patients with locally advanced T4 high risk prostate cancer
Conditions
Interventions
Trade Name: Erleada 60 mg Filmtabletten
Product Name: Erleada 60 mg Filmtabletten
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Apalutamide
CAS Number: 956104-40-8
Concentration unit: m
Sponsors
Universität des Saarlandes
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1.Male of 18 to 80 years of age, inclusive. 2.Histologically confirmed adenocarcinoma of the prostate without complete neuroendocrine differentiation or small cell features 3.cT4 PCa, considered as primary inoperable because of a fixed mass defined by digital rectal examination, confirmed by advanced disease in MRI 4.Eastern Cooperative Oncology Group Performance Status 0 or 1, patients must and are expected to be fit and willing to undergo radical prostatectomy within 6 to 9 months after start of study treatment 5.Adequate organ function determined by the following laboratory values: a.Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin less than twice the upper limit of normal b.Platelets =100,000/?L, independent of transfusion and/or growth factors within 1 month prior to enrolment 6.At least 4 weeks must have elapsed from the use of 5-alpha reductase inhibitors and estrogens prior to enrolment 7.No irradiation of the pelvis 8.Be able to swallow whole study drug tablets 9.Not candidate for radiotherapy or who deny radiotherapy 10.Must agree to wear a condom when engaging in any activity that allows for passage of ejaculate to another person while on study drug and for 3 months following the last dose of study drug 11.Must agree not to donate sperm for the purpose of reproduction during the study and for a minimum 90 days after receiving the last dose of IMP 12.Must sign an ICF indicating that he understands the purpose of and procedures required for the study and is willing to participate in the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1.Presence of distant metastasis (clinical stage M1) after MRI, CT abdomen and bone scan Note: Patients with distant metastases only detectable in PSMA-PET/CTs are allowed to be included in the trial when conventional imaging (CT and bone scan) is negative for distant metastases 2.Pathological finding consistent with small cell, ductal, or complete neuroendocrine prostate cancer 3.Prior treatment with second generation anti-androgens 4.Prior treatment with CYP17 inhibitors 5.Prior treatment with systemic glucocorticoids =4 weeks prior to enrolment or patient expected to require long-term use of corticosteroids during the study 6.Use of 5-a reductase inhibitors (eg, dutasteride, finasteride) =4 weeks prior to enrolment 7.Major surgery =4 weeks prior to enrolment 8.Prior treatment with radiopharmaceutical agents 9.Prior chemotherapy for prostate cancer 10.History of any pelvic radiation 11.Bilateral orchiectomy 12.History or evidence of any of the following conditions: any prior malignancy (other than adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission) within 5 years prior to enrolment; severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events, or clinically significant ventricular arrhythmias within 6 months; uncontrolled hypertension; history of seizure or convulsion; gastrointestinal disorder affecting absorption; active infection; and, any other condition that, in the opinion of the investigator, would impair the patient's ability to comply with study procedures 13.Presence of any of the following cardiologic criteria: a) Mean resting QTc >470 msec b) In patients with a history of risk factors for QT prolongation and in patients receiving concomitant medicinal products that might prolong the QT interval, the benefit-risk ratio including the potential for Torsade de pointes will be carefully assessed and patients will be excluded if the benefit-risk ratio is considered as unfavorable. 14.Active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction 15.Any active infection requiring systemic therapy 16.Known or suspected contraindications or hypersensitivity to apalutamide, or GnRH agonists or any of the components of the formulations 17.Patient is eligible for PROTEUS study (all patients with operable, non T4 disease) 18.Patient has received another investigational medication (including investigational vaccines) or used another invasive investigational medical device within 30 days before the planned first dose of the IMP of this study or is currently enrolled in another investigational study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess operability in patients with locally advanced T4 high risk prostate cancer upon inductive pre-prostatectomy treatment with apalutamide plus ADT for a duration of up to 6 months.;Secondary Objective: Secondary objectives are • to assess the feasibility of treatment • to assess the effect of the treatment on patients’ quality of life • to characterize PSA levels post-surgery without any further therapy and biochemical complete remission 6 months after surgery • to describe the time to biochemical recurrence (BCR) • to assess complete pathological response and negative margin status • to assess safety and tolerability of treatment. ;Primary end point(s): The primary endpoint of this study is the proportion of patients with operability - as assessed by MRI (experienced radiologist), transrectal ultrasound, and clinical examination (two experienced uro oncological surgeons) - upon inductive pre-prostatectomy treatment for a duration of up to 6 months. For patients who have not reached the PSA nadir after the 6-month period and are not considered as operable, the inductive therapy with apalutamide plus ADT can be expanded for a maximum of additional 3 months until the nadir is reached.;Timepoint(s) of evaluation of this end point: Upon inductive pre-prostatectomy treatment of 6 months. For patients who have not reached the PSA nadir after the 6-month period and are not considered as operable, the inductive therapy with apalutamide plus ADT can be expanded for a maximum of additional 3 months until the nadir is reached. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints of this study are: • Proportion of patients with pT0 (pCR) in prostatectomy specimens (complete pathological response) • Proportion of patients with negative margin specimen from prostatectomy according to the histology results after surgery • Proportion of patients with 0.2 ng/mL and rising obtained at two consecutive scheduled study visits after prostatectomy. • Time to biochemical recurrence (BCR) after prostatectomy, if possible. • The change in ECOG performance status as well as the change in some hematologic parameters (hemoglobin, leukocytes, lymphocytes, neutrophils, platelets), and the change in levels of serum testosterone/hormones from baseline at different study visits. • Time to treatment discontinuation. • Safety and tolerability with regard to adverse events (AEs), abnormal laboratory results, and perioperative complications.;Timepoint(s) of evaluation of this end point: Different timepoints depending on the end point. For details please refer to section E.5.2 | — |
Countries
Germany
Contacts
Public ContactKlinik für Urologie
Universität des Saarlandes
Outcome results
None listed