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

June 12, 2018 updated by: William Dahut Jr., M.D., National Cancer Institute (NCI)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

46

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Cancer Institute (NCI)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

  • INCLUSION CRITERIA

Patients must have histopathological confirmation of prostate cancer by the Laboratory of Pathology of the National Cancer Institute (NCI) or Pathology Department of the National Naval Medical Center prior to entering this study. Patients whose pathology specimens are no longer available may be enrolled in the trial if the patient has a clinical course consistent with prostate cancer and available documentation from an outside pathology laboratory of the diagnosis. In cases where original tissue blocks or archival biopsy material is available, all efforts should be made to have the material forwarded to the research team for use in correlative studies.

Patients must have metastatic progressive androgen-independent prostate cancer. There must be radiographic evidence of disease after primary treatment with either surgery or radiotherapy that has continued to progress despite hormonal agents. Progression requires that a measurable lesion is expanding, new lesions have appeared, and/or that prostatic specific antigen (PSA) is continuing to rise on successive measurements. Patients on flutamide must have disease progression at least 4 weeks after withdrawal. Patients on bicalutamide or nilutamide must have progression at least 6 weeks after withdrawal.

Patients may have had no more than 1 previous cytoxic chemotherapeutic line.

Because no dosing or adverse event data are currently available on the use of BAY 43-9006 (Sorafenib) in patients less than 18 years of age, children are excluded from this study.

Patients must have a life expectancy of more than 3 months.

Patients must have a performance status of 0 to 2 according to the Eastern Cooperative Oncology Group (ECOG) criteria.

Patient must have adequate organ function as defined below:

Leukocytes greater than or equal to 3,000/microL

Absolute neutrophil count greater than or equal to 1,500/microL

Platelets greater than or equal to 100,000/microL

Total bilirubin less than or equal to 1.5 X institutional upper limits of normal

Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase(SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase(SGPT) less than or equal to 2.5 X institutional upper limit of normal

Creatinine less than or equal to 1.5 X institutional upper limits of normal OR:

Creatinine clearance greater than or equal to 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal.

Patients must have recovered from any acute toxicity related to prior therapy, including surgery. Toxicity should be less than or equal to grade 1 or returned to baseline.

Hormonal profile: all patients who have not undergone bilateral surgical castration must continue suppression of testosterone production by appropriate usage of gonadotropin releasing hormone (GnRH) agonists.

Patients must not have other invasive malignancies (within the past two years with the exception of non-melanoma skin cancers or non-invasive bladder cancer).

Patients must be able to understand and sign an informed consent form.

Concurrent use of bisphosphonates will be allowed for patients with known bone metastases

Patients who require hematopoietic growth factor support (e.g. epogen, darbepoetin), non-steroidal anti-inflammatory drug (NSAIDs), and other maintenance medications prior to study entry will be allowed to continue their supportive therapies.

The effects of BAY 43-9006 (Sorafenib) on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because Raf-kinase inhibitors are known to be teratogenic, men must agree to use adequate contraception (abstinence; hormonal or barrier method of birth control) prior to study entry and for the duration of study participation.

EXCLUSION CRITERIA

Patients who have had chemotherapy or radiotherapy (including radioisotopes) within 4 weeks (6 weeks for nitrosoureas or mitomycin C, greater than 3 months for suramin) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.

Patients may not be receiving any other investigational agents.

Patients with known brain metastases are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to BAY 43-9006 (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.

Hypertension as defined by systolic blood pressure in excess of 170 mmHg or diastolic pressure in excess of 100 mmHg. Patients with a history of hypertension that is well controlled on medication will not be excluded. Patients may not be on either verapamil or diltiazem while on study. Use of calcium channel blocker should be discouraged.

Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy. Therefore, human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with BAY 43-9006 (Sorafenib). Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated.

History of bleeding diathesis

Patients on therapeutic anticoagulation are at increased risk from bleeding while on BAY 43-9006 (Sorafenib). Prophylactic anticoagulation (i.e. low dose warfarin) of venous or arterial access devices is allowed provided that the requirements for prothrombin time (PT), International normalized ratio (INR) or partial thromboplastin time (PTT) are met: PT less than 1.1 x institutional upper limit of normal; INR less than 1.1; PTT within the institutional limits of normal. These requirements will only be made upon those patients on warfarin.

INCLUSION OF WOMEN AND MINORITIES

Men of all races and ethnic groups are eligible for this trial. Women are excluded by the nature of the disease.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: First Stage - disease progression

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.
Drug: BAY 43-9006
400 mg BAY 43-9006 orally twice daily in 28 day cycles.
Other Names:
  • sorafenib
Experimental: Second Stage - increased accrual

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.
Drug: BAY 43-9006
400 mg BAY 43-9006 orally twice daily in 28 day cycles.
Other Names:
  • sorafenib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: 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.
4 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Adverse Events
Time Frame: 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.
Date treatment consent signed to date off study, approximately 49 months.
Median Overall Survival
Time Frame: 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.
Time from treatment start date until date of death or date last known alive, approximately 18.3 months.
Overall Response Evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame: 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.
Every 2 cycles (1 cycle = 28 days)
Maximum Observed Plasma Concentration (Cmax) of BAY 43-9006 (Sorafenib)
Time Frame: 0, 0.25, 0.50, 1, 2, 4, 6, 8, 12, AND 24 hours post dose
Plasma concentration-time profile for sorafenib.
0, 0.25, 0.50, 1, 2, 4, 6, 8, 12, AND 24 hours post dose
Geometric Mean for Exposure Area Under the Curve (AUC) 0-12
Time Frame: 0, 0.25, 0.50, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
Geometric mean exposure for sorafenib.
0, 0.25, 0.50, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
Time to Maximum Observed Plasma Concentration (Tmax) of BAY 43-9006 (Sorafenib)
Time Frame: 0, 0.25, 0.50, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
Time to maximum concentration for sorafenib.
0, 0.25, 0.50, 1, 2, 4, 6, 8, 12, and 24 hours post-dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: William Dahut, M.D., National Cancer Institute, National Institutes of Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2004

Primary Completion (Actual)

September 1, 2007

Study Completion (Actual)

April 1, 2009

Study Registration Dates

First Submitted

August 27, 2004

First Submitted That Met QC Criteria

August 26, 2004

First Posted (Estimate)

August 27, 2004

Study Record Updates

Last Update Posted (Actual)

June 14, 2018

Last Update Submitted That Met QC Criteria

June 12, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 040262
  • 04-C-0262

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Prostate Cancer

Clinical Trials on BAY 43-9006

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Qatar

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe