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

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

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.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: celecoxib; Drug: atorvastatin calcium

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Center
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital
    • Hamilton, New Jersey, United States, 08690
      • Robert Wood Johnson University Hospital at Hamilton
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atorvastatin and Celecoxib	Other: laboratory biomarker analysis; Drug: celecoxib; Drug: atorvastatin calcium

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Collaborators: National Cancer Institute (NCI); Rutgers Cancer Institute of New Jersey
• Investigators: Principal Investigator: Susan Goodin, PhD, FCCP, BCOP, Rutgers Cancer Institute of New Jersey

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): November 18, 2014
• Study Completion (Actual): November 18, 2014

Study Registration Dates

• First Submitted: October 13, 2010
• First Submitted That Met QC Criteria: October 13, 2010
• First Posted (Estimate): October 14, 2010

Study Record Updates

• Last Update Posted (Actual): June 8, 2018
• Last Update Submitted That Met QC Criteria: May 10, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: stage III prostate cancer; stage IV prostate cancer; recurrent prostate cancer; stage IIB prostate cancer; stage IIA prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Calcium-Regulating Hormones and Agents; Cyclooxygenase 2 Inhibitors; Atorvastatin; Celecoxib; Calcium
• Other Study ID Numbers: 0220090006, 080811; 0220090006 (Other Identifier: IRB number); NCI-2012-00540 (Other Identifier: CTRP (Clinical Trails Reporting Program))