Clinical trial NCT05778097: Adjutant Apalutamide Plus ADT in Post-RP Patients With High Risk of Recurrence (ARES Study)
Official title: Adjuvant Androgen Deprivation Therapy Combined With Apalutamide for Prostate Cancer Patients Post Radical-prostatectomy With High-risk of Reoccurrence: a Prospective, Single-arm, Multicenter Trial (ARES Study)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Prostate Cancer
Biochemical Recurrence
High Risk
Keywords: prostate cancer biochemical recurrence
apalutamide
adjuvant treatment
post-radical prostatectomy
Lead sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Sponsor class: OTHER
Collaborators: name: Xian-Janssen Pharmaceutical Ltd.
First posted: 2023-03-21
Enrollment: 103
Sex: MALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: ARES is a multicenter, single-arm, phase 2 trial to evaluate the efficacy and safety of ADT in combination with apalutamide as an adjuvant regimen for patients with high risk of recurrence after radical prostatectomy.


Eligibility criteria: Key Inclusion Criteria:

1. Prostate cancer diagnosed histologically or cytologically in males ≥18 years and ≤75 years of age;
2. Localized prostate cancer (assessed by conventional imaging tools such as CT and bone scan) within 12 weeks after radical prostatectomy;
3. PSA \< 0.1 ng/ml within 8 weeks after surgery;
4. Postoperative CAPRA-S score ≥ 6, suggesting a higher risk of recurrence;
5. ECOG score at 0-1 according to the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale;
6. Adequate organ functions:

   Hematology (within 14 days before treatment: no blood transfusion, no use of granulocyte colony-stimulating factor, no use of other drugs for correction)：
   1. Neutrophil count (NE) ≥1.5×109/L;
   2. Hemoglobin (HGB) ≥ 90 g/L;
   3. Platelet count (PLT) ≥100×109/L; Coagulation function (no blood product transfusion within 14 days before treatment): international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5× upper limit of normal (ULN); Blood biochemistry (liver and kidney function)：

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   1. Creatinine clearance ≥ 30 mL/min;
   2. Total bilirubin (TBIL) ≤ 1.5× ULN;
   3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5× ULN;
7. Ability to provide written informed consent form (ICF) and ability to understand and agree to adhere to study requirements and schedule of assessments;
8. Patients of childbearing potential must be willing to use highly effective contraception during the study and for 12 weeks after the last dose of treatment.

Key Exclusion Criteria:

1. Patients with neuroendocrine, small cell, or sarcomatoid features in prostate histopathology;
2. Pelvic lymph node metastasis (cN1) or distant metastasis (cM1) indicated preoperatively by traditional imaging procedures such as CT or bone scan;
3. Prior treatment by androgen deprivation therapy (including medication or surgical castration), focal therapy for prostate cancer, or radiotherapy and chemotherapy for prostate cancer;
4. Prior treatment with second-generation antiandrogen (e.g., abiraterone, apalutamide, enzalutamide, darolutamide, etc.);
5. Any major surgery (other than radical resection) requiring general anesthesia within 28 days prior to the first dose of the study;
6. Other malignancies present or occurred in the past 2 years, except cured non-melanoma skin cancers and superficial bladder tumors (Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor infiltrating of basement membrane);
7. Arterial/venous thrombotic events (such as cerebrovascular accident, deep vein thrombosis and pulmonary embolism) or anticoagulant therapy with warfarin or heparin within 6 months before the study;
8. Corrected QT interval (QTc) of heart rate \> 500 ms; patients with QTc prolonged but \< 500 ms should be assessed by a cardiologist for eligibility;
9. Severe cardiovascular diseases: myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmia; Classes III-IV cardiac insufficiency according to the New York Heart Association (NYHA) Classification, or left ventricular ejection fraction (LVEF) \< 50% indicated in cardiac Doppler ultrasound;
10. Allergy to any study drug or excipients;
11. Active viral hepatitis requiring treatment as determined by the Investigators:

    1. Chronic hepatitis B, with hepatitis B virus (HBV) deoxyribonucleic acid (DNA) ≥ 500 IU/mL (2500 copies/mL) (HBV DNA testing only for patients with positive test for Hepatitis B surface antigen or core antibody);
    2. Positive for Hepatitis C virus (HCV) ribonucleic acid (RNA) test (HCV RNA test only for patients with positive HCV antibodies);
12. Any present active autoimmune disease or history of autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism), or known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation, or long-term heavy use of hormones or other immunomodulators, or other conditions assessed by the Investigator as having an impact on study treatment;
13. Active infection;
14. History of interstitial lung disease or uncontrolled systemic disease, including diabetes, hypertension, acute lung disease, etc.;
15. Known to have human immunodeficiency virus (HIV) infection;
16. History of epilepsy or conditions that may induce epilepsy
17. The presence of an underlying medical condition alcohol/drug abuse or dependence that is detrimental to the administration of the study drugs, or that may affect the interpretation of the results, or that places the patient at high risk of developing treatment complications;
18. Men who have sexual activity with women of childbearing potential, unless they:

    Agree to use condom or spermicidal foam/gel/diaphragm/cream/suppository Agree not to donate sperm during the study and for at least 3 months after receiving the last dose of study drug No birth plan during the study or within 3 months after the last dose of study drug
19. Concurrent participation in another therapeutic clinical study.

Primary outcomes:
measure: Two-year biochemical progression-free survival
timeFrame: 24 months
Secondary outcomes:
measure: Event-free survival rate
timeFrame: from initiation with apalutamide up to 36 months
measure: Biochemical progression-free survival
timeFrame: 60 months
measure: Metastasis-free survival (MFS)
timeFrame: 60 months
measure: Quality of life (QoL) assessed by FACT-P scale
timeFrame: 24 months
measure: Two-year testosterone recovery rate
timeFrame: 24 months
measure: Time to testosterone recovery
timeFrame: From initiation of apalutamide plus ADT up to 36 months
measure: Number of Adverse Events Number of Adverse Events Number of Adverse Events Adverse events (AEs)
timeFrame: From initiation of apalutamide plus ADT to 30 days after last dose of apalutamide
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Nanjing First Hospital, Nanjing Medical University
state: Jiangsu
city: Nanjing
country: China
facility: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
state: Jiangsu
city: Nantong
country: China
facility: Nanjing Tumor Hospital
state: Jiangsu
Study officials:
References: