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Lapatinib in Treating Patients With Recurrent or Metastatic Prostate Cancer

Primary Purpose

Recurrent Prostate Cancer, Stage IV Prostate Cancer

Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
lapatinib ditosylate
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Prostate Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria: Patients must have histologically or cytologically confirmed prostate cancer that is recurrent after local therapy, and/or metastatic carcinoma confirmed to be of prostate origin Patients must have recurrent and/or metastatic disease that is progressive and not amenable to surgery or curative radiotherapy; progressive disease is defined as: Three consecutive rising PSAs, at least 4 weeks apart with an absolute increase of at least 0.5 PSA doubling time of less than one year PSA > 2.0 For recurrent disease following local therapy (surgery/radiation), prior neoadjuvant or adjuvant hormones are allowed if completed more than a year prior to study entry; for metastatic disease, no prior medical therapy (hormonal, corticosteroid, chemotherapy) is allowed Life expectancy of greater than 12 weeks ECOG performance status 0,1, or 2 Leukocytes >= 3,000/uL Absolute neutrophil count >= 1,500/uL Platelets >= 100,000/uL Total bilirubin within normal institutional limits AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal Creatinine within normal institutional limits or creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram or MUGA scan; note that baseline and on treatment scans should be performed using the same modality and preferably at the same institution Must be willing and able to undergo tumor biopsy once before (if no previous specimen available) and once during investigational therapy if there are lesions accessible for biopsy for correlative studies; in cases where there is a medical contraindication to tumor biopsy, exception may be granted only upon discussion with the principal investigator Eligibility of patients receiving medications or substances known to affect, or with the potential to affect the activity or pharmacokinetics of GW572016 will be determined following review of their use by the principal investigator Patients requiring oral anticoagulants (coumadin, warfarin) are eligible provided there is increased vigilance with respect to monitoring INR Women of child-bearing potential and 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; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Ability to understand and the willingness to sign a written informed consent document Able to swallow and retain oral medication Exclusion Criteria: Prior treatment: Patients who have had prior chemotherapy for prostate cancer Patients who have been on androgen ablative therapies within the last year Patients receiving radiotherapy to the prostate less than 6 weeks prior to study entry Patients who have had prior treatment with EGFR targeting therapies Patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier Patients may not be receiving any other investigational agents or receiving concurrent anticancer therapy Patients with a history of other active malignancy in the past 5 years (with the exception of adequately treated non-melanomatous skin cancers) are excluded History of allergic reactions attributed to compounds of similar chemical or biological composition to GW572016 Uncontrolled intercurrent 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 Patients with cardiac ejection fraction, not within the institutional range of normal as measured by echocardiogram or MUGA scan at baseline 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 inducer or inhibitor

Sites / Locations

  • Princess Margaret Hospital Phase 2 Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (lapatinib ditosylate)

Arm Description

Patients receive oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.

Outcomes

Primary Outcome Measures

PSA response rate defined as at least a 50% fall in PSA from baseline confirmed by a second PSA 4 weeks later

Secondary Outcome Measures

Objective tumor response
Potential association between variables will be measured using Pearson correlation coefficients, chi-square tests, one- or two-sample t-tests or logistic regression analyses as appropriate. Non-parametric tests such as Spearman correlation coefficients, Fisher's exact tests and Wilcoxon tests may be substituted if necessary. Ninety-five percent confidence intervals will be constructed and selected results will be illustrated using figures and plots.
Duration of PSA response
Potential association between variables will be measured using Pearson correlation coefficients, chi-square tests, one- or two-sample t-tests or logistic regression analyses as appropriate. Non-parametric tests such as Spearman correlation coefficients, Fisher's exact tests and Wilcoxon tests may be substituted if necessary. Ninety-five percent confidence intervals will be constructed and selected results will be illustrated using figures and plots.
Rate and duration of stable disease
Potential association between variables will be measured using Pearson correlation coefficients, chi-square tests, one- or two-sample t-tests or logistic regression analyses as appropriate. Non-parametric tests such as Spearman correlation coefficients, Fisher's exact tests and Wilcoxon tests may be substituted if necessary. Ninety-five percent confidence intervals will be constructed and selected results will be illustrated using figures and plots.
Progression-free survival
Will be computed using the Kaplan-Meier method.
Overall survival
Will be computed using the Kaplan-Meier method.
Safety and tolerability assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest.

