Surgical Treatment With or Without Apalutamide in Subjects With High Risk Prostate Cancer Who Are Candidates for Radical Prostatectomy and Staged as Oligometastatic With PSMA-PET
This is a phase 2, open-label, randomized study of adjuvant treatment in subjects with high-risk prostate cancer who are candidates for RP with PLND based on M0 status at conventional imaging, but staged as oligometastatic with PSMA PET/CT (performed as routine practice, according to recent evidence on high-risk prostate cancer patients). Ninety-four subjects will receive apalutamide plus ADT or ADT alone after surgery. ADT is defined as medical castration (ie, gonadotropin-releasing hormone analogues \[GnRHa, agonist or antagonist\]). Subjects will be randomly assigned in a 1:1 ratio to receive apalutamide plus ADT or ADT alone. Patients randomized to receive ADT + apalutamide or ADT alone will begin their adjuvant treatment 4 weeks (28 to 32 days) after surgery. A first dosage of PSA and testosterone will be performed just before starting adjuvant therapy but not before 28 days from surgery. Subsequently, PSA and testosterone dosage and clinical visits will be performed after 3 months from surgery and every 3 months until completion of study. PSMA PET/CT scan will be performed yearly, or in case of PSA progression. The Posttreatment Follow-up Phase will begin after 18 months of ADT and will last for 6 months, until study completion. Afterwards, patients will continue their follow-up according to the best clinical practice.
• ≥ 18 years of age, \< 80 years of age
• Signed informed consent form (ICF) indicating that the subject understands the purpose and procedures required for the study and is willing to participate in the study; subjects must be willing and able to adhere to the prohibitions and restrictions specified in this protocol (Section 4.3)
• Histologically confirmed adenocarcinoma of the prostate
• High-risk disease defined by a total Gleason Sum Score ≥ 4+4 (=Grade Groups \[GG\] 4-5)
• Conventional imaging negative for metastases
• Presence of low volume metastatic disease at pre-surgery PSMA PET/CT. The metastatic burden is classified according to the definition used in the CHARTEED trial applied to PSMA PET/CT, where high metastatic burden was defined as four or more bone metastases with one or more outside the vertebral bodies or pelvis, or visceral metastases, or both; all other assessable patients were considered to have low metastatic burden
• Candidate to RP with PLND
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
• Adequate organ function determined by the following laboratory values:
∙ Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin within normal limits, ie, ≤ 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 \<1.8 mg/dL;
‣ Platelets ≥75.000/dL, without transfusion and/or growth factors within 56 days prior to RP;
‣ Haemoglobin ≥11.0 g/dL, without transfusion and/or growth factors within 56 days prior to RP;
⁃ Able to receive ADT for at least 18 months, based on cardiovascular risk assessment and the investigator's assessment
⁃ Be able to swallow whole study drug tablets