A Phase II Study of BAY 43-9006 (Sorafenib) in Metastatic, Androgen-Independent Prostate Cancer

Phase 2

Completed

Conditions: Prostate Cancer

Interventions: Drug: BAY 43-9006

Registration Number: NCT00090545

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: BAY 43-9006 (Sorafenib) is an experimental cancer drug produced by Bayer Health Care Corporation. It represents a new class of anticancer agents known as bi-aryl ureas. This study will investigate its effect on prostate cancer and its side effects. Researchers expect to enroll a maximum of 46 men with prostate cancer for this study. The duration of the study will depend on its results.

Before beginning to take the drug, patients will be admitted to the hospital for 2 days, have a medical examination and give blood samples, and have a tumor or bone marrow biopsy. On the first day of the study, patients will begin taking the drug as 2 tablets twice daily, morning and evening. Blood will be taken throughout the day to determine the drug's level in the bloodstream.

Patients will be discharged from the hospital on the second day, and will continue to take the drug twice daily until instructed to stop. During each of the first 4 weeks, patients will be required to have their blood pressure checked. At the end of the first 4 weeks, patients will have a physical examination and blood tests, as well as a second tumor or bone marrow biopsy.

After the first 4 weeks, patients will continue with their drug regimen. At the end of each 4-week cycle, patients will have a physical examination and blood tests. Patients will also have x-Rays, computed tomography (CT) scans, and/or magnetic resonance imaging (MRIs) at every other 4-week examination or as required. Patients will be asked to keep a diary recording the time and amount of their medication for this study.

Detailed Description: BAY 43-9006 (Sorafenib) is a potent inhibitor of wild-type and mutant b-Raf and c-Raf kinase isoforms in vitro. In addition, this agent also inhibits p38, c-kit, vascular endothelial growth factor receptor 2 (VEGFR-2) and platelet-derived growth factor receptor beta (PDGFR-beta) affecting tumor growth as well as possibly promoting apoptosis by events downstream of c-Raf. At this time, over 500 patients have been treated with this drug with tolerable side effects.

The primary objective of this study is to determine if BAY 43-9006 (Sorafenib) is associated with a 50% 4 month probability of progression free survival in patients with metastatic androgen independent prostate cancer (AIPC) as determined by clinical, radiographic, and prostatic specific antigen (PSA) criteria.

The secondary objective of this study will be demonstration of biologic effect by the drug in the patient and on the tumor (when possible). Correlative studies will be conducted on serially obtained tissue biopsies, bone marrow biopsies, and white blood cell collections. These laboratory correlates will include elucidation of activation of components of the Raf-extracellular-signal regulated kinase (ERK)-methyl ethyl ketone (MEK) and angiogenesis pathways using protein microarray technologies developed by the National Cancer Institute (NCI)/Food and Drug Administration (FDA) clinical proteomics program.

Per Amendment D, a secondary objective of this study will also be to determine the time to progression measured by clinical and radiographic criteria. The 22 patients treated on the first stage of this protocol will be retrospectively evaluated with respect to this secondary endpoint possible. Please refer to the statistics section for further details.

The combination of correlated clinical and laboratory endpoints with emphasis on molecular signaling will provide new information on the anti-tumor effects helping to characterize its role in the treatment of androgen independent prostate cancer (AIPC).

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 46

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
First Stage - disease progression	BAY 43-9006	The first stage was to rule out the probability of 4 month progression free survival. Patients were given 400 mg BAY 43-9006 orally twice daily in 28 day cycles.
Second Stage - increased accrual	BAY 43-9006	Due to prostatic specific antigen and radiographic discordance during the first stage, the protocol was amended to allow accrual to a second stage. Patients were given 400 mg BAY 43-9006 orally twice daily in 28 day cycles.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival	4 months	Determine whether BAY 43-9006 when used to treat metastatic prostate cancer is associated with having 50% of Patients Progression Free at 4 Months by clinical, radiographic, and prostatic specific antigen (PSA)criteria.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	Date treatment consent signed to date off study, approximately 49 months.	Here is the number of participants with adverse events. For the detailed list of adverse events, see the adverse event module.
Maximum Observed Plasma Concentration (Cmax) of BAY 43-9006 (Sorafenib)	0, 0.25, 0.50, 1, 2, 4, 6, 8, 12, AND 24 hours post dose	Plasma concentration-time profile for sorafenib.
Median Overall Survival	Time from treatment start date until date of death or date last known alive, approximately 18.3 months.	Time from treatment start date until date of death or date last known alive.
Overall Response Evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST)	Every 2 cycles (1 cycle = 28 days)	Overall response was evaluated by the RECIST. Complete Response (CR) is the disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Geometric Mean for Exposure Area Under the Curve (AUC) 0-12	0, 0.25, 0.50, 1, 2, 4, 6, 8, 12, and 24 hours post-dose	Geometric mean exposure for sorafenib.
Time to Maximum Observed Plasma Concentration (Tmax) of BAY 43-9006 (Sorafenib)	0, 0.25, 0.50, 1, 2, 4, 6, 8, 12, and 24 hours post-dose	Time to maximum concentration for sorafenib.