 13 200 mg twice daily, Day 14-Day 20 600 mg daily, Day 21-Day 27 400 mg twice daily, Day 28 until end of treatment400 mg twice daily | Drug | Sorafenib Standard Dosing Regimen |
Primary outcome
Total (Cumulative) Dose Delivery of Sorafenib
Time frame: 4 months-1/12/2010-1/27/14
This outcome measure table shows the median cumulative dose delivered to the subjects randomized to the standard dosing regimen (N=63) and ramp-up regimen (N=57) at 4 months of treatment.
Cumulative Dose of Sorafenib
Time frame: 11/22/2010-1/27/14
Table below shows mean cumulative dose of sorafenib for each of the dosing regimens.
5 secondary outcomes
Safety and Efficacy of Sorafenib Dosing Regimens
Time frame: Baseline-End of Treatment (11/22/2010-3/10/2014)
Safety of Dosing Regimens as Assessed by the Frequency and Severity of Adverse Events According to National Cancer Institute- CTCAE
Time frame: 11/22/2010-3/10/2014
Frequency and Severity of Adverse Events According to National Cancer Institute- CTCAE
Time frame: 11/22/2010-3/10/2014
Number of Subjects With Dose Interruptions
Time frame: Baseline-End of Treatment (11/22/2010-3/10/2014)
Number of Subjects With Dose Reductions
Time frame: 11/22/2010-3/10/2014
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Hepatocellular Carcinoma
RecruitingObservational study
Real-world Evaluation of the HistoSonics Edison System for Treatment of Liver Tumors Across Multidisciplinary Users (BOOMBOX: Master Study)
Liver Neoplasms, Primary Liver Cancer
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingObservational study
A Study to Evaluate Patient-Reported Satisfaction, Effectiveness, and Safety of Atezolizumab in Participants Treated in Routine Clinical Practice
Lung Cancer, Hepatocellular Carcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
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.
David R Nelson, MD principal investigator
University of Florida
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 Sorafenib Standard Dosing Regimen and Sorafenib Ramp-Up Regimen in people with Hepatocellular Carcinoma, run by University of Florida 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?
The sponsor lists 18 inclusion and 25 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 5 Mar 2015. 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?
Yes. Results are posted in the registry (first posted 11 Feb 2015). 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?
Total (Cumulative) Dose Delivery of Sorafenib (time frame: 4 months-1/12/2010-1/27/14). The study lists 2 primary outcomes in all. 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 5 Mar 2015.