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Lapatinib Ditosylate in Treating Patients With a Rising PSA Indicating Recurrent Prostate Cancer

Primary Purpose

Recurrent Prostate Cancer, Stage I Prostate Cancer, Stage IIA Prostate Cancer

Status
Completed
Phase
Phase 2
Locations
United States
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: Histologically confirmed diagnosis of prostate cancer Previous treatment with definitive surgery or radiation therapy Prior salvage therapy (surgery, radiation, or other local ablative procedures) is allowed if the intent was for cure No evidence of metastatic disease on physical exam, computed tomography (CT) (magnetic resonance imaging [MRI]), and bone scan Prior neoadjuvant/adjuvant hormonal or chemotherapy and investigational agents are allowed if it was last used >= 1 year prior to enrollment (no prior vaccine/immunotherapy for prostate cancer will be allowed) No therapy modulating testosterone levels (such as luteinizing-hormone releasing-hormone agonists/antagonists and antiandrogens) is permitted within 1 year prior to enrollment; agents such as 5alpha-reductase inhibitors, ketoconazole, megestrol acetate, systemic steroids, or herbal supplements are not permitted at any time during the period that the PSA values are being collected Hormone-sensitive prostate cancer as evident by a serum total testosterone level > 150 ng/dL within 4 weeks prior to registration All patients must have evidence of biochemical progression as determined by a reference PSA value followed by 2 rising PSA values, each higher than the previous value, obtained at least 6 weeks apart; all of these PSA values must be obtained at the same reference lab, and all must be done within 6 months prior to enrollment The most recent of the PSA values must be greater than 0.4 ng/ml (after prostatectomy) or greater than 1.5 ng/ml (after radiation therapy) at time of enrollment; this measurement must be obtained within 6 months prior to enrollment PSA doubling time (PSADT) must be =< 365 days Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 Leukocytes >= 3000/mm^3 Granulocytes >= 1500/mm^3 Platelet count >= 100,000/mm^3 Serum creatinine within normal institutional limits or creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal Serum total bilirubin within normal institutional limits Serum alkaline phosphatase within normal institutional limits Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamic pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x institutional upper limit of normal Cardiac ejection fraction within the institutional range of normal, as measured by echocardiogram or multi gated acquisition scan (MUGA) scan within 4 weeks prior to registration; note that baseline and on-treatment scans should be performed using the same modality and preferably at the same institution No unstable arrhythmias on electrocardiogram (ECG) are allowed (rate controlled, asymptomatic atrial fibrillation is allowed) No concomitant use of any medication classified as cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inducer or inhibitor; for patients previously treated with one of these prohibited medications, the prohibited agent needs to be discontinued, either 7 days, 14 days, or 6 months prior to the administration of the first dose of study medication Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated Normal prothrombin time (PT)/international normalized ratio (INR) within 4 weeks prior to registration Able to swallow and retain oral medication Patients with gastrointestinal (GI) tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis) will not be eligible Sexually active males are strongly advised to use an accepted and effective method of contraception Patients may not be receiving any other investigational agents or receiving concurrent anticancer therapy No history of allergic reactions attributed to compounds of similar chemical or biologic composition to GW572016 No 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 No other malignancies permitted within the past 5 years with the exception of non-melanoma skin cancer treated with curative intent

Sites / Locations

  • ECOG-ACRIN Cancer Research Group

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (lapatinib ditosylate)

Arm Description

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

Outcomes

Primary Outcome Measures

Number of Patients With PSA Response, Defined as a 50% or Greater Decline in the Serum PSA Level
PSA response is defined as either complete response (CR) or partial response (PR) observed at any time during the entire measurement time period. CR: In patients treated with prior radical prostatectomy, a PSA < 0.2 ng/mL confirmed by a repeat PSA at least one month apart was considered a complete biochemical response. In patients treated with radiation therapy only, a PSA < 1 ng/mL on three separate occasions taken at least one month apart was considered a complete biochemical response. PR: A reduction in PSA by > 50% from baseline, confirmed by repeat PSA 1 month later.

