R-Flurbiprofen in Treating Patients With Localized Prostate Cancer at Risk of Recurrence

Phase IIB, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Assess the Safety and Efficacy of MPC-7869 in Delaying the Systemic Progression of Prostate Cancer in Patients With Intermediate to High Risk of Recurrence With Rising PSA Levels After Prostatectomy, Prostatectomy and Radiotherapy or Radiotherapy Alone for Localized Disease

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. R-flurbiprofen may be effective in delaying the recurrence of localized prostate cancer.

PURPOSE: Randomized phase II trial to study the effectiveness of R-flurbiprofen in treating patients who have localized prostate cancer at risk of recurrence following radiation therapy and/or prostatectomy.

Study Overview

• Status: Unknown
• Conditions: Prostate Cancer
• Intervention / Treatment: Procedure: adjuvant therapy; Drug: tarenflurbil

Detailed Description

OBJECTIVES:

• Determine the effect of R-flurbiprofen on time to systemic disease progression evaluated over a minimum of 3 years in patients with localized adenocarcinoma of the prostate with an intermediate or high risk of recurrence and rising prostate-specific antigen (PSA) levels after radiotherapy alone, prostatectomy alone, or both radiotherapy and prostatectomy.
• Determine the effect of this drug on the change in serum PSA levels over time prior to androgen-deprivation therapy (ADT) in these patients.
• Determine the effect of this drug on the time of initiation of ADT in these patients.
• Determine the effect of this drug on the number of patients requiring ADT.
• Determine the safety of this drug in these patients.
• Determine the population pharmacokinetics of R-flurbiprofen and bioinversion of R-ToS in this patient population.
• Determine the number of patients with systemic disease progression at the end of the study.
• Determine the time to clinical disease progression in patients treated with this drug.
• Determine the time to prostate cancer-related mortality and time to all cause mortality in patients treated with this drug.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to risk of recurrence based on Gleason score at diagnosis (5-7 vs 8-10). Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive oral low-dose R-flurbiprofen twice daily.
• Arm II: Patients receive oral high-dose R-flurbiprofen twice daily.
• Arm III: Patients receive oral placebo twice daily. In all arms, treatment continues for up to 5.5 years (66 months) in the absence of disease progression or unacceptable toxicity. Patients who demonstrate increased prostate-specific antigen without objective disease progression and require androgen-deprivation therapy (ADT) continue receiving R-flurbiprofen. Patients who develop local recurrence or systemic disease may withdraw from study and receive additional therapy off study.

