COACTION Trial - COmbination Androgen bloCkade in inTermediate to hIgh-risk prOstate caNcer

NCT06627530 | Active Not Recruiting Phase 4

• 1 other identifier: 001/2024
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 6

Brief Summary

A Randomized Trial of Neoadjuvant Leuprorelin, Darolutamide or Both Prior to Radical Prostatectomy for Intermediate or High-risk Prostate Cancer. Prospective, randomized, parallel group, open-label with blinded endpoint adjudication multicenter clinical trial.To assess, among patients with unfavorable intermediate to high-risk prostate cancer, whether a neoadjuvant combined treatment with leuprorelin (Leuprorelin) and darolutamide is superior to monotherapy in terms of complete or almost complete pathological response.A total of 144 patients with unfavorable intermediate to high-risk prostate cancer scheduled for radical prostatectomy with extended pelvic lymph node dissection will be randomized 1:1:1 to oral darolutamide, SC leuprorelin (Leuprorelin) or both (48 patients per arm) for 24 weeks.

Conditions

Prostate Cancer

Keywords

Prostate Cancer; Radical Prostatectomy; Darolutamide; Neoadjuvant

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with minimal residual disease

  Proportion of patients with minimal residual disease, defined as residual cancer burden (RCB) ≤ 0.25 cm3 (tumor volume ≤ 0.5 cm3 × tumor cellularity ≤ 50%) or complete pathological response, assessed by pathology of surgical specimen obtained from prostatectomy.

  Patients are expected to undergo surgery after no more than 30 days after completion of the neoadjuvant regimen therapy, which will last for 24 weeks after randomization in all 3 groups.

Secondary Outcomes (9)

• Complete biochemical response assessed by serum PSA with the rate of PSA<0,2 ng/dL

  24 weeks

• Treatment emergent adverse events and serious adverse events.

  24 weeks

• PSA levels at 3 months after prostatectomy.

  in 42 weeks

• Testosterone levels.

  in 42 weeks

• Number of positive lymph nodes.

  30 weeks

Study Arms (3)

Darolutamide + ADT leuprorelin

EXPERIMENTAL

Drug: Darolutamide Oral Tablet; Drug: leuprorelin

Darolutamide

ACTIVE COMPARATOR

Drug: Darolutamide Oral Tablet

Leuprorelin

ACTIVE COMPARATOR

Drug: leuprorelin

Interventions

Darolutamide Oral Tablet DRUG

darolutamide 600 mg PO BID for 24 weeks

Darolutamide; Darolutamide + ADT leuprorelin

leuprorelin DRUG

leuprorelin depot 22.5 mg SC every 12 weeks

Darolutamide + ADT leuprorelin; Leuprorelin

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men ≥18 years of age;
• Histologically confirmed unfavorable intermediate or high/very high risk non metastatic (by conventional imaging) prostate adenocarcinoma intended for surgery without neuroendocrine differentiation or small cell features;
• Unfavorable intermediate-risk:
• ISUP grade 3, and/or \> 50% positive biopsy cores and/or at least two intermediate-risk factors. Intermediate-risk factors:
• Clinical tumor stage T2b or T2c (MRI based);
• ISUP grade 2 or 3;
• Prostate-specific antigen (PSA) level of 10-20 ng/mL.
• High-risk or very high-risk:
• ≥cT3a (MRI based) or ISUP 4-5 or PSA\>20 ng/mL;
• cN1.
• ECOG 0-1;
• Baseline testosterone \> 230 ng/dL;
• No prior prostate cancer treatment;
• Sexually active male subjects must agree to use condoms as an effective barrier method and refrain from sperm donation, and/or their female partners of reproductive potential to use a method of effective birth control, during the treatment with darolutamide and for 1 week after the end of treatment with darolutamide to prevent pregnancy;
• Written informed consent.

You may not qualify if:

• Unresectable prostate cancer;
• Histology of small cell carcinoma prostate cancer or adenocarcinoma with neuroendocrine features;
• Any prior prostate cancer treatment;
• Any active infection requiring IV antibiotics;
• Known additional malignancy that has a life-expectancy \< 2 years;
• Had any of the following within 6 months before randomization: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, heart failure with New York Heart Association Class Functional III or IV;
• Uncontrolled severe hypertension as indicated by a resting systolic BP ≥ 180 mmHg or diastolic BP ≥ 110 mmHg despite medical management;
• A gastrointestinal (GI) disorder or procedure which is expected to interfere significantly with absorption of darolutamide;
• Inability to swallow oral medications;
• Receipt of medications (e.g. finasteride, dutasteride) or agents that are likely to alter serum PSA levels within \<= 42 days or 5 half-lives prior to registration, whichever is shorter.

Sponsors & Collaborators

• Brazilian Clinical Research Institute: lead
• Bayer: collaborator

Study Sites (6)

Santa Casa de Misericórdia de Feira de Santana

Feira de Santana, Estado de Bahia, 44001-032, Brazil

Location

Hospital Ophir Loyola

Belém, Pará, 66063-240, Brazil

Location

Hospital São Marcos

Teresina, Piauí, 64001-280, Brazil

Location

Hospital Universitário Pedro Ernesto

Rio de Janeiro, Rio de Janeiro, 20551-030, Brazil

Location

Hospital de Clínicas Ijuí

Ijuí, Rio Grande do Sul, 98700-000, Brazil

Location

BP - A Beneficência Portuguesa de São Paulo

São Paulo, São Paulo, 01323001, Brazil

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

darolutamide; Leuprolide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Fernando C Maluf, MD

  Brazilian Clinical Research Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2024
• First Posted: October 4, 2024
• Study Start: February 17, 2025
• Primary Completion: March 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: February 11, 2026

Record last verified: 2026-02

Locations

BR (6)