Lapatinib in Treating Patients With Prostate Cancer That Did Not Respond to Hormone Therapy

A Phase II Study of Oral Once Daily GW572016 (Lapatinib) In Patients With Hormone Refractory Prostate Cancer

RATIONALE: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well lapatinib works in treating patients with prostate cancer that did not respond to hormone therapy.

OBJECTIVES:

Primary

• Determine the proportion of patients with hormone-refractory prostate cancer who experience > 50% decline in prostate-specific antigen (PSA) after treatment with lapatinib ditosylate.

Secondary

• Determine the safety of this drug in these patients.
• Determine the time to PSA progression in patients treated with this drug.
• Determine the molecular correlates and predictive biomarkers of response in patients treated with this drug.

OUTLINE: This is a multicenter, open-label study.

Patients receive oral lapatinib ditosylate once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Serum samples are collected for biomarker analysis at baseline and every 4 weeks.

After completion of study treatment, patients are followed at 4 weeks.

Inclusion Criteria:

• Patients must have histologically confirmed diagnosis of adenocarcinoma of the prostate.
• On androgen deprivation therapy for prostate cancer (either bilateral orchiectomy or medical castration with the testosterone level of <50 ng/dl)
• Biochemical progression on androgen deprivation therapy with minimum PSA of 5 ng/ml. Progression is defined as two successive rises in PSA, measured at least one week apart. See section 4.1 for additional criteria.
• Minimum of 4-6 weeks off anti-androgen therapy (4 weeks for flutamide, 6 weeks for bicalutamide and nilutamide).
• Minimum of 4 weeks off other hormonal therapy (i.e. ketoconazole, megestrol acetate, aminoglutethimide)
• Minimum of 4 weeks from any prior radiation therapy, surgery, chemotherapy or other investigational agent.
• Patients must discontinue use of any herbal supplements prior to study initiation.
• No prior or concurrent exposure to cytotoxic chemotherapy.
• Age > 18 years.
• Life expectancy greater than 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram or multigated acquisition scan (MUGA) scan.
• Men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation since the effects of GW572016 on the developing human fetus at the recommended therapeutic dose are unknown.
• Ability to swallow and retain oral medication.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Patients who have had prior treatment with ErbB family targeting therapies.
• Patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Prior chemotherapy for prostate cancer
• Patients with known brain metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to GW572016.
• Uncontrolled inter-current 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.
• A history of a positive HIV test in the past.
• Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis).
• Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors (please refer to section 3.2.2 for a list of medications).