Secondary Outcome Measures

The Change in PSA Slope With GW572016 (Lapatinib)
PSA was evaluated every cycle while on treatment. PSA test results show the level of PSA detected in the blood. These results were reported as nanograms of PSA per milliliter (ng/mL) of blood. PSA slope is the change in PSA level over time. A sharp rise in the PSA level raises the suspicion of cancer and may indicate a fast-growing cancer.
Progression-free Survival Rate at 2 Years
Proportion of patients who are living with a disease that does not get worse at 2 years from registration based on Kaplan-Meier method.
Relationship Between Progression-free Survival and EGFR Expression Levels
The association between EGFR (epidermal growth factor receptor) expression levels and the length of time during and after treatment in which a patient is living with a disease that does not get worse.

Full Information

First Posted
February 7, 2005
Last Updated
September 19, 2014
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00103194
Brief Title
Lapatinib Ditosylate in Treating Patients With a Rising PSA Indicating Recurrent Prostate Cancer
Official Title
Phase II Trial of GW572016 in Patients With Recurrent Prostate Cancer as Evident by a Rising PSA
Study Type
Interventional

2. Study Status

Record Verification Date
June 2014
Overall Recruitment Status
Completed
Study Start Date
September 2005 (undefined)
Primary Completion Date
June 2013 (Actual)
Study Completion Date
June 2013 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II trial studies how well lapatinib ditosylate works in treating patients with a rising prostate-specific antigen (PSA), a protein made by the prostate gland, indicating that prostate cancer has come back after previous treatment. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and may delay or prevent the progression of prostate cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the percentage of patients with hormone sensitive prostate cancer who experience > 50% decline in serum PSA during treatment with GW572016 (lapatinib ditosylate). SECONDARY OBJECTIVES: I. To evaluate the duration of PSA decline. II. To characterize the change in PSA slope with GW572016. III. To characterize the safety and tolerability of GW572016 in this patient population. IV. To estimate the time to progression (TTP) and progression-free survival at 2 years (from start of therapy). V. To evaluate the correlation of epidermal growth factor receptor (EGFR) expression/signaling (from available prostate biopsy specimens or prostatectomy blocks) and its relationship to change in PSA in patients treated with GW572016. OUTLINE: Patients receive lapatinib ditosylate orally (PO) daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, or every year if patient is 5-10 years from study entry for 10 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Prostate Cancer, Stage I Prostate Cancer, Stage IIA Prostate Cancer, Stage IIB Prostate Cancer, Stage III 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
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (lapatinib ditosylate)
Arm Type
Experimental
Arm Description
Patients receive lapatinib ditosylate PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
lapatinib ditosylate
Other Intervention Name(s)
GSK572016, GW-572016, GW2016, Lapatinib, Tykerb
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Number of Patients With PSA Response, Defined as a 50% or Greater Decline in the Serum PSA Level
Description
PSA response is defined as either complete response (CR) or partial response (PR) observed at any time during the entire measurement time period. CR: In patients treated with prior radical prostatectomy, a PSA < 0.2 ng/mL confirmed by a repeat PSA at least one month apart was considered a complete biochemical response. In patients treated with radiation therapy only, a PSA < 1 ng/mL on three separate occasions taken at least one month apart was considered a complete biochemical response. PR: A reduction in PSA by > 50% from baseline, confirmed by repeat PSA 1 month later.
Time Frame
Assessed every cycle while on treatment; after being off-treatment, assessed every 3 months for 2 years, then every 6 months for 3 years, then annually for 5 years
Secondary Outcome Measure Information:
Title
The Change in PSA Slope With GW572016 (Lapatinib)
Description
PSA was evaluated every cycle while on treatment. PSA test results show the level of PSA detected in the blood. These results were reported as nanograms of PSA per milliliter (ng/mL) of blood. PSA slope is the change in PSA level over time. A sharp rise in the PSA level raises the suspicion of cancer and may indicate a fast-growing cancer.
Time Frame
Assessed every cycle while on treatment; after being off-treatment, assessed every 3 months for 2 years, then every 6 months for 3 years, then annually, for 5 years
Title
Progression-free Survival Rate at 2 Years
Description
Proportion of patients who are living with a disease that does not get worse at 2 years from registration based on Kaplan-Meier method.
Time Frame
Assessed every cycle while on treatment; after being off-treatment, assessed every 3 months for 2 years, then every 6 months for 3 years, then annually for 5 years
Title
Relationship Between Progression-free Survival and EGFR Expression Levels
Description
The association between EGFR (epidermal growth factor receptor) expression levels and the length of time during and after treatment in which a patient is living with a disease that does not get worse.
Time Frame
Assessed every cycle while on treatment; after being off-treatment, assessed every 3 months for 2 years, then every 6 months for 3 years, then annually for 5 years

