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

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00045123
• Other study ID #: CDR0000256371
• Secondary ID: MYRIAD-MPR-7869-
• Status: Active, not recruiting
• Phase: Phase 2
• First received: September 6, 2002
• Last updated: December 17, 2013
• Start date: February 2002

Study information

• Verified date: February 2004
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Other known NCT identifiers

• NCT00043251

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• tarenflurbil

Procedure:
• adjuvant therapy

Locations

Country	Name	City	State
United States	Veterans Affairs Medical Center - Albany	Albany	New York
United States	Alaska Clinical Research Center, LLC	Anchorage	Alaska
United States	Urology Associates of North Texas	Arlington	Texas
United States	South Florida Medical Research	Aventura	Florida
United States	St. Agnes Cancer Center	Baltimore	Maryland
United States	Lynn Regional Cancer Center West	Boca Raton	Florida
United States	Center for Urologic Care	Bryn Mawr	Pennsylvania
United States	Vermont Cancer Center at University of Vermont	Burlington	Vermont
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Ireland Cancer Center	Cleveland	Ohio
United States	North Idaho Urology	Coeur d'Alene	Idaho
United States	Rice, Lake and Harper Urology, LLC	Columbus	Georgia
United States	Urological Associates, Incorporated	Columbus	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Urology Clinics of North Texas	Dallas	Texas
United States	Cancer Care Specialists of Central Illinois, S.C. - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	Urology Associates - Research	Denver	Colorado
United States	Oregon Urology Specialists	Eugene	Oregon
United States	Evanston Northwestern Health Care - Evanston Hospital	Evanston	Illinois
United States	21st Century Oncology - Fort Myers	Fort Myers	Florida
United States	Northeast Indiana Research, LLC	Fort Wayne	Indiana
United States	Urology Associates Of Central California	Fresno	California
United States	AccuMed Research Associates	Garden City	New York
United States	Drs. Werner, Murdock and Francis, P.A., Urology Associates	Greenbelt	Maryland
United States	Urology Center	Greensboro	North Carolina
United States	Urology Centers of Alabama	Homewood	Alabama
United States	University of Tennessee - Graduate School of Medicine	Knoxville	Tennessee
United States	Orange County Urology Associates	Laguna Hills	California
United States	South Orange County Hematology-Oncology Associates	Laguna Hills	California
United States	Urological Associates of Lancaster, Ltd.	Lancaster	Pennsylvania
United States	Lawrenceville Urology	Lawrenceville	New Jersey
United States	Cancer Center at Lexington Clinic	Lexington	Kentucky
United States	Loma Linda University Cancer Institute at Loma Linda University Medical Center	Loma Linda	California
United States	Atlantic Urology Medical Group	Long Beach	California
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	Grand Strand Urology LLP	Myrtle Beach	South Carolina
United States	Urology Associates	Nashville	Tennessee
United States	UroSearch - Ocala	Ocala	Florida
United States	Rhode Island Hospital	Providence	Rhode Island
United States	University Urological Research Institute	Providence	Rhode Island
United States	Salt Lake Research	Salt Lake City	Utah
United States	Urology Consultants, P.A.	San Antonio	Texas
United States	San Diego Urological Medical Group	San Diego	California
United States	Coastal Medical Research Group, Incorporated	San Luis Obispo	California
United States	Highline Hospital Campus	Seattle	Washington
United States	Northwest Hospital and Medical Center	Seattle	Washington
United States	Regional Urology, L.L.C.	Shreveport	Louisiana
United States	Lakeside Urology, P.C.	St. Joseph	Michigan
United States	Mallinckrodt Institute of Radiology	St. Louis	Missouri
United States	Staten Island Urologic Oncology	Staten Island	New York
United States	Center for Cancer Prevention and Care at Scott and White Clinic	Temple	Texas
United States	Center for Urologic Care	Voorhees	New Jersey
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	Center of Urologic Care of Berks County	West Reading	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Myrexis Inc.

Country where clinical trial is conducted

United States,