High risk adenocarcinoma of the prostate after radical prostatectomy (RPE) MedDRA version: 20.0 Level: PT Classification code 10060862 Term: Prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Westfälische Wilhelms-Universität Münster c/o Universitätsklinikum Münster, Geschäftsbereich Recht u. Drittmittel
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Signed informed consent form (ICF) 2. Men = 18 years of age 3. Patients with histologically confirmed adenocarcinoma of the prostate after radical prostatectomy 4. Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 5. Exclusion of metastatic disease by CT-scan of abdomen (MRI of abdomen is possible) and bone scan prior to study inclusion. A PSMA PET-CT/MRI is possible. In this case it has to be done with a diagnostic CT/MRI with contrast media and not with a low dose CT-scan only. In case PSMA-PET imaging has been done, a bone scan can be omitted. CT/MRI, and bone-scan imaging or PSMA PET-CT/MRI administered =12 weeks before RPE may be used for screening 6. Patients after RPE must meet the d’Amico criteria for high risk of disease recurrence (T-stage and Gleason-score determined after radical prostatectomy) i.e. 1 of the following after RPE: 1) Gleason score =8, any T-stage, any iPSA or 2) Gleason score 6 or 7, any iPSA and =pT3 or 3) iPSA >20 ng/ml, any Gleason score, any T-stage. 7. Patients have to have recovered from radical prostatectomy within eight weeks to be able to take part in the study 8. PSA must have declined below 0.2 ng/ml prior to randomization 9. Adequate hematologic, hepatic, and renal function: • Hematologic i) Haemoglobin = 9.0 g/dL independent of transfusions ii) Neutrophils = 1.5 Ths./µL • Hepatic i) Total Bilirubin ==65 years) yes F.1.3.1 Number of subjects for this age range 95
Exclusion criteria
Exclusion criteria: 1. Any chronic medical condition requiring a higher dose of corticosteroid than 10mg prednisone/prednisolone q.d. 2. Prior cytotoxic chemotherapy or biologic therapy for the treatment of prostate cancer 3. Prior or current treatment of prostate cancer with apalutamide, enzalutamide, darolutamide, or other investigational agents targeting the androgen receptor 4. Prior therapy with Sipuleucel-T or other vaccination or immunogenic therapy for the treatment of prostate cancer 5. Prior treatment with abiraterone acetate or other androgen synthesis inhibitors (e. g. ketoconazole, TAK700, TOK001) 6. Use of 5-a reductase inhibitors (eg, dutasteride, finasteride) =4 weeks prior to randomization 7. Prior surgical castration or medical castration using LHRH-Agonists or GnRH-Antagonists 8. Prior or current radiation or radionuclide (including radium-223 dichloride) therapy for treatment of prostate cancer (adjuvant radiation of the prostate bed without involvement of the regional lymph node template as by standard of care in case of positive surgical margins (R1) is allowed) 9. Prior or current systemic treatment with an azole drug (e.g. fluconazole, itraconazole) within 4 weeks of Cycle 1, Day 1 10. Any lymph node or distant metastasis 11. History of seizures or condition that may predispose to seizure (including, but not limited to prior stroke, transient ischemic attack or loss of consciousness =1 year prior to randomization; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect). 12. Current or prior treatment with anti-epileptic medications for the treatment of seizures 13. Management of cardiovascular risk factors, such as hypertension, diabetes or dyslipidaemia should be optimised as per standard of care before treatment with apalutamide will be initiated 13.1. Uncontrolled hypertension (systolic BP =140 mmHg or diastolic BP =90 mmHg. For patients with relevant comorbidities (e.g. diabetes) systolic BP =130 mmHg or diastolic BP =80 mmHg). Patients with a history of hypertension are allowed provided that blood pressure is controlled by anti-hypertensive treatment 13.2. Patients with uncontrolled diabetes defined as HbA1c =7.5% 13.3. Patients with a dyslipidemia defined as LDL cholesterol >100 mg/dl. For patients with a dyslipidemia defined as LDL cholesterol >100 mg/dl and SCORE-value of 1-5%: In case of a SCORE-value of <1% a LDL cholesterol level of up to 115 mg/dl is acceptable. In case of increased LDL cholesterol above these values a statin-therapy can be initiated and a rescreening within 4 weeks is possible 13.4. Cardiovascular risk assessment via an appropriate score (e.g. the SCORE-Chart for the European high/low risk score from the European Society of Cardiology) and = borderline risk i.e. 10% of developing cardiovascular events within 10 years without prior cardiovascular disease 14. Active or symptomatic viral hepatitis or chronic liver disease or HIV 15. History of pituitary or adrenal dysfunction 16. Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 12 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of <50% at baseline, or clinically relevant pelvic lymphocele after radical prostatectomy as evaluated by clinical examination and/or pelvic ultrasound (if a risk is present, patients may be al
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine if adjuvant apalutamide in prostate cancer patients at high risk of developing subsequent metastatic disease results in prolonged biochemically recurrence-free survival after radical prostatectomy (RPE) in comparison to standard of care (SOC). ;Secondary Objective: 1. To characterize the safety and tolerability of apalutamide in subjects with high-risk, localized or locally advanced prostate cancer having received RPE 2. To determine if apalutamide in subjects with high-risk, localized or locally advanced prostate cancer having received RPE results in an improvement of PSADT, i.e. increased PSADT in case of BCR ;Primary end point(s): Progression-free survival (PFS). This endpoint is defined as time interval from randomization until BCR, metastases, or death from any cause, whichever occurs first. BCR is defined as a PSA = 0.2 ng/ml that has risen on at least two separate occasions at least four weeks ± 3 days apart and measured by the central PSA-lab. The time of BCR is then backdated to the time of the first increased PSA measurement. Metastatic disease will be defined as the presence of bone metastases visualized on bone scan prostate cancer working group 3 (PCWG3)-criteria; and/or visceral (e.g. liver, lung, brain) or extra-pelvic nodal metastases visualized on CT scan (or MRI scan) (RECIST 1.1-criteria). If deemed indicated by the study physician a PSMA-PET-CT/MRI can be done instead. Evaluations will be performed every 6 months once BCR occurred or sooner if clinically indicated. For a patient with none of these events before the end of follow-up, observation of PFS will be censored at the date of his last follow-up examination.;Timepoint(s) of evaluation of this end point: At every study visit. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Safety and tolerability assessed on the basis of adverse events, more precisely adverse events, serious adverse events, adverse reactions, and serious adverse reactions 2) PSA doubling time (PSADT). In case of an BCR, PSA kinetics as the PSADT are calculated based on the monthly PSA measurements during the first six months after the BCR. The values used to determine the BCR are included in the calculation of PSA kinetics as well. In case of a sudden incline of PSA to values close to 0.5 ng/ml, a follow-up (radiation) therapy or next generation imaging diagnostics in search for potential metastasis that may lead to subsequent therapy might be started before the 6 months since BCR have passed. In this case, PSA kinetics will be calculated based on all PSA measurements available since BCR but at least based on 3 PSA measurements with at least 4 weeks in-between each measurement. PSADT is calculated according to Pound et al. by the natural log of 2 (0.693) divided by the slope of the relationship between the log of PSA and time of PSA measurement (i.e. time from BCR) for each patient. PSADT can also be assessed using the MSKCC PSADT calculator (https://www.mskcc.org/nomograms/prostate/psa_doubling_time) using the above definitions. ;Timepoint(s) of evaluation of this end point: 1) Ongoing basis from signed informed consent form until BCR occurred and PSADT was calculated or when distant metatstasis occurred (both with or without BCR) 2) If BCR occurs up to 6 months later | — |
Countries
Austria, Germany
Contacts
Public ContactUniv.-Prof. Dr. med Martin Bögemann
Klinik für Urologie und Kinderurologie am UKM Münster
Outcome results
None listed