Apalutamide for High-risk localized or locally advanced prostate cancer

Inclusion criteria

• {"criterion_text":"- Subject must be a man in the age of 18 – 79 years.\n- Each subject must sign an informed consent form (ICF) indicating that he 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- Indicated and planned to receive primary RT for prostate cancer.\n- Histologically confirmed adenocarcinoma of an intact prostate and one of the following risk factors for EUA high-risk localized or locally prostate cancer at diagnosis: • Localized high-risk prostate cancer: PSA >20 ng/mL or GS >7 (ISUP grade 4/5) or cT2c, • Locally advanced high-risk prostate cancer: cT3 – 4 or cN+, any PSA, any ISUP grade; Note: Documentation of clinical T stage (cT2c, cT3, cT4) may be obtained from any clinical assessment acceptable for clinical T staging including digital rectal examination (DRE) and MR. Documentation of N and M stage may be obtained from conventional imaging (technetium bone scan, and prostate MR or abdominopelvic CT) or molecular imaging (68Ga PSMA PET/CT).\n- Modified Charlson comorbidity index (CCI) ≤4.\n- Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade 0 or 1.\n- Adequate organ function determined by the following local laboratory values: • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5x upper limit of normal (ULN); total bilirubin ≤1.5x ULN, • Serum creatinine ≤2x ULN, •\tThrombocytes ≥140x10^9/L, •\tHemoglobin ≥120 g/L (no transfusion is allowed within 3 months prior to enrollment).\n- To avoid risk of drug exposure through the ejaculate (even men with vasectomies), subjects must use a condom during sexual activity while on study drug and for 3 months following the last dose of study drug. Donation of sperm is not allowed during the Treatment Phase and for 3 months following the last dose of study drug.\n- Be able to swallow whole study drug tablets, undergo prostate MR, prostate seeds implantation and prostate radiotherapy in supine position."}

Exclusion criteria

• {"criterion_text":"- Presence of distant metastasis on conventional imaging or 68Ga PSMA/PET (clinical stage M1). Isolated pelvic nodal disease below the iliac vessels bifurcation (clinical stage N1) is not an exclusion.\n- Prior treatment with systemic glucocorticoids ≤4 weeks prior to enrollment or subject expected to require long-term use of corticosteroids during the study.\n- Use of first-generation antiandrogen (e.g., bicalutamide) ≤4 weeks prior to enrollment.\n- Use of 5-α reductase inhibitors (e.g., dutasteride, finasteride) ≤4 weeks prior to enrollment.\n- History of seizure or any condition that may predispose to seizure (including, but not limited to prior stroke, transient ischemic attack or loss of consciousness ≤1 year prior to enrollment; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect).\n- Current or prior treatment with anti-epileptic medications for the treatment of seizures.\n- Gastrointestinal conditions affecting absorption.\n- Known or suspected contraindications or hypersensitivity to apalutamide or LHRH agonists/antagonist 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- Use of any investigational agent ≤4 weeks prior to enrollment.\n- Current chronic use of opioid analgesics, for ≥3 weeks for oral or ≥7 days for non-oral formulations.\n- Major surgery ≤4 weeks prior to enrollment.\n- Prior treatment with LHRH agonist/antagonist analogue or anti-androgen or both for >3 months prior to enrollment.\n- Bilateral orchiectomy.\n- History of pelvic radiation.\n- Prior systemic (e.g., chemotherapy) or local (e.g., radical prostatectomy, cryotherapy) treatment for prostate cancer.\n- Prior treatment with enzalutamide, abiraterone acetate, orteronel, galeterone, ketoconazole, aminoglutethimide, estrogens, megestrol acetate, and progestational agents (including cyproterone acetate) for prostate cancer."}

Primary endpoints

• {"endpoint_text":"- 5-year biochemical control rate defined as a percentage of surviving patients without biochemical progression after 5 years since the treatment start (assessed by Kaplan-Meier estimate).","definition_or_measurement_approach":"Assessed by Kaplan-Meier estimate. Biochemical progression is defined according to RTOG – ASTRO Phoenix consensus criteria (a rise by 2 ng/mL or more above the nadir PSA with the date of failure determined \"at call\")."}

Secondary endpoints

• {"endpoint_text":"- Major secondary endpoint: Metastasis free survival based on PSMA PET/CT (assessed by Kaplan-Meier estimate).\n- 5-year biochemical control rate with PSA <0.2 ng/mL.\n- 5-year prostate cancer specific survival.\n- 5-year overall survival (OS). OS is defined as the time from enrollment to date of death from any cause.\n- Incidence of acute and late side effects and complications associated with radiotherapy and systemic treatment evaluated by Common Terminology Criteria of Adverse Event (CTCAE) and Patient Reported Outcomes (PRO) including QoL questionnaires.\n- Effect of the planned interventions on QoL (I-PSS, EPIC-26, FACT-P, EQ-5D-5L, PRO-CTCAE™ (short version)).","definition_or_measurement_approach":"Metastasis free survival assessed by Kaplan-Meier estimate based on PSMA PET/CT. 5-year biochemical control rate with PSA <0.2 ng/mL assessed at 5 years. Prostate cancer specific survival and overall survival measured from enrollment (OS = time from enrollment to death from any cause). Adverse events evaluated by CTCAE and PRO (QoL questionnaires). QoL instruments listed: I-PSS, EPIC-26, FACT-P, EQ-5D-5L, PRO-CTCAE™ (short version)."}

Slovakia

Earliest CTIS Part Ii Submission Date

12-09-2024

Latest Decision Or Authorization Date

25-10-2024

Processing Time Days

43

Number Of Sites

1

Number Of Participants

48

Primary sponsor

Full Name

Vychodoslovensky Onkologicky Ustav a.s.

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Slovakia

Third parties

• {"country":"Czechia","full_name":"Twma s.r.o.","duties_or_roles":"Codes: 1, 12, 15; Local pharmacovigilance","organisation_type":"Pharmaceutical company"}