Prostate cancer MedDRA version: 20.0 Level: LLT Classification code 10036910 Term: Prostate cancer NOS System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: NUBEQA
Product Name: DAROLUTAMIDE
Pharmaceutical Form: Tablet
INN or Proposed INN: Darolutamide
CAS Number: 1297538-32-9
Current Sponsor code: Darolutamide
Concentration unit: mg milligram
Sponsors
Institut Bergonié
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18, 2. Histological diagnosis of prostate malignancy 3. Cancer without loco-regional or distant metastasis (tumor assessment must comprise at least Pelvic MRI AND thoraco-abdomino-pelvic contrast-enhanced CT-Scan AND Bone Scintigraphy. (Note that additional assessment by PET-Scan is allowed as per investigator judgement), 4. Unfavorable intermediate risk prostate cancer diagnosis defined by the NCCN Guidelines. One of the following criteria is sufficient to define an unfavorable intermediate risk prostate cancer: - Gleason = 7 (4+3) - = 50% of thecore of biopsies need to be positive for adenocarcinoma If these criteria are not being identified, two or three of the following criteria are necessary to define unfavorable intermediate risk prostate cancer: - PSA value between 10-20 ng/ml - Gleason 7 (3+4) or 6 - T2b (clinical or radiological) Note: patients with iT3a (extraprostatic extension) can be included only if gleason score is 6 and PSA less than 20 [22]. 5. Patients newly diagnosed with an unfavorable intermediate risk prostate cancer according to the protocol criteria or previously diagnosed with low risk (Gleason score =65 years) yes F.1.3.1 Number of subjects for this age range 44
Exclusion criteria
Exclusion criteria: 1. Stage T3b-T4 prostate cancer by clinical examination or radiologic evaluation, 2. Patients with Gleason score =8, 3. Patients with PSA > 20 ng/ml, 4. Presence of loco-regional or distant metastasis (MRI/CT-Scan and Bone Scintigraphy), 5. Contra-indications to MRI and to contrast-enhanced CT-scan, 6. Hypogonadism or severe androgen deficiency as defined by screening serum testosterone less than 50 ng/dL or below the normal range for the institution. 7. Previous prostate cancer treated by androgen deprivation, chemotherapy, surgery, or radiotherapy, 8. Patients with previous orchiectomy 9. Patients actively receiving or having received within 6 months prior enrollment any concurrent androgens, anti-androgens, estrogens, or progestational agents, 10. Patients having received ketoconazole, finasteride or dutasteride within 30 days of inclusion, 11. Previous and current malignancies other than prostate cancer within the last 5 years with the exception of adequately treated basal cell or squamous cell carcinoma of the skin, acute lymphoblastic leukemia, non-muscle invasive bladder cancer, 12. Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection), 13. History of cerebrovascular accident (within the last 6 months) 14. Impaired cardiac function including any one of the following: a) Clinically documented myocardial infarction (within the last 6 months) b) History of severe/unstable angina (within the last 6 months) c) History of peripheral artery/coronary bypass surgery (within the last 6 months) d) History of or presence of congestive heart failure according to the New York Heart Association (NYHA) class 3 or 4 with LVEF < 45% or below the institutional lower limit of the normal range (whichever is higher) as determined by locally read echocardiogram or multi-gated acquisition scan performed in the last 6 months e) History of or prensece of risk factors for QT interval prolongation f) History of or presence of clinically significant ventricular or atrial tachy-arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes) g) Clinically significant resting bradycardia (< 50 beats per minute) h) History of Mobitz II second degree or third degree heart block without use of ventricular-paced pacemaker i) History of or presence of clinically significant hypotension (e.g. systolic blood pressure < 86 mmHg on 2 consecutive measurements) j) ECG demonstrating equal to or greater than grade III toxicity according the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 15. Uncontrolled hypertension 16. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery), 17. Major surgery within 4 weeks prior enrolment except pelvic lymph-nodes dissection (extended or limited), 18. Known hypersensitivity to any involved study drug or of its formulation components, to natural gonadotrophin releasing hormone (GnRH) or its analogues 19. Galactose intolerance, total lactase deficiency or glucose-galactose malabsorption syndrome 20. Men who are not using an effective method of contraception as previously described 21. Use of herbal or alternative remedies that may affect hormonal status such as Prostasol or PC-SPES, 22. History of non-compliance to medical regimens or i
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the preliminary signs of antitumor activitity of darolutamide when prescribed for 6 months in association with radiotherapy in patients with unfavorable intermediate risk prostate cancer. Activity will be measured in terms of biological response defined as PSA =0.1ng/ml and measured 6 months after randomization. ;Secondary Objective: Independently for each treatment strategy: assessment of antitumor activity in terms of : oBiological response (PSA =0.1ng/ml) measured oat the end of darolutamide or ADT, o2 months following randomization, o3, 6, and 9 months post-radiotherapy, o2, 3 and 5 years following randomization oBiolochemical Progression-free survival, oMetastases-free survival, oDisease-free survival, oProstate cancer-specific survival, oOverall-survival, oTime to testosterone recovery •Independently for each treatment strategy: Assessment of the safety profile of the therapeutic strategy and assessment of the quality of life before, during and after treatment;Primary end point(s): Efficacy will be assessed in terms of biological response defined as a PSA concentration =0.1ng/ml at 6 months post-randomization;Timepoint(s) of evaluation of this end point: Biochemical response at 6 months post-randomization will be reported. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Biochemical disease progression is defined asa PSA level higher than PSA nadir + 2 ng/mL according to Phoenix’s criteria. 2. Biochemical progression-free survival is defined as the delay between the date of randomization and the date of biochemical disease progression or death, whichever comes first. Median bPFS, as well as 2-, 3-, and 5-year bPFS will be reported. 3. Metastasis Free Survival is defined as the delay between the date of randomization and the date of metastasis diagnosis (imaging and/or biopsy). Median MFS, as well as 2-, 3- and 5-year MFS will be reported. 4. Disease Free Survival (DFS) is defined as the delay between randomization and the first of the following events: o biological PSA progression defined as level higher than PSA nadir + 2 ng/mL according to Phoenix’s criteria o progression (local, regional, distant) o death (any cause). Median DFS, as well as 2-, 3- and 5-year DFS will be reported. 5. Prostate cancer-specific Survival (PCSS) is defined as the delay between the date of randomization and the date of prostate cancer-related death. Median PCSS, as well as 2-, 3- and 5-year PCSS will be reported. 6. Overall survival is defined as the delay between the date of randomization and the date of death (all cause). Median OS, as well as 2-, 3- and 5-year OS will be reported. 7. Time to testosterone recovery defined as the time from randomization to the time when serum of total testosterone level increases to above the lower limit of the normal range. 8. The safety profile (acute, i.e. < 3 months and late 2-, 3- and 5-year) of each treatment strategy will be graded using NCI CTCAE v5. Both AE and SAE will be coded according to the standardized medical terminology MedDRA. 9. Quality of life will be assessed as follows (M0, M3, M6, M12, M24, M60): oAs per the EORTC QLQ-C30 questionnaire and prostate cancer module PR-25 oAssessment of erectile dysfunction, as per IIEF5 oAssessement of symptoms of benign prostatic hyp | — |
Countries
France
Contacts
Public ContactRegulatory Affairs Management Desk
Institut Bergonié
Outcome results
None listed