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

April 12, 2024 updated by: Institut Claudius Regaud

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

240

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Angers, France
      • Bordeaux, France
      • Bordeaux, France
      • Créteil, France
        • Recruiting
        • CHU Henri Mondor
        • Contact:
      • Grenoble, France
        • Not yet recruiting
        • CHU Grenoble
        • Contact:
      • Lille, France
      • Marseille, France
        • Recruiting
        • Institut Paoli-Calmettes
        • Contact:
      • Paris, France
        • Recruiting
        • Hopital Europeen Georges-Pompidou
        • Contact:
      • Paris, France
        • Recruiting
        • Institut Mutualiste Montsouris
        • Contact:
      • Paris, France
        • Recruiting
        • Hopital Pitie Salpetriere
        • Contact:
      • Pierre-benite, France
      • Quint-Fonsegrives, France
        • Recruiting
        • Clinique La Croix du Sud
        • Contact:
      • Rennes, France
      • Suresnes, France
      • Toulouse, France
      • Toulouse, France
        • Recruiting
        • Institut Universitaire du Cancer Toulouse - Oncopole
        • Contact:
      • Tours, France
        • Recruiting
        • CHU Tours - Hopital Bretonneau
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental arm
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.
Active Comparator: Control arm
Other: Surgery alone
Radical prostatectomy with lymph node dissection will be performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The non-curable progression-free survival (NC-PFS) defined as the time from randomization to non-curable event.
Time Frame: 5 years for each patient
5 years for each patient

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Metastatic-Free Survival (MFS) defined as the time from randomization to the appearance of distant metastasis or death from any cause.
Time Frame: 5 years for each patient
5 years for each patient
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.
Time Frame: 5 years for each patient
5 years for each patient
Overall Survival (OS) defined as the time from randomization to death from any cause.
Time Frame: 5 years for each patient
5 years for each patient
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.
Time Frame: 5 years for each patient
5 years for each patient
Safety assessed using the NCI-CTCAE Version 5.0.
Time Frame: 3 years for each patient
3 years for each patient
Quality of life will evaluated using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire.
Time Frame: 1 year for each patient

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
Quality of life will evaluated using the 5-level EuroQol 5-Dimensional (EQ5D-5L) questionnaire.
Time Frame: 1 year for each patient
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
Quality of life will evaluated using the International Prostate Symptom Score (IPSS) questionnaire.
Time Frame: 1 year for each patient
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
Quality of life will evaluated using the International Index of Erectile Function (IIEF-15) questionnaire.
Time Frame: 1 year for each patient
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut Claudius Regaud

Collaborators

Bayer

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 10, 2023

Primary Completion (Estimated)

May 1, 2030

Study Completion (Estimated)

May 1, 2030

Study Registration Dates

First Submitted

April 12, 2023

First Submitted That Met QC Criteria

April 12, 2023

First Posted (Actual)

April 24, 2023

Study Record Updates

Last Update Posted (Estimated)

April 15, 2024

Last Update Submitted That Met QC Criteria

April 12, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 22GENH03

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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