A Pilot Study of Sorafenib Examining Biomarkers in Refractory or Relapsed T-Cell Lymphoma Patients

Trial Purpose and Description

Trial Purpose

The drug being studied in this research study is called sorafenib (Nexavar). Sorafenib is a standard therapy approved by the United States Food and Drug Administration (FDA) to treat renal cell (kidney) cancer, and hepatocellular (liver) cancer. It is not approved for use in lymphoma, however, the FDA does permit its use in studies like this one where we look at biomarkers to see what effects this drug has on you and your cancer. Sorafenib is a drug that stops the growth of cancer cells and prevents the formation of new blood vessels that would normally help the cancer survive and spread. The study in which you are now being asked to participate is the first study to examine use of sorafenib in participants with T-cell lymphoma who have been treated with at least one prior therapy but the disease has gotten worse, has not gone away, or came back after treatment with other medicines.

Participation Guidelines

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed T-cell lymphoma including PTCL, AITL, CTCL, ALCL (Alk+, and Alk-), and other transformed T-cell lymphomas.
• Relapsed or refractory to at least one standard chemotherapy regimen. Patients with prior autologous stem cell transplant will be eligible to participate.
• Patients must have discontinued any prior treatment for at least two weeks prior to receiving the first dose of the study drug, sorafenib.
• All prior toxicities from prior treatment must have resolved to grade 1 or less
• Age > 18 years old
• Measureable disease, as defined by the Cheson criteria
• ECOG Performance Status of 0 or 1
• Life expectancy > 12 weeks
• Adequate bone marrow, liver  and renal function as assessed by the following:
  • Hemoglobin > 8.5 g/dl
  • Absolute neutrophil count (ANC) > 1000/mm³
  • Platelet count >75,000/mm³
  • Total bilirubin <1.5 times ULN
  • ALT and AST <2.5 times the ULN ( < 5 x ULN for patients with liver involvement)
  • Creatinine < 2 times ULN
  • INR < 1.5 or a PT/PTT within normal limits.  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.
• Patients with hemoglobin < 8.5g/dL, or ANC 500-1000/mm3, or platelets 50,000-75,000/mm3 (Grade 3), whose cytopenias are due to bone marrow involvement by T-cell lymphoma will also be eligible (see  Section 6: DOSING DELAYS/DOSE MODIFICATIONS).
• Women of childbearing potential must have a negative serum pregnancy test performed within seven days prior to the 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.

Exclusion Criteria

• Prior treatment with sorafenib, or other agents with similar activity, i.e. bevacizumab, imatinib, sunitinib.
• Prior treatment with allogeneic stem cell transplant.
• Patients taking any systemic steroids greater than prednisone 10mg daily or its equivalent.
• 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.
• Known CNS 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.
• Active clinically serious infection > CTCAE Grade 2.
• Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
• 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.
• Serious non-healing wound, ulcer, or bone fracture.
• Evidence or history of bleeding diathesis or coagulopathy
• 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

Sponsor:

Bayer

Yale Cancer Center

Dates:

October 2009

Last Updated:

Study HIC#:

0901004690

Clinicaltrials.gov ID: Yale5062786