Clinical trial NCT00093457: Sorafenib in Treating Patients With Metastatic or Recurrent Prostate Cancer
Official title: A Phase II Study Of BAY 43-9006 (NSC 724772; CTEP IND# 69,896) In Patients With Hormone Refractory Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: recurrent prostate cancer
stage IV prostate cancer
adenocarcinoma of the prostate
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-10-08
Enrollment: 28
Sex: MALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Prostate-specific antigen response and/or progression
timeFrame: 2 years
Secondary outcomes:
measure: Objective response and/or progression
timeFrame: 2 years
measure: Tolerability and toxicity
timeFrame: 2 years
measure: Time to treatment failure and overall patient survival
timeFrame: 2 years
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre - Calgary
state: Alberta
city: Kelowna
country: Canada
facility: British Columbia Cancer Agency - Centre for the Southern Interior
state: British Columbia
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency - Vancouver Cancer Centre
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Hamilton
country: Canada
facility: Margaret and Charles Juravinski Cancer Centre
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Program at London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: British Columbia Cancer Agency
name: Kim N. Chi, MD
role: STUDY_CHAIR
References:
citation: 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.