Clinical trial NCT06627530: COACTION Trial - COmbination Androgen bloCkade in inTermediate to hIgh-risk prOstate caNcer
Official title: A Randomized Trial of Neoadjuvant Leuprorelin, Darolutamide or Both Prior to Radical Prostatectomy for Intermediate or High-risk Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Prostate Cancer
Keywords: Prostate Cancer
Radical Prostatectomy
Darolutamide
Neoadjuvant
Lead sponsor: Brazilian Clinical Research Institute
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2024-10-04
Enrollment: 144
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Proportion of patients with minimal residual disease
timeFrame: 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:
measure: Complete biochemical response assessed by serum PSA with the rate of PSA<0,2 ng/dL
timeFrame: 24 weeks
measure: Treatment emergent adverse events and serious adverse events.
timeFrame: 24 weeks
measure: PSA levels at 3 months after prostatectomy.
timeFrame: in 42 weeks
measure: Testosterone levels.
timeFrame: in 42 weeks
measure: Number of positive lymph nodes.
timeFrame: 30 weeks
measure: Number of positive surgical margins.
timeFrame: 30 weeks
measure: Perioperative complications.
timeFrame: 42 weeks
measure: Quality of life using IEEF5 and HRQoL questionnaires pre and post neoadjuvant treatment.
timeFrame: 42 weeks
measure: Downstaging (changes in TNM - Classification of Malignant Tumours stage) based on surgical specimen.
timeFrame: 30 weeks
Other outcomes:
Locations:
city: Feira de Santana
country: Brazil
facility: Santa Casa de Misericórdia de Feira de Santana
state: Bahia
city: Belém
country: Brazil
facility: Hospital Ophir Loyola
state: Pará
city: Teresina
country: Brazil
facility: Hospital São Marcos
state: Piauí
city: Ijuí
country: Brazil
facility: Hospital de Clínicas Ijuí
state: Rio Grande Do Sul
city: Rio de Janeiro
country: Brazil
facility: Hospital Universitário Pedro Ernesto
city: São Paulo
country: Brazil
facility: BP - A Beneficência Portuguesa de São Paulo
Study officials:
affiliation: Brazilian Clinical Research Institute
name: Fernando C Maluf, MD
role: STUDY_CHAIR
References: