Sorafenib and Vorinostat in Treating Patients With Advanced Liver Cancer
A Phase I Study of Sorafenib and Vorinostat in Advanced Hepatocellular Carcinoma
2 other identifiers
interventional
16
1 country
2
Brief Summary
This phase I trial is studying the side effects and best dose of vorinostat when given together with sorafenib tosylate in treating patients with advanced liver cancer. Sorafenib tosylate and vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Aug 2010
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 19, 2010
CompletedFirst Posted
Study publicly available on registry
February 24, 2010
CompletedStudy Start
First participant enrolled
August 10, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 2, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
July 18, 2019
CompletedAugust 20, 2019
August 1, 2019
6.5 years
February 19, 2010
August 16, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Determine the appropriate Doses for the combination of sorafenib tosylate and vorinostat appropriate for phase II study in hepatocellular carcinoma (HCC).
Identify the maximum tolerated dose of the combination regimen of vorinostat and sorafenib to study further for efficacy of treatment for hepatocellular carcinoma
4 weeks
Secondary Outcomes (2)
Adverse events will be characterized in terms of nature, severity, attribution, onset and resolution according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Up to 30 days post-treatment
Anti-tumor effects of the combination of sorafenib tosylate and vorinostat
Up to 6 years
Study Arms (2)
Arm A
EXPERIMENTALSorafenib + Vorinostat. Patients receive sorafenib tosylate PO BID continuously and vorinostat PO QD, for 5 days each week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohort A has only one dose level: sorafenib 400 mg orally twice a day with vorinostat 300 mg orally. Cohort A was modified to include 2 dose levels: Dose level A1 (sorafenib 400 mg orally twice a day and vorinostat 200 mg orally once a day) and dose level A-1 (sorafenib 400 mg orally twice a day with vorinostat 100 mg orally once a day). The starting dose upon reopening after approval of this version will be dose level A-1a. Dose level A1 will only be used if dose level A-1a is not tolerable.
Arm B CLOSED
EXPERIMENTALReduced Dose 200mg Sorafenib + Vorinostat. Patients receive sorafenib tosylate PO BID continuously and vorinostat PO QD, for 5 days each week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohort B has 2 dose levels starting at the second dose level (sorafenib 200 mg orally twice a day with vorinostat 400 mg orally). Cohort B has been closed. Cohort B was intended to evaluate the possibility of dose intensification of vorinostat when patients were unable to tolerate standard dose sorafenib, and required dose-reduced sorafenib. The patients accrued to date in Cohort B were unable to tolerate therapy, and it has been determined that dose intensification of vorinostat is not possible, despite reducing the dose of sorafenib.
Interventions
Given orally
Given orally
Eligibility Criteria
You may qualify if:
- Diagnosis of HCC by biopsy-proven pathologic diagnosis or by clinical criteria as defined below:
- \* Clinical criteria to be met if patient has a history of cirrhosis or chronic hepatitis B infection:
- Imaging abnormalities \> 1 cm in size with classic enhancement by magnetic resonance imaging (MRI) or triple-phase computed tomography (CT) scan
- Alpha-fetoprotein (AFP) of any value
- Performance status Eastern Cooperative Oncology Group (ECOG) =\< 1
- If cirrhosis, Child-Pugh classification A or B
- Total bilirubin =\< 3.0 mg/dL
- Creatinine =\< 1.5 x upper limit of normal for the laboratory
- International normalized ratio (INR) =\< 1.7 (if not due to anticoagulants)
- Absolute neutrophil count (ANC) \>= 1,500/mm\^3
- Platelets \>= 80,000/mm\^3
- Hemoglobin (Hgb) \>= 8.5 g/dL (transfusion or erythropoietin-like substances not permitted prior to baseline evaluation)
- Any prior therapies such as surgery, chemoembolization, radiofrequency ablation, and alcohol injection are allowed as long as toxicity from such prior therapy is =\< grade 1
- Prior sorafenib is allowed as long as toxicity from ongoing is ≤ grade 2 and prior intolerance of 400 mg sorafenib PO daily is felt amenable, by the principal investigator, to supportive care measures or dose modifications.
- Measurable or evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria version (v) 1.1 mRECIST or elevated AFP
- +3 more criteria
You may not qualify if:
- Candidate for curative therapy including surgical resection or orthotopic liver transplantation
- Known central nervous system metastasis
- Any investigational agent within 4 weeks of first dose of study treatment
- Known intolerance of vorinostat
- Unable to swallow medication
- Unable to swallow medication; suspected malabsorption
- Active alcohol abuse
- Contraindication to antiangiogenic agents, including:
- Pulmonary hemorrhage/bleeding event \>= grade 2 within 4 weeks of first dose of study drug
- Any other hemorrhage/bleeding event \>= grade 3 within 4 weeks of first dose of study treatment
- Serious non-healing wound, ulcer, or bone fracture
- Major cardiac dysfunction, such as uncontrolled angina, congestive heart failure with New York Heart Association (NYHA) class III or higher, known left ventricular ejection fraction less than 40%
- Systolic blood pressure \> 160 mmHg or diastolic pressure \> 90 mmHg despite optimal medical management
- Significant lung disease (oxygen \[O2\] saturation less than 88% in room air)
- Serious uncontrolled infection; known human immunodeficiency virus (HIV)-seropositivity requiring retroviral therapy, or diagnosis of acquired immune deficiency syndrome (AIDS); diagnosis of chronic hepatitis B or C allowed
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Virginia Commonwealth Universitylead
- Massey Cancer Centercollaborator
Study Sites (2)
Hunter Holmes McGuire VA Medical Center
Richmond, Virginia, 23249, United States
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, 23298, United States
Related Publications (1)
Gordon SW, McGuire WP 3rd, Shafer DA, Sterling RK, Lee HM, Matherly SC, Roberts JD, Bose P, Tombes MB, Shrader EE, Ryan AA, Kmieciak M, Nguyen T, Deng X, Bandyopadhyay D, Dent P, Poklepovic AS. Phase I Study of Sorafenib and Vorinostat in Advanced Hepatocellular Carcinoma. Am J Clin Oncol. 2019 Aug;42(8):649-654. doi: 10.1097/COC.0000000000000567.
PMID: 31305287RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Andrew S. Poklepovic, MD
Massey Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 19, 2010
First Posted
February 24, 2010
Study Start
August 10, 2010
Primary Completion
February 2, 2017
Study Completion
July 18, 2019
Last Updated
August 20, 2019
Record last verified: 2019-08