Sorafenib and Vorinostat in Treating Patients With Advanced Liver Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Virginia Commonwealth University
Sponsor:
Collaborator:
Massey Cancer Center
Information provided by (Responsible Party):
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
NCT01075113
First received: February 19, 2010
Last updated: July 7, 2014
Last verified: July 2014

February 19, 2010
July 7, 2014
August 2010
December 2014   (final data collection date for primary outcome measure)
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
Doses for the combination of sorafenib and vorinostat appropriate for phase II study in hepatocellular carcinoma (HCC) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01075113 on ClinicalTrials.gov Archive Site
  • 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.
  • Safety, tolerance, and toxicity of the combination of sorafenib and vorinostat in patients with HCC [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Anti-tumor effects of the combination [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Sorafenib and Vorinostat in Treating Patients With Advanced Liver Cancer
A Phase I Study of Sorafenib and Vorinostat in Advanced Hepatocellular Carcinoma

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.

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 sorafenib tosylate orally (PO) twice daily (BID) continuously and vorinostat PO once daily (QD), for 5 days each week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Liver Cancer
  • Drug: sorafenib tosylate
    Given orally
    Other Names:
    • BAY 43-9006
    • BAY 43-9006 Tosylate Salt
    • BAY 54-9085
    • Nexavar
    • SFN
  • Drug: vorinostat
    Given orally
    Other Names:
    • L-001079038
    • SAHA
    • suberoylanilide hydroxamic acid
    • Zolinza
  • Experimental: Arm A
    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.
    Interventions:
    • Drug: sorafenib tosylate
    • Drug: vorinostat
  • Experimental: Arm B
    Reduced 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.
    Interventions:
    • Drug: sorafenib tosylate
    • Drug: vorinostat
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
40
December 2015
December 2014   (final data collection date for primary outcome measure)

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
  • Total bilirubin =< 3.0 mg/dL
  • Creatinine =< 1.5 x upper institutional limit
  • prothrombin (PT)/international normalized ratio (INR) =< 1.7 (if not due to anticoagulants)
  • absolute neutrophil count (ANC) >= 1.5
  • Platelets >= 70,000
  • 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 sorafenib is allowed, and patients must be on a stable tolerable dose prior to enrollment; if it is known that the patient tolerates standard dose sorafenib (400 mg orally twice daily), then they will enroll in cohort A; if they tolerate reduced dose sorafenib (200 mg orally twice daily), then they will enroll in cohort B; participation in an additional research imaging study is permissible, imaging for this study will be evaluated independently)
  • 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 2 weeks 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
  • 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; serious non-healing wound, ulcer, or bone fracture.
  • Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months. Hepatic portal vein thrombus is not considered an exclusion criterion, as this is a common finding in patients with advanced liver cancer and progressive disease. This does not confer increased risk for deep venous thrombosis, and is not treated with anticoagulation.
  • 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 human immunodeficiency virus (HIV)-seropositivity requiring retroviral therapy, or diagnosis of acquired immune deficiency syndrome (AIDS); diagnosis of chronic hepatitis B or C allowed
  • Other condition(s) that in the opinion of the investigator might compromise the objectives of the study
Both
18 Years and older
No
Contact: Andrew S. Poklepovic, MD 804-628-2321 apoklepovic@vcu.edu
Contact: Mary B Tombes, NP 804-628-1357 masseyhiit@vcu.edu
United States
 
NCT01075113
MCC-12122, NCI-2010-00185
Yes
Virginia Commonwealth University
Virginia Commonwealth University
Massey Cancer Center
Principal Investigator: Andrew S. Poklepovic, MD Virginia Commonwealth University
Virginia Commonwealth University
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP