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”

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 Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control

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.

Intervention(s) in this Clinical Trial

• Drug: R-flurbiprofen
• Procedure: adjuvant therapy

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

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Myriad Pharmaceuticals

Overall Clinical Trial Officials and Contacts

Sheron B. Bass, RN, MS  Myriad Pharmaceuticals  

Information obtained from ClinicalTrials.gov on October 15, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00045123

Study ID Number: CDR0000256371

ClinicalTrials.gov Identifier: NCT00045123

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database