PROJECTED ACCRUAL: Approximately 390 patients (130 per treatment arm) will be accrued for this study within 3 years.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Homewood, Alabama, United States, 35209
      • Urology Centers Of Alabama
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Alaska Clinical Research Center, LLC
  • California
    • Fresno, California, United States, 93720
      • Urology Associates of Central California
    • Laguna Hills, California, United States, 92653
      • Orange County Urology Associates
    • Laguna Hills, California, United States, 92653
      • South Orange County Hematology-Oncology Associates
    • Loma Linda, California, United States, 92354
      • Loma Linda University Cancer Institute at Loma Linda University Medical Center
    • Long Beach, California, United States, 90806
      • Atlantic Urology Medical Group
    • Los Angeles, California, United States, 90095-7187
      • Jonsson Comprehensive Cancer Center, UCLA
    • San Diego, California, United States, 92101
      • San Diego Urological Medical Group
    • San Luis Obispo, California, United States, 93401
      • Coastal Medical Research Group, Incorporated
  • Colorado
    • Denver, Colorado, United States, 80210
      • Urology Associates - Research
  • District of Columbia
    • Washington, District of Columbia, United States, 20307-5001
      • Walter Reed Army Medical Center
  • Florida
    • Aventura, Florida, United States, 33180
      • South Florida Medical Research
    • Boca Raton, Florida, United States, 33428
      • Lynn Regional Cancer Center West
    • Fort Myers, Florida, United States, 33901-8082
      • 21st Century Oncology - Fort Myers
    • Ocala, Florida, United States, 34471
      • UroSearch - Ocala
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Rice, Lake and Harper Urology, LLC
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83814
      • North Idaho Urology
  • Illinois
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital Cancer Care Institute
    • Decatur, Illinois, United States, 62526
      • Cancer Care Specialists of Central Illinois, S.C. - Decatur
    • Evanston, Illinois, United States, 60201-1781
      • Evanston Northwestern Health Care - Evanston Hospital
  • Indiana
    • Fort Wayne, Indiana, United States, 46825-1675
      • Northeast Indiana Research, LLC
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Cancer Center at Lexington Clinic
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
      • Regional Urology, L.L.C.
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • St. Agnes Cancer Center
    • Greenbelt, Maryland, United States, 20770
      • Drs. Werner, Murdock and Francis, P.A., Urology Associates
  • Michigan
    • St. Joseph, Michigan, United States, 49085
      • Lakeside Urology, P.C.
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Mallinckrodt Institute of Radiology
  • Nevada
    • Las Vegas, Nevada, United States, 89109
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08648
      • Lawrenceville Urology
    • Voorhees, New Jersey, United States, 08043
      • Center for Urologic Care
  • New York
    • Albany, New York, United States, 12208
      • Veterans Affairs Medical Center - Albany
    • Garden City, New York, United States, 11530
      • AccuMed Research Associates
    • Staten Island, New York, United States, 10305
      • Staten Island Urologic Oncology
  • North Carolina
    • Greensboro, North Carolina, United States, 27401
      • Urology Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0589
      • Charles M. Barrett Cancer Center at University Hospital
    • Cleveland, Ohio, United States, 44106-5046
      • Ireland Cancer Center
    • Columbus, Ohio, United States, 43222
      • Urological Associates, Incorporated
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Oregon Urology Specialists
  • Pennsylvania
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Center for Urologic Care
    • Lancaster, Pennsylvania, United States, 17604
      • Urological Associates of Lancaster, Ltd.
    • West Reading, Pennsylvania, United States, 19611
      • Center of Urologic Care of Berks County
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
    • Providence, Rhode Island, United States, 02904
      • University Urological Research Institute
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Grand Strand Urology LLP
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee - Graduate School of Medicine
    • Nashville, Tennessee, United States, 37209
      • Urology Associates
  • Texas
    • Arlington, Texas, United States, 76012
      • Urology Associates of North Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Dallas, Texas, United States, 75231
      • Urology Clinics of North Texas
    • Dallas, Texas, United States, 75390-9110
      • Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
    • San Antonio, Texas, United States, 78229
      • Urology Consultants, P.A.
    • Temple, Texas, United States, 76508
      • Center for Cancer Prevention and Care at Scott and White Clinic
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Salt Lake Research
  • Vermont
    • Burlington, Vermont, United States, 05405-0075
      • Vermont Cancer Center at University of Vermont
  • Washington
    • Seattle, Washington, United States, 98133
      • Northwest Hospital and Medical Center
    • Seattle, Washington, United States, 98166
      • Highline Hospital Campus
  • Wisconsin
    • Madison, Wisconsin, United States, 53715
      • University of Wisconsin Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed localized adenocarcinoma of the prostate (from a pre-operative core biopsy, surgical specimen, or post-therapy core biopsy)
• Gleason score 5-10 at diagnosis (the highest score is used if multiple scores are available)

• Must have undergone 1 of the following curative treatment strategies:

  • Radical prostatectomy

    • Not a candidate for radiotherapy
  • Radical prostatectomy followed by radiotherapy at the time of surgery or any time thereafter
  • Radiotherapy of the prostate and/or surrounding structures by external beam radiotherapy (EBRT), brachytherapy (BT), or a combination of EBRT and BT
• Must have 3 consecutive rising prostate-specific antigen (PSA) measurements OR meets slope criteria

