Clinical trial NCT00031889: Exemestane With or Without Bicalutamide in Treating Patients With Stage IV Prostate Cancer
Official title: A Randomized Phase II Trial of Exemestane With and Without Bicalutamide as Second Line Therapy After Failure of Androgen Suppression in Advanced Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
stage IV prostate cancer
recurrent prostate cancer
Lead sponsor: Swiss Group for Clinical Cancer Research
Sponsor class: OTHER
First posted: 2003-07-01
Enrollment: 5
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Hormone therapy using exemestane plus bicalutamide may fight prostate cancer by reducing the production of androgens. It is not yet known if exemestane is more effective with or without bicalutamide in treating prostate cancer.

PURPOSE: Randomized phase II trial to study the effectiveness of exemestane with or without bicalutamide in treating patients who have stage IV prostate cancer that has been previously treated with hormone therapy or surgery.

Detailed description: OBJECTIVES:

* Compare the efficacy and tolerability of exemestane with or without bicalutamide as second-line therapy after failure of androgen suppression (luteinizing hormone-releasing hormone agonist or orchiectomy) in patients with stage IV prostate cancer.
* Determine the potential antagonistic effect of the weak androgen action of exemestane when combined with bicalutamide in these patients.
* Compare the quality of life (QOL) in patients treated with these regimens.
* Correlate prostate-specific antigen response and data of QOL, including scores for pain intensity and analgesic consumption, in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to performance status (0 vs 1-2), pain (none or mild vs moderate or severe), and participating center. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive oral exemestane once daily.
* Arm II: Patients receive exemestane as in arm I and oral bicalutamide once daily.

Treatment in both arms continues every 4 weeks for a minimum of 2 courses in the absence of disease progression or unacceptable toxicity.

Quality of life and pain are assessed at baseline, on day 1 of course 2 and any subsequent courses, and at disease progression or treatment failure (if applicable).

Patients are followed monthly until disease progression.

PROJECTED ACCRUAL: A total of 20-62 patients (10-31 per treatment arm) will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed stage IV adenocarcinoma of the prostate
* Documented disease progression based on prostate-specific antigen (PSA) progression during first-line androgen suppression (luteinizing hormone-releasing hormone agonist or orchiectomy)

  * PSA progression is defined by the following:

    * Interval of at least 1 week between reference value (time point value 1) and the next PSA level (time point value 2)
    * PSA at time point value 3 is greater than PSA at time point value 2 OR
    * PSA at time point value 3 is not greater than PSA at time point value 2, but PSA at time point value 4 is greater than PSA at time point value 2
* PSA at least 5 ng/mL
* Must continue primary androgen suppression if no prior surgical castration
* No known leptomeningeal or brain metastases

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* WHO 0-2

Life expectancy:

* Not specified

Hematopoietic:

* WBC at least 3,500/mm\^3
* Neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3
* Hemoglobin at least 9 g/dL

Hepatic:

* Bilirubin no greater than 1.5 times upper limit of normal (ULN)
* AST and ALT no greater than 2.5 times ULN

Renal:

* Creatinine no greater than 1.5 times ULN

Other:

* No acute concurrent severe infection
* No other concurrent significant disease that would preclude study therapy
* No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No prior antibody or gene therapy

Chemotherapy:

* No prior cytostatic agents

Endocrine therapy:

* See Disease Characteristics
* No prior estramustine
* No prior antiandrogens (e.g., bicalutamide)
* No concurrent estrogen-containing medicine

Radiotherapy:

* More than 4 weeks since prior radiotherapy
* No concurrent radiotherapy to more than 1 field

Surgery:

* See Disease Characteristics

Other:

* At least 4 weeks since prior investigational drugs

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Aarau
country: Switzerland
facility: Kantonspital Aarau
city: Basel
country: Switzerland
facility: University Hospital
city: Bern
country: Switzerland
facility: Inselspital, Bern
city: Biel
country: Switzerland
facility: Spitalzentrum Biel
city: Bruderholz
country: Switzerland
facility: Kantonsspital Bruderholz
city: Chur
country: Switzerland
facility: Ratisches Kantons und Regionalspital
city: Genolier
country: Switzerland
facility: Clinique De Genolier
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Lugano
country: Switzerland
facility: Istituto Oncologico della Svizzera Italiana
city: Mendrisio
country: Switzerland
facility: Ospedale Beata Vergine
city: Sion
country: Switzerland
facility: Institut Central des Hopitaux Valaisans
city: Zurich
country: Switzerland
facility: Universitaetsspital
Study officials:
affiliation: Ospedale Beata Vergine
name: Marco Bonomo, MD
role: STUDY_CHAIR
References: