Sorafenib in Treating Patients With Metastatic or Recurrent Prostate Cancer

A Phase II Study Of BAY 43-9006 (NSC 724772; CTEP IND# 69,896) In Patients With Hormone Refractory Prostate Cancer

RATIONALE: Sorafenib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

PURPOSE: This phase II trial is studying the effectiveness of sorafenib in treating patients who have metastatic or recurrent prostate cancer that has not responded to previous hormone therapy.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: sorafenib tosylate

Detailed Description

OBJECTIVES:

• Determine the efficacy of sorafenib, as measured by prostate-specific antigen response, in patients with metastatic or recurrent hormone-refractory adenocarcinoma of the prostate.

Secondary

• Determine the objective response rate and duration of response in patients treated with this drug.
• Determine the tolerability and toxicity of this drug in these patients.
• Determine time to treatment failure and overall survival in patients treated with this drug.
• Explore the relationship between measures of ras/raf pathway activation (pERK) and response to treatment in these patients.

OUTLINE: This is a non-randomized, multicenter study.

Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed at 4 weeks after going off study treatment and then periodically for survival. Patients with stable or responding disease, when they go off study treatment, are followed every 3 months until relapse or progression.

PROJECTED ACCRUAL: Approximately 15-25 patients will be accrued for this study within 12-18 months.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre - Calgary
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • British Columbia Cancer Agency - Centre for the Southern Interior
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • British Columbia Cancer Agency - Vancouver Cancer Centre
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Margaret and Charles Juravinski Cancer Centre
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program at London Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

  • Metastatic or recurrent disease
• No curative standard therapy exists

• Hormone-refractory disease

  • Evidence of prostate-specific antigen (PSA) progression during androgen ablation therapy, including medical or surgical castration

    • Documented PSA progression after completion of prior peripheral anti-androgens

      • At least a 25% increase (≥ 5 ng/mL) over a reference value PSA with 2 consecutive rising PSAs taken ≥ 1 week apart

    • Castrate level of testosterone ≤ 1.7 nmol/L for patients on medical androgen ablation

      • Patients receiving luteinizing hormone-releasing hormone agonist therapy must continue this treatment during study participation
• PSA ≥ 10 ng/mL at the time of study entry
• Primary tumor tissue (paraffin embedded) must be available for immunohistochemistry

• Minimal symptomatic disease

  • No requirement for morphine or equivalent dose > 30 mg/day to control pain
• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• No evidence of bleeding diathesis

Hepatic

• Bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal

Renal

• Serum creatinine normal OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No myocardial infarction within the past 6 months
• No congestive heart failure
• No unstable angina
• No active cardiomyopathy
• No unstable ventricular arrhythmia
• No uncontrolled hypertension

Other

• No serious infection
• No active peptic ulcer disease
• No upper gastrointestinal or other condition that would preclude study compliance with oral medication
• No uncontrolled psychotic disorder
• No history of allergic reaction attributed to compounds of similar chemical or biologic composition to sorafenib or other study agents
• No other serious illness or medical condition that would preclude study participation
• No other malignancy within the past 5 years except adequately treated non-melanoma skin cancer or other curatively treated solid tumor

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Concurrent prophylactic filgrastim (G-CSF), sargramostim (GM-CSF), or other growth factors allowed for the management of adverse events only

Chemotherapy

• No prior chemotherapy
• No other prior cytotoxic chemotherapy

Endocrine therapy

• See Disease Characteristics
• Concurrent steroids allowed provided there has been no increase in steroid requirements within the past 4 weeks AND no increase in dose is planned

Radiotherapy

• At least 4 weeks since prior external-beam radiotherapy except low-dose non-myelosuppressive radiotherapy
• Concurrent low-dose non-myelosuppressive palliative radiotherapy allowed

Surgery

• Not specified

Other

• No prior investigational anticancer agents

• No concurrent therapeutic anticoagulation

  • Concurrent prophylactic low-dose warfarin for venous or arterial access devices allowed
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent anticancer therapy
• No other concurrent investigational therapy
• No concurrent grapefruit juice
• Concurrent bisphosphonates allowed

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Prostate-specific antigen response and/or progression	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective response and/or progression	2 years
Tolerability and toxicity	2 years
Time to treatment failure and overall patient survival	2 years

Collaborators and Investigators

• Sponsor: NCIC Clinical Trials Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Kim N. Chi, MD, British Columbia Cancer Agency

Publications and helpful links

General Publications

• Chi KN, Ellard SL, Hotte SJ, Czaykowski P, Moore M, Ruether JD, Schell AJ, Taylor S, Hansen C, Gauthier I, Walsh W, Seymour L. A phase II study of sorafenib in patients with chemo-naive castration-resistant prostate cancer. Ann Oncol. 2008 Apr;19(4):746-51. doi: 10.1093/annonc/mdm554. Epub 2007 Dec 3.

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2004
• Primary Completion (Actual): September 28, 2006
• Study Completion (Actual): January 18, 2011

Study Registration Dates

• First Submitted: October 6, 2004
• First Submitted That Met QC Criteria: October 7, 2004
• First Posted (Estimated): October 8, 2004

Study Record Updates

• Last Update Posted (Actual): August 4, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: stage IV prostate cancer; recurrent prostate cancer; adenocarcinoma of the prostate
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: I167; CAN-NCIC-IND167 (Other Identifier: PDQ); CDR0000387987 (Other Identifier: PDQ)

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