Prostate Cancer
Conditions
Keywords
adenocarcinoma of the prostate, recurrent prostate cancer, stage I prostate cancer, stage II prostate cancer, stage III prostate cancer, stage IV prostate cancer
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.
Interventions
DRUGlapatinib ditosylate
1500 mg, daily until disease progression
Sponsors
GlaxoSmithKline
UNC Lineberger Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Experiencing Decline in Prostate-specific Antigen | 4 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
| Measure | Time frame | Description |
|---|---|---|
| Time to Prostate-Specific Antigen (PSA) Progression | 4 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. |
| 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 |
Countries
United States
Participant flow
Recruitment details
Men with castration-resistant prostate cancer were recruited from 3 local institutions from 11/11/2005 to 8/29/2007.
Pre-assignment details
Of the 35 patients initially recruited, 4 were not eligible. One patient was removed in order to receive more aggressive treatment and another patient was removed due to disease progression or death prior to protocol therapy. 29 patients were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Single Arm Trial Single Arm Trial
lapatinib ditosylate: 1500 mg, daily until disease progression | 29 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Unacceptable toxicity | 2 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Single Arm Trial |
|---|---|
| Age, Continuous | 72.5 years |
| Alkaline phosphatase | 85 U/L |
| Disease Status Bone metastases only | 8 Participants |
| Disease Status Both bone and measureable disease | 7 Participants |
| Disease Status Measurable disease only | 7 Participants |
| Disease Status No metastasis | 7 Participants |
| Hemoglobin | 13 grams per deciliter |
| PSA | 21.6 ng/mL |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 26 Participants |
| Region of Enrollment United States | 29 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 29 |
| other Total, other adverse events | 29 / 29 |
| serious Total, serious adverse events | 4 / 29 |
Outcome results
Primary
Number of Patients Experiencing Decline in Prostate-specific Antigen
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.
Time frame: 4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Arm Trial | Number of Patients Experiencing Decline in Prostate-specific Antigen | 2 Participants |
Secondary
Predictive Molecular Markers of Response to Treatment With Lapatinib (GW572016)
To assess the correlation between expression of molecular markers and patient response to treatment with GW572016
Time frame: 4 years
Population: Data were not collected.
Secondary
Time to Prostate-Specific Antigen (PSA) Progression
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.
Time frame: 4 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Single Arm Trial | Time to Prostate-Specific Antigen (PSA) Progression | 29 days |