castrate-resistant prostate cancer MedDRA version: 20.0 Level: LLT Classification code 10076506 Term: Castration-resistant prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10060862 Term: Prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: atorvastatin
Pharmaceutical Form:
INN or Proposed INN: ATORVASTATIN
CAS Number: 134523-00-5
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 10-80
Pr
Sponsors
Gustave Roussy
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: • Histologically confirmed adenocarcinoma of the prostate and no curative local therapy considered possible • Age = 18 years, life expectancy of at least 6 months • CRPC defined as tumor progression (PSA increase on at least 2 separate values separated by at least 1 week or progression on imaging) while on Androgen Deprivation Therapy (orchiectomy, LHRH agonist or –antagonist) with documented serum testosterone levels = 1.7 nmol/L (= 0.50 ng/mL). Ongoing concurrent use of LHRH agonist or antagonist is required if the patient has not been surgically castrated • Presence (M1) or absence (M0) of metastases on imaging • Performance status 0, 1 or 2 • No previous use of life- prolonging treatments for CRPC (including abiraterone, enzalutamide, radium-223, docetaxel, cabazitaxel, and sipuleucel-T). The use of these agents together with Androgen Deprivation Therapy (ADT) for castrate-sensitive disease is allowed. • Adequate renal function within 30 days prior to registration: calculated creatinine clearance = 50 mL/min, according to the formula of Cockcroft-Gault and adequate liver function with levels of AST and ALT = 3xULN and no signs for cholestasis. • Participation in other clinical trials is allowed except for trials with the same primary endpoint, i.e. OS • Patient authorized to participate to a clinical trial by specific country regulation (eg patient affiliated to a social security system or beneficiary of the same) • Information delivered to patient and informed consent form signed by the patient. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 210 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1000
Exclusion criteria
Exclusion criteria: • Previous localised malignancy within 2 years with the exception of localized non-melanoma skin cancer and Ta or Tis bladder cancer (patients with asymptomatic Chronic Lymphoïd Leukemia can be included) • Previous metastatic malignancy within 5 years • Patient currently taking daily acetylsalicylic acid or a daily statin within the last 6 months • Patients with active liver disease (hepatitis B or C, cirrhosis) or unexplained persistent elevations of serum transaminases exceeding 3 times the upper limit of normal or cholestasis . Patients with excessive alcohol intake or history of a relevant liver disease • Known hypersensitivity or intolerance to acetylsalicylic acid or atorvastatin or hypersensitivity to any of its components • Contra-indication to acetylsalicylic acid or atorvastatin according to label, including known high-risk for haemorrhage, • History of or active myopathy or significantly elevated (> 5 times ULN) CK levels • History of recent stroke or transient ischemic attack (TIA). • Any concomitant drugs contraindicated for use with the trial drugs according to the product information (e.g. Fucidic acid, potent inhibitors of CYP3A4 or transport proteins: ciclosporine, telithromycin, clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, itraconazole, posaconazole and HIV protease inhibitors including ritonavir, lopinavir, atazanavir, indinavir, darunavir, tripanavir, telaprevir, saquinavir, darunavir, fosamprenavir, boceprivir, gemfibrozil, fenofibrate, etc) • Any serious underlying medical condition (by the investigator’s judgement) which could impair the ability of the patient to participate in the trial • Patients with hereditary galactose intolerance, Lapp-lactase deficiency or Glucose-Galactose-malabsorption • Compliance with trial medical follow-up impossible due to geographic, social or psychological reasons • Psychiatric disorder precluding understanding of information about trial related topics, providing informed consent, or interfering with compliance for oral drug intake
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the benefit of acetylsalicylic acid and atorvastatin on overall survival (OS) ;Secondary Objective: To assess prostate cancer-specific survival (events including only deaths due to prostate cancer) To assess progression-free survival (including PSA progression by PCWG3 criteria (see appendix 3) (recommended) or if not by investigators assessment) To assess radiographic progression-free survival (progression defined by PCWG3 criteria (recommended)) To determine time to next anticancer treatment To describe the safety (NCI-CTCAE, Version 5.0). G1 to G5 AEs considered related to acetylsalicylic acid and/or statin will be collected in the CRF. Regarding all others AEs only G3-5 have to be collected. To describe cardio-vascular morbidity: cardiovascular hospitalization (e.g. stroke, myocardial infarction) and cardio-vascular mortality or any G3/4 cardiovascular AE To determine the changes from baseline of BMI (BMI=weight (kg)/height (m)2), body weight and waist measure under treatment and correlation with OS ;Primary end point(s): Overall survival (OS). OS will be calculated from the date of randomization to the date of death (or the last follow-up date in case of censored data).;Timepoint(s) of evaluation of this end point: see above | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: -Prostate cancer- specific-survival (events including only deaths due to prostate cancer) -Progression-free survival (PFS) (including PSA progression by PCWG3 criteria (recommended) or if not, by investigator’s assessment) -Radiographic progression-free survival (progression defined by PCWG3 criteria (recommended) -Time to next anticancer treatment defined as a time from randomization date to the first new anti-cancer treatment -Baseline and Changes of BMI (BMI=weight (kg)/height (m2), body weight and waist measure under treatment Tolerance: Each patient will be regularly assessed for any potential adverse events and disease related signs and symptoms during the whole study treatment and within 30 days following the last dose. -Safety (NCI-CTC AE V5.0). G1 to G5 acetylsalicylic acid and statin-related known AEs will be collected in the CRF and regarding all the others events only G3-5 should be collected too. -Cardio-vascular morbidity: cardiovascular hospitalization (e.g. stroke, myocardial infarction) and Cardio-vascular mortality or any G3/4 cardiovascular AE ;Timepoint(s) of evaluation of this end point: see above | — |
Countries
Australia, Belgium, Denmark, Finland, France, Germany, Ireland, Italy, Spain, Switzerland
Contacts
Public ContactClinical project manager
Gustave Roussy
Outcome results
None listed