Sorafenib and Vorinostat in Treating Patients With Advanced Liver Cancer
This study is currently recruiting participants.
Verified April 2013 by Virginia Commonwealth University
Sponsor:
Virginia Commonwealth University
Collaborator:
Massey Cancer Center
Information provided by (Responsible Party):
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
NCT01075113
First received: February 19, 2010
Last updated: April 26, 2013
Last verified: April 2013
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Purpose
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. Giving sorafenib tosylate together with vorinostat may kill more tumor cells.
| Condition | Intervention | Phase |
|---|---|---|
|
Liver Cancer |
Drug: sorafenib tosylate Drug: vorinostat |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase I Study of Sorafenib and Vorinostat in Advanced Hepatocellular Carcinoma |
Resource links provided by NLM:
Further study details as provided by Virginia Commonwealth University:
Primary Outcome Measures:
- Determine the appropriate doses of vorinostat and sorafenib when given in combination to patients with hepatocellular carcinoma [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]Identify the maximum tolerated dose of the combination regimen of vorinostat and sorafenib to study further for efficacy of treatment for hepatocellular carcinoma
Secondary Outcome Measures:
- Define maximum tolerated dose of the combination of vorinostat and sorafenib in patients treated for hepatocellular carcinoma in patients with HCC [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]Observe toxicities experienced by patients treated in cohorts of escalating doses of the drug combination.
- Anti-tumor effects of the combination [ Time Frame: 2 years ] [ Designated as safety issue: No ]Observe whether treatment with vorinostat and sorafenib affects the growth of the hepatocellular tumor.
| Estimated Enrollment: | 20 |
| Study Start Date: | August 2010 |
| Estimated Study Completion Date: | December 2015 |
| Estimated Primary Completion Date: | December 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm I
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.
|
Drug: sorafenib tosylate
Given orally
Other Names:
Drug: vorinostat
Given orally
Other Names:
|
Detailed Description:
Primary Objectives:
I. To determine doses for the combination of vorinostat with standard dose sorafenib (400 mg twice daily) and reduced dose sorafenib (200 mg twice daily appropriate for phase II study in HCC.
Secondary Objectives:
I. To evaluate the safety, tolerance, and toxicity of the combination of sorafenib and vorinostat in patients with HCC.
II. To observe antitumor effects of the combination. III. To evaluate the feasibility of circulating tumor cell analysis for tumor cell enumeration, and target protein expression on HCC tumor cells.
Outline: This is a dose-escalation study of vorinostat. Patients receive oral sorafenib tosylate twice daily for 3 weeks and oral vorinostat once daily, 5 days a week, for 3 weeks. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion
- Diagnosis of hepatocellular carcinoma (HCC): The diagnosis of HCC may be based upon pathological or clinical criteria (Clinical diagnosis requires a history of cirrhosis, chronic hepatitis B infection, or non-alcoholic hepatosteatosis (NASH) and, for imaging abnormalities 1 to 2 cm in diameter, classic enhancement by at least two of three imaging techniques (computed tomography, Magnetic resonance imaging, Ultrasound), or, for imaging abnormalities > 2cm, classic enhancement by at least one imaging technique and an alpha-fetoprotein (AFP) > 200 ng/mL
- Performance status Eastern Cooperative Oncology Group (ECOG) equal or less than 2
- If cirrhosis, Child-Pugh classification A or B
- Aspartate aminotransferase (AST), alanine transaminase (ALT) =< 5 x upper institutional limit
- alkaline phosphatase (ALP) =< 3 x upper institutional limit
- Total bilirubin =< 3.0 mg/dL
- Creatinine =< 1.5 x upper institutional limit
- prothrombin (PT)/international normalized ratio (INR) =< 1.5 (if not due to anticoagulants)
- white blood cell (WBC) count >= 3.0
- absolute neutrophil count (ANC) >= 1.5
- Platelets >= 60,000
- hemoglobin (Hgb) >= 8.5 (transfusion or erythropoietin-like substances not permitted)
- Any prior therapies such as surgery, chemoembolization, radiofrequency ablation, and alcohol injection are allowed as long as toxicity from prior therapy is =< grade 1 (Prior and/or concurrent sorafenib is allowed if it is known that the patient tolerates standard dose sorafenib, that is, sorafenib 400 mg by mouth twice daily)
- Measurable or evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria or elevated AFP
- Ability to understand and willingness to sign a written informed consent (A signed informed consent must be obtained prior to any study specific procedures)
- Women of childbearing potential must have a negative pregnancy test performed within 7 days prior to the start of treatment (Women of childbearing potential and men must agree to use a medically accepted form of birth control for the duration of study participation; Men must agree to use a medically accepted form of birth control for 4 months following completion of study treatment)
Exclusion
- Candidate for surgical resection, orthotopic liver transplantation, or loco-regional therapy such as radio-frequency ablation or chemoembolization
- Known central nervous system metastasis
- Any investigational agent within 4 weeks or 5 half-times, whichever is longer, of first dose of study treatment
- Known or presumed intolerance of sorafenib or vorinostat
- Unable to swallow medication
- Suspected malabsorption
- Active illicit substance or 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.
- Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months
- 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 saturation less than 88% in room air) - Serious uncontrolled infection (Known HIV-seropositivity regardless of treatment status)
- Serious non-healing wound, ulcer, or bone fracture
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01075113
Contacts
| Contact: Andrew S. Poklepovic, MD | 804-628-2321 | apoklepovic@vcu.edu |
| Contact: Maria Quigley, RN | 804-628-3836 | mquigley@vcu.edu |
Locations
| United States, Virginia | |
| Virginia Commonwealth University | Recruiting |
| Richmond, Virginia, United States, 23298 | |
| Contact: Andrew Poklepovic, MD 804-628-2321 apoklepovic@vcu.edu | |
| Contact: Maria Quigley, RN 804-628-3836 mquigley@vcu.edu | |
| Principal Investigator: Andrew Poklepovic, MD | |
| Hunter Holmes McGuire VA Medical Center | Recruiting |
| Richmond, Virginia, United States, 23249 | |
| Contact: Rosemarie Mannino, MD 804-675-5000 ext 4310 rosemarie.mannino@va.gov | |
| Principal Investigator: Rosemarie Mannino, MD | |
Sponsors and Collaborators
Virginia Commonwealth University
Massey Cancer Center
Investigators
| Principal Investigator: | Andrew S. Poklepovic, MD | Virginia Commonwealth University |
More Information
No publications provided
| Responsible Party: | Virginia Commonwealth University |
| ClinicalTrials.gov Identifier: | NCT01075113 History of Changes |
| Other Study ID Numbers: | MCC-12122, NCI-2010-00185 |
| Study First Received: | February 19, 2010 |
| Last Updated: | April 26, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Virginia Commonwealth University:
|
adult primary hepatocellular carcinoma advanced adult primary liver cancer recurrent adult primary liver cancer |
Additional relevant MeSH terms:
|
Liver Neoplasms Carcinoma, Hepatocellular Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Liver Diseases Adenocarcinoma Carcinoma Neoplasms, Glandular and Epithelial |
Neoplasms by Histologic Type Vorinostat Sorafenib Histone Deacetylase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Protein Kinase Inhibitors |
ClinicalTrials.gov processed this record on May 22, 2013