Exemestane With or Without Bicalutamide in Treating Patients With Stage IV Prostate Cancer

A Randomized Phase II Trial of Exemestane With and Without Bicalutamide as Second Line Therapy After Failure of Androgen Suppression in Advanced Prostate Cancer

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.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Exemestane; Drug: Exemestane+bicalutamide

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Aarau, Switzerland, 5001
    • Kantonspital Aarau
  • Basel, Switzerland, CH-4031
    • University Hospital
  • Bern, Switzerland, CH-3010
    • Inselspital, Bern
  • Biel, Switzerland, CH-2500
    • Spitalzentrum Biel
  • Bruderholz, Switzerland, CH-4101
    • Kantonsspital Bruderholz
  • Chur, Switzerland, CH-7000
    • Ratisches Kantons und Regionalspital
  • Genolier, Switzerland, Ch-1272
    • Clinique De Genolier
  • Lausanne, Switzerland, CH-1011
    • Centre Hospitalier Universitaire Vaudois
  • Lugano, Switzerland, CH-6900
    • Istituto Oncologico della Svizzera Italiana
  • Mendrisio, Switzerland, CH-6850
    • Ospedale Beata Vergine
  • Sion, Switzerland, CH1951
    • Institut Central des Hopitaux Valaisans
  • Zurich, Switzerland, CH-8091
    • UniversitaetsSpital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I; Patients receive oral exemestane once daily	Drug: Exemestane; Exemestane
Active Comparator: Arm II; Patients receive exemestane as in arm I and oral bicalutamide once daily	Drug: Exemestane+bicalutamide; Exemestane as in arm I and oral bicalutamide once daily

Collaborators and Investigators

• Sponsor: Swiss Group for Clinical Cancer Research
• Investigators: Study Chair: Marco Bonomo, MD, Ospedale Beata Vergine

Study record dates

Study Major Dates

• Study Start: August 1, 2001
• Primary Completion (Actual): June 1, 2002
• Study Completion (Actual): June 1, 2002

Study Registration Dates

• First Submitted: March 8, 2002
• First Submitted That Met QC Criteria: June 30, 2003
• First Posted (Estimate): July 1, 2003

Study Record Updates

• Last Update Posted (Estimate): May 15, 2012
• Last Update Submitted That Met QC Criteria: May 14, 2012
• Last Verified: May 1, 2012

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; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Androgen Antagonists; Bicalutamide; Exemestane
• Other Study ID Numbers: SAKK 09/01; EU-20139