Sorafenib Tosylate in Treating Patients With Recurrent Aggressive Non-Hodgkin's Lymphoma

PRIMARY OBJECTIVES:

I. To evaluate the response rate of treatment with sorafenib (BAY43-9006) in patients with
recurrent aggressive non-Hodgkin's lymphomas.

SECONDARY OBJECTIVES:

I. To evaluate the duration of response and progression free survival of treatment with
BAY43-9006 in patients with recurrent aggressive Non-Hodgkin's Lymphomas.

II. To characterize the toxicity of treatment with BAY43-9006 in patients with recurrent
aggressive Non-Hodgkin's Lymphomas.

III. To further characterize the pharmacokinetics properties of BAY43-9006 and assess
influence of monooxygenases polymorphisms and multi-drug resistance transporter (MDR) on
pharmacokinetics.

OUTLINE: This is a multicenter study.

Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in
the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and
then every 6 months for 1 year.

PLANNED ACCRUAL: 41 ACTUAL ACCRUAL: 14

Inclusion Criteria:

- Patients must have histologically confirmed recurrent de novo or transformed diffuse
large B cell lymphoma (DLBCL) or one of its variants according to WHO classification
(centroblastic, immunoblastic, T-cell/histiocyte rich and anaplastic variants)

- Eastern Cooperative Oncology Group (ECOG) performance status must be 0 or 1

- Patients must have measurable disease as defined in section 6 assessed within 4 weeks
of registration

- Patients must have failed one or more prior Non-Hodgkin lymphoma (NHL) chemotherapy
or antibody therapy with curative intent; autologous stem cell transplant is
permitted

- Leukocytes >= 2,000/mm^3

- Absolute neutrophil count >= 1,000/mm^3

- Platelets >= 75,000/ mm^3

- Total bilirubin =< 2.0 X normal institutional limits

- Aspartate Aminotransferase (AST) =< 2.5 X institutional upper limit of normal

- Alanine Aminotransferase (ALT) =< 2.5 X institutional upper limit of normal

- Creatinine within normal institutional limits; creatinine clearance calculated or
measured at >= 60 ml/min/1.73m^2 if creatinine level is above institutional limits

- The prothrombin time (PT)/international normalized ratio (INR) within Institutional
limits of normal

- Patients with underlying hypertension as defined by blood pressures averaging greater
than 140/90 on two separate clinic visits are eligible if hypertension has been
controlled by standard nonpharmacologic and pharmacologic therapy

- Patients must be physically able to orally ingest tablets

Exclusion Criteria:

- Central nervous system (CNS) involvement

- Previously treated with Sorafenib (BAY 43-9006) or other small molecule targeted
inhibitors of mitogen-activated protein kinase (MAPK) signaling intermediates or
angiogenesis (e.g. bevacizumab)

- Progressed within 60 days of last therapy

- Prior allogeneic stem cell transplant

- Candidates for potentially curative therapy, such as hematopoietic stem cell
transplantation (HSCT)

- Currently receiving any other investigational agents

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to sorafenib

- Uncontrolled intercurrent illness including, but not limited to: ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia or psychiatric illness/social situations that would limit compliance with
study requirements

- Active HIV infection, because of possible pharmacokinetic interactions of
anti-retroviral therapy with BAY43-9006

- Evidence of bleeding diathesis

- Currently taking the cytochrome P450 enzyme-inducing anti-epileptic drugs (phenytoin,
carbamazepine and phenobarbital), rifampin or St. John's Wort

- Pregnant or Breast-feeding; all females of childbearing potential must have a blood
test or urine study within 2 weeks prior to registration to rule out pregnancy. Women
of childbearing potential and sexually active males must be strongly advised to use
an accepted and effective method of contraception