Effect of BAY 43-9006 (Sorafenib) on Cardiovascular Safety Parameters in Cancer Patients

Study Overview
=================
Brief Summary
-----------------
This is an open-label, non-randomized Phase I study of sorafenib 400 mg bid (2 x 200 mg tablets) in cancer patients. The primary objective of the study is to evaluate the effect of sorafenib on cardiovascular safety parameters. The secondary objectives are to evaluate the safety, pharmacokinetics, and anti-tumor activity of sorafenib in cancer patients

Official Title
-----------------
Effect of BAY 43-9006 (Sorafenib) on Cardiovascular Safety Parameters in Cancer Patients

Conditions
-----------------
Neoplasms

Intervention / Treatment
-----------------
* Drug: Sorafenib (Nexavar, BAY43-9006)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with refractory solid cancer for which curative or palliative measures have failed or patients for whom standard treatment is considered ineffective or intolerable Histological or cytological documentation of cancer is required Patients with at least one evaluable lesion. Lesions must be evaluated by Computed Tomography (CT) scan or Magnetic Resonance Imaging (MRI) Life expectancy of at least 12 weeks Left ventricular ejection fraction (LVEF) >=45 % as assessed at the Baseline Multiple Gated Acquisition (MUGA) scan Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to dosing: Hemoglobin > 9.0 g/dL Absolute neutrophil count (ANC) > 1,500/mm3 Platelet count >=100,000/dL Total bilirubin <=1.5 times the upper limit of normal Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) <=2.5 x upper limit of normal, except if there is metastatic disease to the liver, in which case <=5 x upper limit of normal is acceptable Prothrombin Time-International Normalized Ratio/Partial Thromboplastin Time (PT-INR/PTT) < 1.5 x upper limit of normal. Patients who are being therapeutically anticoagulated with an agent such as Coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists. For patients on anticoagulation therapy, at least weekly evaluations will be performed until International Normalized Ratio (INR) is stable as defined by the local standard of care Serum creatinine <=1.5 x upper limit of normal Exclusion Criteria: Colorectal cancer whether refractory or not Supine systolic blood pressure greater than 170 mmHg or diastolic blood pressure greater than 100 mmHg (mean of duplicate readings) at Screening with or without antihypertensives Symptomatic metastatic brain or meningeal tumors Pregnant or breast-feeding patients

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: Sorafenib (Nexavar, BAY43-9006)<br>* Sorafenib 400 mg twice a day (bid) (2 x 200 mg tablets)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of sorafenib on cardiovascular safety parameters |  | up to 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics |  | after 16 months | 
| Anti-tumor activity |  | after 10 months | 
| Adverse Event Collection |  | after 11 months |