A Phase III trial of acetylsalicylic acid and atorvastatin in patients with castrate-resistant prostate cancer (PEACE 4)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut Gustave Roussy

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12], Diseases [C] - Neoplasms [C04]

Trial duration

26 Jun 2019 → ongoing

Decision date (initial)

2026-02-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

PHRC · INCa · MOVEMBER

External identifiers

EU CT number

2023-508072-11-00

EudraCT number

2017-004639-35

ClinicalTrials.gov

NCT03819101

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Therapy, Efficacy

The primary objective is to evaluate the benefit of acetylsalicylic acid and atorvastatin on overall survival (OS) (main endpoint)

Secondary objectives 12

1. To assess prostate cancer-specific survival (events including only deaths due to prostate cancer)
2. To assess progression-free survival (including PSA progression by PCWG3 criteria (see appendix 3) (recommended) or if not by investigators assessment)
3. To assess radiographic progression-free survival (progression defined by PCWG3 criteria (recommended))
4. To determine time to next anticancer treatment
5. 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.
6. To describe cardio-vascular morbidity: cardiovascular hospitalization (e.g. stroke, myocardial infarction) and cardio-vascular mortality or any G3/4 cardiovascular AE
7. 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
8. Translational research: To correlate metabolic parameters (including baseline values of lipids and change in levels of lipids under treatment) with OS
9. Translation research To correlate low levels (
10. Translation research: To correlate LNR (Lymphocyte to Neutrophil Ratio) and CRP (C-reactive protein) with OS
11. Translation research: To validate a prognostic 3-lipid signature
12. Translation research: To assess whether treatment with atorvastatin during standard-of-care therapy for metastatic CRPC can reverse a poor prognostic circulating lipid signature and thus improve overall survival

Conditions and MedDRA coding

Castration-resistant prostate cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Histologically confirmed adenocarcinoma of the prostate and no curative local therapy considered possible
2. Age ≥ 18 years, life expectancy of at least 6 months
3. 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
4. Presence (M1) or absence (M0) of metastases on imaging
5. Performance status 0, 1 or 2
6. No previous use of life- prolonging treatments for CRPC (including abiraterone, enzalutamide, radium-223, docetaxel, cabazitaxel, and sipuleucel-T). Patients may have received up to 6 weeks of one of these first-line life-prolonging systemic treatments for their CRPC before they are included in the trial. The use of these agents together with Androgen Deprivation Therapy (ADT) for castrate-sensitive disease is allowed.
7. 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.
8. Participation in other clinical trials is allowed except for trials with the same primary endpoint, i.e. OS
9. 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)
10. Information delivered to patient and informed consent form signed by the patient.

Exclusion criteria 14

1. 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)
2. Previous metastatic malignancy within 5 years
3. Patient currently taking daily acetylsalicylic acid or a daily statin within the last 6 months
4. 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
5. Patients with excessive alcohol intake or history of a relevant liver disease
6. Known hypersensitivity or intolerance to acetylsalicylic acid or atorvastatin or hypersensitivity to any of its components
7. Contra-indication to acetylsalicylic acid or atorvastatin according to label, including known high-risk for haemorrhage,
8. History of or active myopathy or significantly elevated (> 5 times ULN) CK levels
9. History of recent stroke or transient ischemic attack (TIA).
10. 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)
11. Any serious underlying medical condition (by the investigator’s judgement) which could impair the ability of the patient to participate in the trial
12. Patients with hereditary galactose intolerance, Lapp-lactase deficiency or Glucose-Galactose-malabsorption
13. Compliance with trial medical follow-up impossible due to geographic, social or psychological reasons
14. Psychiatric disorder precluding understanding of information about trial related topics, providing informed consent, or interfering with compliance for oral drug intake

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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).

Secondary endpoints 12

1. Prostate cancer specific survival (events including only deaths due to prostate cancer)
2. Progression-Free Survival (including PSA progression by PCWG3 criteria (recommended) or if not by investigator’s assessment)
3. Radiographic Progression-Free Survival (progression defined by PCWG3 criteria)
4. Time to next anticancer treatment
5. Safety (NCI-CTC V5.0 criteria). G1 to G5 acetylsalicylic acid and statin-related known AEs and all the other events only G3-5.
6. G1 to G5 AEs considered related to acetylsalicylic acid and/or statin and about all others AEs only G3-5 have to be collected.
7. Cardio-vascular morbidity: cardiovascular hospitalization (e.g. stroke, myocardial infarction) and cardio-vascular mortality or any G3/4 cardiovascular AE
8. Changes from baseline of BMI (BMI=weight (kg)/height (m)2), body weight and waist measure under treatment
9. Translational research: Metabolic parameters (including baseline lipid profile and change in levels of lipids under treatment)
10. Translational research: Low levels of Vitamin D at baseline
11. Translational research: LNR (Lymphocyte to Neutrophil Ratio) and CRP
12. Translational research: Lipid signature

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut Gustave Roussy

Sponsor organisation

Institut Gustave Roussy

Address

114 Rue Edouard Vaillant

City

Villejuif

Postcode

94800

Country

France

Scientific contact point

Organisation

Institut Gustave Roussy

Contact name

Regulatory Affairs Officer

Public contact point

Organisation

Institut Gustave Roussy

Contact name

Regulatory Affairs Officer

Locations

2 EU/EEA countries · 40 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 36 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications