Apalutamide for Metastatic prostate cancer

Inclusion criteria

• {"criterion_text":"- ≥ 18 years of age, < 80 years of age\n- 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\n- Histologically confirmed adenocarcinoma of the prostate\n- High-risk disease defined by a total Gleason Sum Score ≥ 4+4 (=Grade Groups [GG] 4-5), PSA >20 ng/ml, or ≥cT2c based on digital rectal examination or ≥cT3 or cN+ based on preoperative imaging\n- Conventional imaging negative for metastases\n- 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\n- Candidate to RP with PLND\n- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1\n- Adequate organ function\n- Able to receive ADT for at least 18 months, based on cardiovascular risk assessment and the investigator’s assessment\n- Be able to swallow whole study drug tablets"}

Exclusion criteria

• {"criterion_text":"- Distant metastasis based on conventional imaging (CT scan or bone scintigraphy). Nodal disease below the iliac bifurcation (clinical stage N1 at CT scan) is not an exclusion criterion.\n- Prior hormonal treatment (GnRHa, agonist or antagonist)\n- Prior bilateral orchiectomy\n- History of prior systemic or local therapy for prostate cancer, including pelvic radiation and whole gland or focal ablative modalities for prostate cancer\n- Use of any investigational agent ≤4 weeks prior to RP or any therapeutic procedure for prostate cancer at any time\n- Major surgery ≤4 weeks prior to RP\n- Any of the following within 12 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\n- Human immunodeficiency virus-positive subjects with 1 or more of the following: (1) not receiving highly active antiretroviral therapy; (2) had a change in antiretroviral therapy within 6 months of the start of screening; (3) receiving antiretroviral therapy that may interfere with study drug (consult Sponsor for review of medication prior to enrolment); (4) CD4 count <350 at screening; (5) AIDS-defining opportunistic infection within 6 months of start of screening; (6) active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction\n- History of seizure; any condition that may predispose to seizure\n- Patients taking any prohibited medications (as reported in the protocol) should not be included\n- Gastrointestinal conditions affecting absorption\n- Known or suspected contraindications or hypersensitivity to apalutamide, GnRHa or any of the components of the formulations\n- Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject\n- Active malignancies other than prostate cancer. The only allowed exceptions are: non-muscle invasive bladder cancer (NMIBC); skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured; breast cancer (adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence); malignancy that is considered cured with minimal risk of recurrence."}

Primary endpoints

• {"endpoint_text":"- Radiological progression-free survival (RPFS), evaluated based on PSMA PET/CT","definition_or_measurement_approach":"Evaluated based on PSMA PET/CT"}

Secondary endpoints

• {"endpoint_text":"- Adverse events (AEs)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Biochemical progression-free survival (BPFS)* Progression-free survival 2 (PFS2) Time to castration-resistant PCa (CRPC) Percentage of subjects receiving postoperative radiotherapy Overall survival (OS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change from baseline over time in Expanded Prostate Cancer Index (EPIC-26) and EQ-5D-5L","definition_or_measurement_approach":"Change from baseline over time using EPIC-26 and EQ-5D-5L instruments"}

Italy

Earliest CTIS Part Ii Submission Date

18-07-2024

Latest Decision Or Authorization Date

07-04-2026

Processing Time Days

628

Number Of Sites

11

Number Of Participants

94

Primary sponsor

Full Name

Universita' Degli Studi Di Torino

Organisation Type

Educational Institution

Country Of Registered Address

Italy