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

Phase 2
Completed
Conditions
Prostate Cancer
Interventions
Registration Number
NCT00246753
Lead Sponsor
UNC Lineberger Comprehensive Cancer Center
Brief Summary

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.

Detailed Description

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
29
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.
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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).
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Single Arm Triallapatinib ditosylateSingle Arm Trial where each patient receives GW572016 (lapatinib ditosylate) at a dose of 1500mg daily initially until disease progression or unacceptable toxicity.
Primary Outcome Measures
NameTimeMethod
Number of Patients Experiencing Decline in Prostate-specific Antigen4 years

Determine the number of patients with hormone-refractory prostate cancer who experience \> 50% decline in PSA from baseline for 2 successive measurements at least 4 weeks apart after treatment with lapatinib ditosylate.

Secondary Outcome Measures
NameTimeMethod
Predictive Molecular Markers of Response to Treatment With Lapatinib (GW572016)4 years

To assess the correlation between expression of molecular markers and patient response to treatment with GW572016

Time to Prostate-Specific Antigen (PSA) Progression4 years

Measured from start date of treatment to date of PSA progression, defined as a 25% increase above the pretreatment value or the nadir PSA (whichever is lower) and a minimum increase of 5 ng/ml, confirmed 2 or more weeks later.

Trial Locations

Locations (3)

Duke Comprehensive Cancer Center

🇺🇸

Durham, North Carolina, United States

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

🇺🇸

Chapel Hill, North Carolina, United States

Rex Cancer Center at Rex Hospital

🇺🇸

Raleigh, North Carolina, United States

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