Full Information

First Posted
November 5, 2004
Last Updated
May 7, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00095667
Brief Title
Lapatinib in Treating Patients With Recurrent or Metastatic Prostate Cancer
Official Title
A Phase 2 Study of GW572016 in Hormone Naive Recurrent or Metastatic Hormone Sensitive Prostate Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
May 2013
Overall Recruitment Status
Completed
Study Start Date
November 2004 (undefined)
Primary Completion Date
November 2007 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
Lapatinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Phase II trial to study the effectiveness of lapatinib in treating patients who have recurrent or metastatic prostate cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the antitumor activity of GW572016 in hormone naïve, recurrent and/or metastatic hormone sensitive prostate cancer using PSA response rate. SECONDARY OBJECTIVES: I. To estimate objective tumor response in patients with measurable disease. II. To determine the duration of PSA response, rate and duration of stable disease, progression-free, median and overall survival rates of GW572016 in recurrent and/or metastatic prostate cancer. III. To document the safety and tolerability of GW572016 in these patient populations. TERTIARY OBJECTIVES: I. To investigate if differences in baseline levels of EGFR and/or erbB2 expression, and receptor phosphorylation status in tumor specimens predict outcome to therapy. II. To investigate if the inhibitory effects of GW572016 on EGFR and/or erbB2 pathway activation in tumor specimens correlates with clinical outcome. OUTLINE: This is a nonrandomized, open-label, multicenter study. Patients receive oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients are followed for survival. PROJECTED ACCRUAL: A total of 21-41 patients will be accrued for this study within 11.7 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Prostate Cancer, Stage IV Prostate Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
41 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (lapatinib ditosylate)
Arm Type
Experimental
Arm Description
Patients receive oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.
Intervention Type
Drug
Intervention Name(s)
lapatinib ditosylate
Other Intervention Name(s)
GSK572016, GW-572016, GW2016, Lapatinib, Tykerb
Intervention Description
Given orally
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
PSA response rate defined as at least a 50% fall in PSA from baseline confirmed by a second PSA 4 weeks later
Time Frame
Up to 3 years
Secondary Outcome Measure Information:
Title
Objective tumor response
Description
Potential association between variables will be measured using Pearson correlation coefficients, chi-square tests, one- or two-sample t-tests or logistic regression analyses as appropriate. Non-parametric tests such as Spearman correlation coefficients, Fisher's exact tests and Wilcoxon tests may be substituted if necessary. Ninety-five percent confidence intervals will be constructed and selected results will be illustrated using figures and plots.
Time Frame
Up to 3 years
Title
Duration of PSA response
Description
Potential association between variables will be measured using Pearson correlation coefficients, chi-square tests, one- or two-sample t-tests or logistic regression analyses as appropriate. Non-parametric tests such as Spearman correlation coefficients, Fisher's exact tests and Wilcoxon tests may be substituted if necessary. Ninety-five percent confidence intervals will be constructed and selected results will be illustrated using figures and plots.
Time Frame
Up to 3 years
Title
Rate and duration of stable disease
Description
Potential association between variables will be measured using Pearson correlation coefficients, chi-square tests, one- or two-sample t-tests or logistic regression analyses as appropriate. Non-parametric tests such as Spearman correlation coefficients, Fisher's exact tests and Wilcoxon tests may be substituted if necessary. Ninety-five percent confidence intervals will be constructed and selected results will be illustrated using figures and plots.
Time Frame
From the start of the treatment until the criteria for progression are met, assessed up to 3 years
Title
Progression-free survival
Description
Will be computed using the Kaplan-Meier method.
Time Frame
From start of treatment to time criteria are met for disease progression, assessed up to 3 years
Title
Overall survival
Description
Will be computed using the Kaplan-Meier method.
Time Frame
Up to 3 years
Title
Safety and tolerability assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Description
Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest.
Time Frame
Up to 3 years

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have histologically or cytologically confirmed prostate cancer that is recurrent after local therapy, and/or metastatic carcinoma confirmed to be of prostate origin Patients must have recurrent and/or metastatic disease that is progressive and not amenable to surgery or curative radiotherapy; progressive disease is defined as: Three consecutive rising PSAs, at least 4 weeks apart with an absolute increase of at least 0.5 PSA doubling time of less than one year PSA > 2.0 For recurrent disease following local therapy (surgery/radiation), prior neoadjuvant or adjuvant hormones are allowed if completed more than a year prior to study entry; for metastatic disease, no prior medical therapy (hormonal, corticosteroid, chemotherapy) is allowed Life expectancy of greater than 12 weeks ECOG performance status 0,1, or 2 Leukocytes >= 3,000/uL Absolute neutrophil count >= 1,500/uL Platelets >= 100,000/uL Total bilirubin within normal institutional limits AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal Creatinine within normal institutional limits or creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram or MUGA scan; note that baseline and on treatment scans should be performed using the same modality and preferably at the same institution Must be willing and able to undergo tumor biopsy once before (if no previous specimen available) and once during investigational therapy if there are lesions accessible for biopsy for correlative studies; in cases where there is a medical contraindication to tumor biopsy, exception may be granted only upon discussion with the principal investigator Eligibility of patients receiving medications or substances known to affect, or with the potential to affect the activity or pharmacokinetics of GW572016 will be determined following review of their use by the principal investigator Patients requiring oral anticoagulants (coumadin, warfarin) are eligible provided there is increased vigilance with respect to monitoring INR Women of child-bearing potential and 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; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Ability to understand and the willingness to sign a written informed consent document Able to swallow and retain oral medication Exclusion Criteria: Prior treatment: Patients who have had prior chemotherapy for prostate cancer Patients who have been on androgen ablative therapies within the last year Patients receiving radiotherapy to the prostate less than 6 weeks prior to study entry Patients who have had prior treatment with EGFR targeting therapies Patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier Patients may not be receiving any other investigational agents or receiving concurrent anticancer therapy Patients with a history of other active malignancy in the past 5 years (with the exception of adequately treated non-melanomatous skin cancers) are excluded History of allergic reactions attributed to compounds of similar chemical or biological composition to GW572016 Uncontrolled intercurrent 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 Patients with cardiac ejection fraction, not within the institutional range of normal as measured by echocardiogram or MUGA scan at baseline 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 inducer or inhibitor
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Trachtenberg
Organizational Affiliation
Princess Margaret Hospital Phase 2 Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Princess Margaret Hospital Phase 2 Consortium
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada

12. IPD Sharing Statement

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Lapatinib in Treating Patients With Recurrent or Metastatic Prostate Cancer

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