Clinical trial NCT00045123: R-Flurbiprofen in Treating Patients With Localized Prostate Cancer at Risk of Recurrence
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
recurrent prostate cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-02-06
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility 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

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