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 localizedprostate cancer.

PURPOSE: Randomizedphase 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.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the prostate recurrent prostate cancer	Drug: R-flurbiprofen  Procedure: adjuvant therapy  Procedure: chemotherapy	Phase II

Further Study Details: 

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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

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

Study chairs or principal investigators

Sheron B. Bass, RN, MS,  Myriad Pharmaceuticals   

Study ID Numbers:  CDR0000256371; MYRIAD-MPR-7869-001
Record last reviewed:  June 2004
Last Updated:  October 13, 2004
Record first received:  September 6, 2002
ClinicalTrials.gov Identifier:  NCT00045123
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08