SUrGery with or without dARolutamide in high-risk and/or locally advanced prostate cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oncopole Claudius Regaud

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Aug 2023 → ongoing

Decision date (initial)

2023-03-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

BAYER HEALTHCARE SAS

External identifiers

EU CT number

2022-501518-67-00

ClinicalTrials.gov

NCT05826509

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

The primary objective is to determine if treatment with peri-operative darolutamide before and after surgery results in an improvement in non-curable progression-free survival (failure of cure) as compared to surgery alone in patients with high-risk and/or locally advanced prostate cancer.

Secondary objectives 4

1. - To determine if treatment with peri-operative darolutamide before and after surgery results in an improvement in other efficacy endpoints, as compared to surgery alone in patients with high-risk and/or locally advanced prostate cancer: o Metastasis-free survival (MFS) o Prostate-specific antigen (PSA) recurrence-free survival (RFS) o Overall survival (OS)
2. - To evaluate the pathological complete response rate (pCR) in the experimental arm
3. - To characterize the safety profile of treatment with peri-operative darolutamide before and after surgery in patients with high-risk and/or locally advanced prostate cancer.
4. - To evaluate patient’s quality of life.

Conditions and MedDRA coding

High-risk and/or locally advanced prostate cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. 1. Age ≥18 years
2. 2. Histologically confirmed adenocarcinoma of the prostate
3. 3. High-risk and/or locally advanced prostate cancer diagnosis defined by: One of the following criteria is sufficient to define a high-risk and/or locally advanced prostate cancer: - ISUP grade 4 or 5 on biopsies - cN1 disease in MRI or PET-Scan - T3b disease in MRI If these criteria are not being identified, two of the following criteria are necessary to define high-risk and/or locally advanced prostate cancer: - PSA value >20 ng/ml - ≥ 50% of the core of biopsies need to be positive for adenocarcinoma ISUP grade 3 - T3a disease in MRI
4. 4. No distant metastasis confirmed by imaging (i.e., MRI/CT-Scan and Bone Scintigraphy or PET-Scan)
5. 5. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-1
6. 6. Patient eligible for radical prostatectomy as per the investigator
7. 7. Adequate organ function within 28 days prior to start of treatment determined by the following central laboratory values: - Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin less than the upper limit of normal (ULN; note that in subjects with Gilbert’s syndrome, if total bilirubin is >1.5 X ULN, measure direct and indirect bilirubin. If direct bilirubin is ≤1.5 X ULN, the subject may be eligible); - Serum creatinine <1.5 mg/dL; - Platelets ≥75,000/uL, without transfusion and/or growth factors within 1 month prior to randomization; - Hemoglobin >12.0 g/dL (7.4 mmol), without transfusion and/or growth factors within 1 month prior to randomization; - Adequate renal function: creatinine clearance/eGFR within normal limits to baseline assessed as per local standard method; - Normal cardiac function according to local standard by 12-lead Electrocardiogram (ECG) (complete, standardized 12-lead recording).
8. 8. Patient able to receive darolutamide for up to 9 months, as per the investigator
9. 9. Patient able to swallow whole study drug tablets
10. 10. Life expectancy more than 5 years
11. 11. Men engaged in sexual activity with a woman of childbearing potential should accept (or female partners of men enrolled in the study who are of childbearing potential or are pregnant) to use an highly effective contraception during darolutamide treatment and at least one week after the end of the investigational product
12. 12. Signed informed consent
13. 13. Patient able to participate and willing to give informed consent prior performance of any study-related procedures and to comply with the study protocol for the duration of the study, including undergoing treatment and scheduled visits and examinations including follow up
14. 14. Patient affiliated to a Social Health Insurance in France.

