Sorafenib in Treating Patients With Metastatic or Unresectable Solid Tumors, Multiple Myeloma, or Non-Hodgkin's Lymphoma With or Without Impaired Liver or Kidney Function
Sorafenib in Treating Patients With Metastatic or Unresectable Solid Tumors, Multiple Myeloma, or Non-Hodgkin's Lymphoma With or Without Impaired Liver or Kidney Function
This phase I trial is studying the side effects and best dose of sorafenib in treating
 patients with metastatic or unresectable solid tumors, multiple myeloma, or non-Hodgkin's
 lymphoma with or without impaired liver or kidney function. Sorafenib may stop the growth of
 cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood
 flow to the cancer. Sorafenib may have different effects in patients who have changes in
 their liver or kidney function
PRIMARY OBJECTIVES:

 I. To characterize the pharmacokinetics of BAY 43-9006 in patients with hepatic or renal
 dysfunction (part 1 of the study).

 II. To determine a tolerable starting dose of BAY 43-9006 in patients with varying degrees of
 hepatic or renal dysfunction (part 2 of the study).

 OUTLINE: This is a dose-escalation, multicenter study. Patients are assigned to 1 of 9
 treatment cohorts according to hepatic or renal function.

 Patients receive oral sorafenib once on day 1 and then once daily, twice daily, or every
 other day beginning on day 8 and continuing for 3 months. Patients are re-evaluated at 3
 months. Patients with responding disease may continue study treatment in the absence of
 disease progression or unacceptable toxicity.

 Cohorts of 3-6 patients (per treatment cohort) receive escalating doses of sorafenib until
 the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that
 at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are
 treated at the MTD.

 PROJECTED ACCRUAL: A total of 120 patients will be accrued for this study.
Inclusion Criteria:

 -  Patients must have cytologically or histologically confirmed tumors that are
 metastatic or unresectable and for which standard curative or palliative measures do
 not exist or are no longer effective; Patients with solid tumors, multiple myeloma, or
 non-Hodgkin's lymphoma are eligible

 -  Lesions that can be accurately measured in at least one dimension (longest diameter to
 be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan

 -  All other lesions, including small lesions (longest diameter < 20 mm with conventional
 techniques or < 10 mm with spiral CT scan) and truly nonmeasurable lesions; Lesions
 that are considered non-measurable include the following:

 -  Bone lesions

 -  Ascites

 -  Pleural/pericardial effusion

 -  Lymphangitis cutis/pulmonis

 -  Abdominal masses that are not confirmed and followed by imaging techniques

 -  Cystic lesions

 -  ≥ 4 weeks since major surgery

 -  ≥ 4 weeks since completion of radiation or chemotherapy except for ≥ 6 weeks for
 nitrosoureas, L-PAM or mitomycin-C

 -  ECOG Performance Status of 0-2

 -  Non-pregnant and non-nursing because the effects of BAY 43-9006 on the fetus/infant
 are unknown; in addition, women of child-bearing potential and men must agree to use
 an appropriate method of birth control throughout their participation in this study;
 appropriate methods of birth control include abstinence, oral contraceptives,
 implantable hormonal contraceptives (Norplant), or double barrier methods (diaphragm
 plus condom)

 -  No patients with uncontrolled intercurrent illness including, but not limited to,
 ongoing or active infection, symptomatic congestive heart failure, unstable angina
 pectoris, cardiac arrhythmia, uncontrolled hypertension, or psychiatric illness/social
 situations that would limit compliance with study requirements

 -  No concomitant medications known to cause hepatic or renal toxicity, including
 anti-seizure medications, non-steroidal anti-inflammatory agents, and steroids

 -  No gastrointestinal tract disease resulting in an inability to take oral medication or
 a requirement for IV alimentation, prior surgical procedures affecting absorption, or
 active peptic ulcer disease

 -  No HIV-positive patients receiving combination anti-retroviral therapy because of
 possible pharmacokinetic interactions with BAY 43-9006; however, patients who are HIV+
 but without AIDS defining diagnosis and not on combination anti-retroviral therapy are
 eligible

 -  No patients with evidence of biliary or renal obstruction; patients should be observed
 for at least one week after treatment (i.e. stents or drains) for biliary or renal
 obstruction to ensure their organ dysfunction has stabilized before registration to
 this protocol

 -  No current treatment with other investigational agents

 -  No evidence of bleeding diathesis

 -  No patients on therapeutic anticoagulation; prophylactic anticoagulation (i.e., low
 dose warfarin) of venous or arterial access devices is allowed provided that the
 requirements for PT, INR or PTT is met

 -  No treatment with cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin,
 carbamazepine or Phenobarbital), rifampin or St. John's wort

 -  Patients with brain metastases are eligible if they meet all of the following
 criteria:

 -  Asymptomatic

 -  Radiographically stable disease for at least 2 months

 -  Previously received treatment for the brain metastases

 -  Not currently receiving steroid therapy or enzyme-inducing anticonvulsants (e.g.
 phenytoin, phenobarbital, or carbamazepine)

 -  Granulocytes ≥ 1,500/μl

 -  Platelet count ≥ 75,000/μl

 -  Normal or abnormal organ function