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

Rutgers The State University of New Jersey

Status and phase

Completed

Phase 2

Conditions

Prostate Cancer

Treatments

Drug: atorvastatin calcium

Drug: celecoxib

Other: laboratory biomarker analysis

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT01220973

0220090006 (Other Identifier)

NCI-2012-00540 (Other Identifier)

0220090006, 080811

Details and patient eligibility

About

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.

Full description

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.

Enrollment

27 patients

Sex

Male

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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