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed diagnosis of prostate cancer Previous treatment with definitive surgery or radiation therapy Prior salvage therapy (surgery, radiation, or other local ablative procedures) is allowed if the intent was for cure No evidence of metastatic disease on physical exam, computed tomography (CT) (magnetic resonance imaging [MRI]), and bone scan Prior neoadjuvant/adjuvant hormonal or chemotherapy and investigational agents are allowed if it was last used >= 1 year prior to enrollment (no prior vaccine/immunotherapy for prostate cancer will be allowed) No therapy modulating testosterone levels (such as luteinizing-hormone releasing-hormone agonists/antagonists and antiandrogens) is permitted within 1 year prior to enrollment; agents such as 5alpha-reductase inhibitors, ketoconazole, megestrol acetate, systemic steroids, or herbal supplements are not permitted at any time during the period that the PSA values are being collected Hormone-sensitive prostate cancer as evident by a serum total testosterone level > 150 ng/dL within 4 weeks prior to registration All patients must have evidence of biochemical progression as determined by a reference PSA value followed by 2 rising PSA values, each higher than the previous value, obtained at least 6 weeks apart; all of these PSA values must be obtained at the same reference lab, and all must be done within 6 months prior to enrollment The most recent of the PSA values must be greater than 0.4 ng/ml (after prostatectomy) or greater than 1.5 ng/ml (after radiation therapy) at time of enrollment; this measurement must be obtained within 6 months prior to enrollment PSA doubling time (PSADT) must be =< 365 days Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 Leukocytes >= 3000/mm^3 Granulocytes >= 1500/mm^3 Platelet count >= 100,000/mm^3 Serum creatinine within normal institutional limits or creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal Serum total bilirubin within normal institutional limits Serum alkaline phosphatase within normal institutional limits Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamic pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x institutional upper limit of normal Cardiac ejection fraction within the institutional range of normal, as measured by echocardiogram or multi gated acquisition scan (MUGA) scan within 4 weeks prior to registration; note that baseline and on-treatment scans should be performed using the same modality and preferably at the same institution No unstable arrhythmias on electrocardiogram (ECG) are allowed (rate controlled, asymptomatic atrial fibrillation is allowed) No concomitant use of any medication classified as cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inducer or inhibitor; for patients previously treated with one of these prohibited medications, the prohibited agent needs to be discontinued, either 7 days, 14 days, or 6 months prior to the administration of the first dose of study medication Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated Normal prothrombin time (PT)/international normalized ratio (INR) within 4 weeks prior to registration Able to swallow and retain oral medication Patients with gastrointestinal (GI) tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis) will not be eligible Sexually active males are strongly advised to use an accepted and effective method of contraception Patients may not be receiving any other investigational agents or receiving concurrent anticancer therapy No history of allergic reactions attributed to compounds of similar chemical or biologic composition to GW572016 No 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 No other malignancies permitted within the past 5 years with the exception of non-melanoma skin cancer treated with curative intent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Glenn Liu
Organizational Affiliation
ECOG-ACRIN Cancer Research Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
ECOG-ACRIN Cancer Research Group
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19103
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21784672
Citation
Liu G, Chen YH, Kolesar J, Huang W, Dipaola R, Pins M, Carducci M, Stein M, Bubley GJ, Wilding G. Eastern Cooperative Oncology Group Phase II Trial of lapatinib in men with biochemically relapsed, androgen dependent prostate cancer. Urol Oncol. 2013 Feb;31(2):211-8. doi: 10.1016/j.urolonc.2011.01.002. Epub 2011 Jul 23.
Results Reference
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Lapatinib Ditosylate in Treating Patients With a Rising PSA Indicating Recurrent Prostate Cancer

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