SUrGery With or Without dARolutamide in High-risk and/or Locally Advanced Prostate Cancer

Prostate Cancer Clinical Trial

— SUGAR  

Official title:

SUrGery With or Without dARolutamide in High-risk and/or Locally Advanced Prostate Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05826509
• Other study ID #: 22GENH03
• Status: Recruiting
• Phase: Phase 2
• Start date: August 10, 2023
• Est. completion date: May 2030

Study information

• Verified date: April 2024
• Source: Institut Claudius Regaud
• Contact: Guillaume PLOUSSARD
• Phone: 05 31 15 60 15
• Email: dr.gploussard[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase II, multicenter, randomized open-label and comparative trial designed to study the effectiveness and the safety of androgen receptor antagonist (darolutamide) combined with surgery in patients with high-risk and/or locally advanced prostate cancer.

In this trial, patients will be assigned in one of the two following treatments arms:

• Arm A (control arm): Surgery alone (radical prostatectomy with lymph node dissection)

• Arm B (experimental arm): Peri-operative darolutamide + surgery (radical prostatectomy with lymph node dissection)

A total of 240 patients will have to be randomized with 120 patients in the control arm and 120 patients in the experimental arm.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: May 2030
• Est. primary completion date: May 2030
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age =18 years

2. Histologically confirmed adenocarcinoma of the prostate

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. No distant metastasis confirmed by imaging (i.e., MRI/CT-Scan and Bone Scintigraphy or PET-Scan)

5. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-1

6. Patient eligible for radical prostatectomy as per the investigator

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. Patient able to receive darolutamide for up to 9 months as per the investigator

9. Patient able to swallow whole study drug tablets

10. Life expectancy more than 5 years

11. Men should accept (or female partners of men enrolled in the study who are of childbearing potential or are pregnant) to use an effective contraception during darolutamide treatment and at least one week after the end of the investigational product

12. Signed informed consent

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. Patient affiliated to a Social Health Insurance in France.

Exclusion Criteria:

1. Distant metastasis (clinical stage M1). Nodal disease below the iliac bifurcation (clinical stage N1) is not an exclusion.

2. Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of the prostate

3. Prior treatment for prostate cancer

4. Castrated men (Bilateral orchiectomy or other)

5. History of any pelvic radiation

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

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

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

9. Active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction

10. Gastrointestinal conditions affecting absorption

11. Known or suspected contraindications or hypersensitivity to darolutamide

12. Treatment with strong CYP3A4 inducers and P-gp inducers within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study drug

13. Major surgery within 28 days before first dose of study treatment

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

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)

16. Concurrent enrolment in another interventional therapeutic clinical study.

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Other:
• Surgery alone
Radical prostatectomy with lymph node dissection will be performed.

Drug:
• Peri-operative darolutamide + surgery.
Darolutamide: 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg; for a total duration of 9 months. Darolutamide will start at day 1. Surgery: radical prostatectomy with lymph node dissection will be performed after at least 3 months of darolutamide treatment.

Locations

Country	Name	City	State
France	Chu Angers	Angers
France	CHU Bordeaux	Bordeaux
France	Institut Bergonié	Bordeaux
France	Chu Henri Mondor	Créteil
France	CHU Grenoble	Grenoble
France	Hopital Claude Huriez	Lille
France	Institut Paoli-Calmettes	Marseille
France	Hopital Europeen Georges-Pompidou	Paris
France	Hopital Pitie Salpetriere	Paris
France	Institut Mutualiste Montsouris	Paris
France	CHU Lyon - Sud	Pierre-benite
France	Clinique La Croix Du Sud	Quint-Fonsegrives
France	CHU Rennes	Rennes
France	Hopital Foch	Suresnes
France	CHU Toulouse	Toulouse
France	Institut Universitaire Du Cancer Toulouse - Oncopole	Toulouse
France	Chu Tours - Hopital Bretonneau	Tours

Sponsors (2)

Lead Sponsor	Collaborator
Institut Claudius Regaud	Bayer

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The non-curable progression-free survival (NC-PFS) defined as the time from randomization to non-curable event.		5 years for each patient
Secondary	Metastatic-Free Survival (MFS) defined as the time from randomization to the appearance of distant metastasis or death from any cause.		5 years for each patient
Secondary	PSA-RFS (Recurrence-Free survival) defined as the time from randomization to PSA recurrence according to the European Association of Urology (EAU) criteria or death from any cause.		5 years for each patient
Secondary	Overall Survival (OS) defined as the time from randomization to death from any cause.		5 years for each patient
Secondary	pathological Complete Response (pCR) rate 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 years for each patient
Secondary	Safety assessed using the NCI-CTCAE Version 5.0.		3 years for each patient
Secondary	Quality of life will evaluated using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire.	Subscale Domains: Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, Functional Well-Being, Prostate Cancer Subscale.; Responses to questions use a five-point Likert-type scale ranging from 0 ("not at all") to 4 ("very much so").	1 year for each patient
Secondary	Quality of life will evaluated using the 5-level EuroQol 5-Dimensional (EQ5D-5L) questionnaire.	The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems.	1 year for each patient
Secondary	Quality of life will evaluated using the International Prostate Symptom Score (IPSS) questionnaire.	The I-PSS is based on the answers to seven questions concerning urinary symptoms. Each question is assigned points from 0 (never) to 5 (almost always).	1 year for each patient
Secondary	Quality of life will evaluated using the International Index of Erectile Function (IIEF-15) questionnaire.	The IIEF is a 15-item questionnaire containing five domains including erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction. Each item is rated from 0 (or 1) (Severe ED/No sexual activity) to 5 (Mild/No ED).	1 year for each patient