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

NCT00090545 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 04026204-C-0262
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostate Cancer

Keywords

Hormone-Refractory; Proteomics; Angiogenesis; VEGFR; Prostate Cancer; Metastatic Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  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 Outcomes (6)

• Number of Participants With Adverse Events

  Date treatment consent signed to date off study, approximately 49 months.

• Median Overall Survival

  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)

  Every 2 cycles (1 cycle = 28 days)

• 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

• 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

Study Arms (2)

First Stage - disease progression

EXPERIMENTAL

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

Second Stage - increased accrual

EXPERIMENTAL

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

Interventions

BAY 43-9006 DRUG

400 mg BAY 43-9006 orally twice daily in 28 day cycles.

Also known as: sorafenib

First Stage - disease progression; Second Stage - increased accrual

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Cancer Institute (NCI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (9)

• Klotz L. Hormone therapy for patients with prostate carcinoma. Cancer. 2000 Jun 15;88(12 Suppl):3009-14. doi: 10.1002/1097-0142(20000615)88:12+3.3.co;2-5.

  PMID: 10898345 BACKGROUND

• Peer CJ, Sissung TM, Kim A, Jain L, Woo S, Gardner ER, Kirkland CT, Troutman SM, English BC, Richardson ED, Federspiel J, Venzon D, Dahut W, Kohn E, Kummar S, Yarchoan R, Giaccone G, Widemann B, Figg WD. Sorafenib is an inhibitor of UGT1A1 but is metabolized by UGT1A9: implications of genetic variants on pharmacokinetics and hyperbilirubinemia. Clin Cancer Res. 2012 Apr 1;18(7):2099-107. doi: 10.1158/1078-0432.CCR-11-2484. Epub 2012 Feb 3.

  PMID: 22307138 BACKGROUND

• Jain L, Woo S, Gardner ER, Dahut WL, Kohn EC, Kummar S, Mould DR, Giaccone G, Yarchoan R, Venitz J, Figg WD. Population pharmacokinetic analysis of sorafenib in patients with solid tumours. Br J Clin Pharmacol. 2011 Aug;72(2):294-305. doi: 10.1111/j.1365-2125.2011.03963.x.

  PMID: 21392074 BACKGROUND

• Jain L, Sissung TM, Danesi R, Kohn EC, Dahut WL, Kummar S, Venzon D, Liewehr D, English BC, Baum CE, Yarchoan R, Giaccone G, Venitz J, Price DK, Figg WD. Hypertension and hand-foot skin reactions related to VEGFR2 genotype and improved clinical outcome following bevacizumab and sorafenib. J Exp Clin Cancer Res. 2010 Jul 14;29(1):95. doi: 10.1186/1756-9966-29-95.

  PMID: 20630084 BACKGROUND

• Azad NS, Aragon-Ching JB, Dahut WL, Gutierrez M, Figg WD, Jain L, Steinberg SM, Turner ML, Kohn EC, Kong HH. Hand-foot skin reaction increases with cumulative sorafenib dose and with combination anti-vascular endothelial growth factor therapy. Clin Cancer Res. 2009 Feb 15;15(4):1411-6. doi: 10.1158/1078-0432.CCR-08-1141.

  PMID: 19228742 BACKGROUND

• Jain L, Gardner ER, Venitz J, Dahut W, Figg WD. Development of a rapid and sensitive LC-MS/MS assay for the determination of sorafenib in human plasma. J Pharm Biomed Anal. 2008 Jan 22;46(2):362-7. doi: 10.1016/j.jpba.2007.10.027.

  PMID: 18309574 BACKGROUND

• Kong HH, Cowen EW, Azad NS, Dahut W, Gutierrez M, Turner ML. Keratoacanthomas associated with sorafenib therapy. J Am Acad Dermatol. 2007 Jan;56(1):171-2. doi: 10.1016/j.jaad.2006.10.032. No abstract available.

  PMID: 17190642 BACKGROUND

• Aragon-Ching JB, Jain L, Gulley JL, Arlen PM, Wright JJ, Steinberg SM, Draper D, Venitz J, Jones E, Chen CC, Figg WD, Dahut WL. Final analysis of a phase II trial using sorafenib for metastatic castration-resistant prostate cancer. BJU Int. 2009 Jun;103(12):1636-40. doi: 10.1111/j.1464-410X.2008.08327.x. Epub 2009 Jan 9.

  PMID: 19154507 RESULT

• Dahut WL, Scripture C, Posadas E, Jain L, Gulley JL, Arlen PM, Wright JJ, Yu Y, Cao L, Steinberg SM, Aragon-Ching JB, Venitz J, Jones E, Chen CC, Figg WD. A phase II clinical trial of sorafenib in androgen-independent prostate cancer. Clin Cancer Res. 2008 Jan 1;14(1):209-14. doi: 10.1158/1078-0432.CCR-07-1355.

  PMID: 18172272 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: William Dahut, M.D.
• Organization: National Cancer Institute, National Institues of Health

dahutw@mail.nih.gov

301-435-8183

Study Officials

• William Dahut, M.D.

  National Cancer Institute, National Institutes of Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 27, 2004
• First Posted: August 27, 2004
• Study Start: September 1, 2004
• Primary Completion: September 1, 2007
• Study Completion: April 1, 2009
• Last Updated: June 14, 2018
• Results First Posted: September 28, 2012

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)