Atorvastatin Calcium and Celecoxib in Treating Patients With Rising PSA Levels After Local Therapy for Prostate Cancer

Study Overview
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Brief Summary
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RATIONALE: Atorvastatin calcium and celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving atorvastatin calcium together with celecoxib may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving atorvastatin calcium together with celecoxib works in treating patients with rising PSA levels after local therapy for prostate cancer.

Detailed Description
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OBJECTIVES: Primary To determine the effect on the biological activity, as assessed by prostate-specific antigen (PSA) response, of atorvastatin calcium and celecoxib in patients with D0 prostate cancer. Secondary To document the safety and feasibility of atorvastatin calcium and celecoxib in patients with early-stage prostate cancer. To evaluate the effects of the combination of atorvastatin calcium and celecoxib on nuclear factor-kB (NFkB), extracellular signal-regulated kinase (ERK), prostaglandin E2 (PGE2), and IL6 in peripheral blood mononuclear cells (PBMC). OUTLINE: This is a multicenter study. Patients receive oral atorvastatin calcium once daily and oral celecoxib twice daily on days 1-28. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients may undergo blood sample collection at baseline and after completion of study therapy for correlative studies. After completion of study therapy, patients are followed up every 3 months for 2 years.

Official Title
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Phase II Trial of Atorvastatin and Celecoxib in Patients With Hormone-Dependent Prostate-Specific Antigen Progression After Local Therapy for Prostate Cancer.

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: atorvastatin calcium
* Drug: celecoxib
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed prostate cancer Stage D0 disease Tumor originally diagnosed as being limited to the prostate and now having a rising prostate-specific antigen (PSA) after definitive local therapy Must have undergone local treatment via prostatectomy or radiotherapy PSA values must be ≥ 0.2 ng/mL as determined by 2 measurements, ≥ 1 month apart and ≥ 6 months after prostatectomy PSA values must be ≥ 2.0 ng/mL as determined by 2 measurements, ≥ 1 month apart and ≥ 6 months after radiotherapy The first two PSA values along with a third value must all be rising (i.e., there must be an overall rising trajectory, such that the third value cannot be lower than the first value) No metastatic disease by baseline bone scan and CT scan of the abdomen and/or pelvis PATIENT CHARACTERISTICS: Life expectancy ≥ 6 months ECOG performance status 0-2 WBC ≥ 3,500/µL ANC ≥ 1,500/µL Platelet count > 100,000/µL Hemoglobin > 10 g/dL Serum creatinine < 1.5 mg/dL OR creatinine clearance > 50 mL/min Total bilirubin normal SGOT and/or SGPT normal No serious concomitant systemic disorder that, at the discretion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study No second primary malignancy within the past 5 years except adequately treated in situ carcinoma (e.g., non-melanomatous carcinoma of the skin) or other malignancy with no evidence of recurrence No active clinically significant infection requiring antibiotics No history of coronary artery disease No myocardial infarction within the past 6 months No sulfa allergy No history of gastrointestinal bleeding PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior hormone-ablative treatment Prior neoadjuvant hormone-ablative therapy allowed provided it was completed ≥ 3 months ago More than 4 weeks since prior herbal products with hormonal activity such as soy, saw palmetto, or PC-SPES No prior or concurrent nonsteroidal anti-inflammatory drug (NSAIDS) for 7 consecutive days No COX-2 inhibitor and/or statin within the past 6 months No concurrent warfarin or any other anticoagulant, calcitriol, fibric acid derivatives, lipid-modifying doses of niacin, or strong cytochrome P450 3A4 inhibitors (e.g., cyclosporine, erythromycin, clarithromycin, and azole antifungals) or inducers (e.g., St John wort) No other concurrent anticancer agents or therapies including chemotherapy, hormonal therapy, radiotherapy, or experimental therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atorvastatin and Celecoxib<br> | Drug: atorvastatin calcium<br> <br> Drug: celecoxib<br> <br> Other: laboratory biomarker analysis<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSA Response | PSA response was defined as a decrease in slope of at least 25%, when log (PSA) is plotted vs. time. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV prostate cancer, stage III prostate cancer, recurrent prostate cancer, stage IIB prostate cancer, stage IIA prostate cancer