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

NCT ID: NCT00103194

Last Updated: 2014-09-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-09-30
• Study Completion Date: 2013-06-30

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.

Conditions

Recurrent Prostate Cancer; Stage I Prostate Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (lapatinib ditosylate)

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

Group Type: EXPERIMENTAL

lapatinib ditosylate

Intervention Type: DRUG

Given PO

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

lapatinib ditosylate

Given PO

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

GSK572016; GW-572016; GW2016; Lapatinib; Tykerb

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Glenn Liu

Role: PRINCIPAL_INVESTIGATOR

ECOG-ACRIN Cancer Research Group

Locations

ECOG-ACRIN Cancer Research Group

Philadelphia, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 21784672 (View on PubMed)

Other Identifiers

NCI-2014-01158

Identifier Type: REGISTRY

Identifier Source: secondary_id

E5803

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000409729

Identifier Type: -

Identifier Source: secondary_id

U10CA180820

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA021115

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2014-01158

Identifier Type: -

Identifier Source: org_study_id

NCT02154373

Identifier Type: -

Identifier Source: nct_alias