Exclusion criteria 17

1. 1. Distant metastasis (clinical stage M1). Nodal disease below the iliac bifurcation (clinical stage N1) is not an exclusion.
2. 10. Gastrointestinal conditions affecting absorption
3. 11. Known or suspected contraindications or hypersensitivity to darolutamide
4. 12. Treatment with strong CYP3A4 inducers and/or P-gp inducers within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study drug
5. 13. Major surgery within 28 days before first dose of study treatment
6. 14. Any psychological, familial, geographic or social situation, according to the judgment of investigator, potentially preventing the provision of informed consent or compliance to study procedure
7. 15. Patient who has forfeited his/her freedom by administrative or legal award or who is under legal protection (curatorship and guardianship, protection of justice)
8. 16. Concurrent enrolment in another interventional therapeutic clinical study
9. 2. Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of the prostate
10. 3. Prior treatment for prostate cancer
11. 4. Castrated men (Bilateral orchiectomy or other)
12. 5. History of any pelvic radiation
13. 6. Any of the following concurrent illness within 6 months prior to first dose of study drug: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (eg., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias or New York Heart Association Class II to IV heart disease; uncomplicated deep vein thrombosis is not considered exclusionary
14. 7. Uncontrolled hypertension as indicated by a systolic blood pressure (BP) ≥ 160 mmHg or diastolic BP ≥ 100 mmHg at screening despite medical management. Participants with hypertension can enroll provided BP is stable and controlled by anti-hypertensive treatment
15. 8. HIV-positive patient with one or more of the following: Not receiving highly active antiretroviral therapy; Had a change in antiretroviral therapy within 6 months of the start of screening; Receiving antiretroviral therapy that may interfere with study drug; CD4 count <350 at screening; AIDS-defining opportunistic infection within 6 months of start of screening
16. 9. Active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction
17. 17. Patients with a history of another malignancy at high risk of recurrence within 5 years and with a concurrent malignancy requiring active treatment or having required anticancer treatment within 6 months prior to inclusion

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the non-curable progression-free survival (NC-PFS). NC-PFS is defined as the time from randomization to non-curable event. At the time of analysis, patients alive without non-curable event will be censored at the last disease assessment. Patients alive without non-curable event who started a new anticancer therapy (except salvage or adjuvant pelvic radiotherapy and long-term ADT) will be censored at the last disease assessment prior to the start of the new therapy.

Secondary endpoints 6

1. MFS is defined as the time from randomization to the appearance of distant metastasis or death from any cause (all other events will be ignored). At the time of analysis, patients alive without distant metastasis will be censored at the last disease assessment. Patients alive without distant metastasis who started a new anticancer therapy (except salvage or adjuvant pelvic radiotherapy) will be censored at the last disease assessment prior to the start of the new anticancer therapy.
2. PSA-Recurrence-Free Survival (RFS) is defined as the time from randomization to PSA recurrence according to EAU criteria or death from any cause. At the time of analysis, patients alive without PSA recurrence will be censored at the last PSA assessment. Patients alive without PSA recurrence who started a new anticancer therapy will be censored at the last PSA assessment prior to the start of the new anticancer therapy.
3. Overall Survival is defined as the time from randomization to death from any cause. At the time of analysis, patients alive will be censored at the last known alive date.
4. pathological Complete Response rate is defined as the number of patients presenting a pathological complete response (i.e., absence of residual tumor found in the surgery specimens) divided by the number of patients in the experimental arm.
5. Safety will be assessed using the NCI-CTCAE Version 5.0.
6. Quality of life will be evaluated using the following questionnaire: - Functional Assessment of Cancer Therapy-Prostate (FACT-P) - EQ5D-5L - International Prostate Symptom Score (IPSS) - International Index of Erectile Function (IIEF-15)

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oncopole Claudius Regaud

Sponsor organisation

Oncopole Claudius Regaud

Address

1 Avenue Irene Joliot Curie

City

Toulouse

Postcode

31100

Country

France

Scientific contact point

Organisation

Oncopole Claudius Regaud

Contact name

Dr. Guillaume PLOUSSARD

Public contact point

Organisation

Oncopole Claudius Regaud

Contact name

Muriel MOUNIER

Locations

1 EU/EEA country · 20 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 10 files

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

Application history

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