• Biochemical failure, meeting 1 of the following criteria:

  • PSA at least 0.2 ng/mL post radical prostatectomy
  • PSA greater than 1.5 ng/mL after radiotherapy or appropriate calculated slope
• Testosterone at least 100 ng/mL
• No rise in PSA with concurrent clinically active prostatitis
• No metastatic prostate cancer
• PSA no greater than 20.0 ng/mL

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• Not specified

Hematopoietic

• WBC at least 2,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10 g/dL

Hepatic

• Bilirubin no greater than 1.5 mg/dL
• AST or ALT no greater than 2 times upper limit of normal

Renal

• Creatinine no greater than 2.0 mg/dL

Cardiovascular

• No uncontrolled cardiac conditions
• No New York Heart Association class III or IV heart disease

Gastrointestinal

• No active ulcer disease diagnosed within the past 3 months
• No upper gastrointestinal bleed requiring a transfusion within the past 3 years
• No non-steroidal anti-inflammatory drug (NSAID)-associated ulcers within the past 5 years

Other

• No known hypersensitivity to NSAIDs, including COX-2-specific inhibitors (e.g., celecoxib or rofecoxib)
• No other malignancy within the past 5 years except basal cell or squamous cell skin cancer
• No active systemic infections
• No other serious uncontrolled medical condition
• No dementia or altered mental status

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent biologic therapy

Chemotherapy

• More than 5 years since prior cytotoxic chemotherapy for other malignant disease
• No prior cytotoxic chemotherapy for prostate cancer
• No concurrent chemotherapy

Endocrine therapy

• More than 9 months since prior androgen-deprivation therapy other than as cytoreductive therapy (neoadjuvantly or adjuvantly for less than 9 months) with the intent to cure
• More than 3 months since prior cyproterone, finasteride, diethylstilbestrol, megestrol, or other hormonally active (antiandrogen or antiprostate) therapies

Radiotherapy

• See Disease Characteristics
• No prior strontium chloride Sr 89, samarium Sm 153 lexidronam pentasodium, or other radioisotope materials for palliative intent or metastasis intervention
• Concurrent iodine I 125 or palladium Pd 103 for primary brachytherapy with curative intent allowed

Surgery

• See Disease Characteristics
• More than 8 weeks since prior major surgery and recovered
• No prior orchiectomy

Other

• More than 1 month since prior PC-SPES
• More than 1 month since prior investigational agents or devices (6 months for other investigational therapy for prostate cancer)
• No prior bisphosphonates (e.g., pamidronate, alendronate, or clodronate) for palliative intent or metastasis intervention
• At least 2 months since prior chronic non-steroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase-2 (COX-2)-specific inhibitors (e.g., celecoxib or rofecoxib), administered for more than 7 days per month

• No concurrent CYP2C9 inhibitor or substrates, including but not limited to the following:

  • Phenytoin
  • Fluvastatin
  • Amiodarone
  • Fluconazole
  • Acenocoumarol
  • Diclofenac
• No concurrent ketoconazole
• No concurrent antiretroviral therapy for HIV-positive patients
• Concurrent cardioprotective aspirin up to 100 mg once daily allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Masking: Double

Collaborators and Investigators

• Sponsor: Myrexis Inc.
• Investigators: Sheron B. Bass, RN, MS, Myrexis Inc.

Study record dates

Study Major Dates

• Study Start: February 1, 2002

Study Registration Dates

• First Submitted: September 6, 2002
• First Submitted That Met QC Criteria: February 5, 2003
• First Posted (Estimate): February 6, 2003

Study Record Updates

• Last Update Posted (Estimate): December 18, 2013
• Last Update Submitted That Met QC Criteria: December 17, 2013
• Last Verified: February 1, 2004

More Information

Terms related to this study

• Keywords: recurrent prostate cancer; adenocarcinoma of the prostate
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Disease Attributes; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Recurrence
• Other Study ID Numbers: CDR0000256371; MYRIAD-MPR-7869-001