Clinical trial NCT03819101: Trial of Acetylsalicylic Acid and Atorvastatin in Patients With Castrate-resistant Prostate Cancer
Official title: A Phase III Trial of Acetylsalicylic Acid and Atorvastatin in Patients With Castrate-resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Prostate Cancer
Lead sponsor: Gustave Roussy, Cancer Campus, Grand Paris
Sponsor class: OTHER
Collaborators: name: National Cancer Institute, France
First posted: 2019-01-28
Enrollment: 1210
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: This is a 2x2 factorial randomized, multicenter, international, open phase III trial
Primary purpose: TREATMENT

Brief summary: This is a 2x2 factorial randomized, multicenter, international, open phase III trial.

The primary objective is to evaluate the benefit of acetylsalicylic acid and atorvastatin on overall survival (OS) (main endpoint) for patients with castrate-resistant prostate cancer starting first line treatment for CRPC


Eligibility 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.

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 Lymphocytic 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. Fusidic acid, potent inhibitors of CYP3A4 or transport proteins: ciclosporin, telithromycin, clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, itraconazole, posaconazole and HIV protease inhibitors including ritonavir, lopinavir, atazanavir, indinavir, darunavir, tipranavir, telaprevir, saquinavir, darunavir, fosamprenavir, boceprevir, 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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: OS will be calculated from the date of randomization to the date of death up to 15 years
Secondary outcomes:
Other outcomes:
Locations:
city: Villejuif
country: France
facility: Gustave Roussy Cancer Campus Grand Paris
state: Val De Marne
city: Besançon
country: France
facility: CHU Besançon Hopital Jean Minjoz
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Hyères
country: France
facility: Hôpital Privé Sainte Marguerite
city: Mougins
country: France
facility: Centre Azuréen de Cancérologie
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Hôpital de la Croix Saint Simon
city: Reims
country: France
facility: Institut Jean Godinot
city: Saint-Mandé
country: France
facility: Hôpital d'Instruction des Armées Bégin
city: Saint-Priest-en-Jarez
country: France
facility: Institut de Cancérologie Lucien Neuwirth
city: Suresnes
country: France
facility: Hôpital Foch
city: Vandœuvre-lès-Nancy
country: France
facility: Institut de Cancérologie de Lorraine
city: Aarau
country: Switzerland
facility: Klinik Hirslanden Aarau
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Bellinzona
country: Switzerland
facility: Bellinzona Istituto Oncologico
city: Bruderholz
country: Switzerland
facility: Kantonsspital Baselland
city: Chur
country: Switzerland
facility: Kantansspital Graubündern
city: Münsterlingen
country: Switzerland
facility: Kantonsspital Münsterlingen
city: Saint Gallen
country: Switzerland
facility: Kantonsspital St.Gallen
city: Zürich
country: Switzerland
facility: Stadtspital Triemli
Study officials:
References: