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

• ClinicalTrials.gov Identifier: NCT01220973
• Recruitment Status: Completed
• First Posted: October 14, 2010
• Results First Posted: April 20, 2018
• Last Update Posted: June 8, 2018
• Sponsor: Rutgers, The State University of New Jersey
• Collaborators: Rutgers Cancer Institute of New Jersey; National Cancer Institute (NCI)
• Information provided by (Responsible Party): Susan Goodin, PharmD, Rutgers, The State University of New Jersey

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Drug: atorvastatin calcium; Drug: celecoxib; Other: laboratory biomarker analysis	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 27 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Atorvastatin and Celecoxib in Patients With Hormone-Dependent Prostate-Specific Antigen Progression After Local Therapy for Prostate Cancer.
• Study Start Date: February 2009
• Actual Primary Completion Date: November 18, 2014
• Actual Study Completion Date: November 18, 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. PSA Response [ Time Frame: 6 months ]
   PSA response was defined as a decrease in slope of at least 25%, when log (PSA) is plotted vs. time.

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, Michigan

Karmanos Cancer Center

Detroit, Michigan, United States, 48201

United States, New Jersey

Cooper Hospital

Camden, New Jersey, United States, 08103

Robert Wood Johnson University Hospital at Hamilton

Hamilton, New Jersey, United States, 08690

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States, 08903

Sponsors and Collaborators

Rutgers, The State University of New Jersey

Rutgers Cancer Institute of New Jersey

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Susan Goodin, PhD, FCCP, BCOP; Rutgers Cancer Institute of New Jersey

More Information

• Responsible Party: Susan Goodin, PharmD, Professor of Medicine, RWJMS, Rutgers, The State University of New Jersey
• ClinicalTrials.gov Identifier: NCT01220973
• Other Study ID Numbers: 0220090006, 080811; 0220090006 ( Other Identifier: IRB number ); NCI-2012-00540 ( Other Identifier: CTRP (Clinical Trails Reporting Program) )
• First Posted: October 14, 2010
• Results First Posted: April 20, 2018
• Last Update Posted: June 8, 2018
• Last Verified: May 2018

Keywords provided by Susan Goodin, PharmD, Rutgers, The State University of New Jersey:

stage IV prostate cancer; stage III prostate cancer; recurrent prostate cancer; stage IIB prostate cancer; stage IIA prostate cancer

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases; Celecoxib; Atorvastatin; Calcium; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors