A MULTINATIONAL, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED,PHASE III EFFICACY AND SAFETY STUDY OF ODM-201 IN MEN WITH HIGH-RISK NON-METASTATIC CASTRATION-RESISTANT PROSTATE CANCER
- Conditions
- High-risk, non-metastatic castration-resistant prostate cancer (MedDRA: hormonerefractory prostate cancer)MedDRA version: 17.0Level: LLTClassification code 10066489Term: Progression of prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 17.0Level: PTClassification code 10062904Term: Hormone-refractory prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-003820-36-IT
- Lead Sponsor
- Orion Corporation Orion Pharma
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Male
- Target Recruitment
- 1500
1. Written informed consent (IC) obtained.
2. Males aged > = 18 years.
3. Histologically or cytologically confirmed adenocarcinoma of prostate without neuroendocrine differentiation or small cell features.
4. Progressive CRPC is defined as 3 consecutive rising PSA level during ADT at least 1 week apart, resulting in 2 > 50% increases over nadir, with the last value >=2 ng/ml despite castrate level of serum testosterone. If the patient has a history of antiandrogen use, the
most recent PSA value must be obtained at least 4 weeks after antiandrogen withdrawal.
5. Castrate level of serum testosterone (< 1.7 nmol/l [50 ng/dl]) on GnRH agonist or antagonist therapy or after bilateral orchiectomy. Patients who have not undergone bilateral orchiectomy must continue GnRH therapy during the study.
6. PSADT of >= 10 months and PSA > 2 ng/ml at screening.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
8. Blood counts at screening: haemoglobin = 9.0 g/dl, absolute neutrophil count = 1500/µl (1.5x10^9/l), platelet count = 100,000/µl (100x10^9/l ) (patient must not have received any growth factor or blood transfusion within 7 days of the haematology laboratory obtained at screening).
9. Screening values of serum alanine aminotransferase (ALT) and/or aspartate transaminase (AST) <=2.5 x upper limit of normal (ULN), total bilirubin >01.5 x ULN (except patients with a diagnosis of Gilbert’s disease), creatinine <=2.0 x ULN.
10. Sexually active patients, unless surgically sterile, must agree to use condoms as an effective barrier method during the study treatment and for 3 months after the end of the study treatment.
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 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1200
1. History of metastatic disease or presence of detectable metastases by blinded central reading. Presence of pelvic lymph nodes < 2 cm in short axis below the aortic bifurcation is allowed.
2. Symptomatic local-regional disease that requires medical intervention including moderate/severe urinary obstruction or hydronephrosis due to prostate cancer.
3. Acute toxicities of prior treatments and procedures not resolved to grade <=1 or baseline before randomisation.
4. Prior treatment with: second generation AR inhibitors such as enzalutamide, ARN-509, ODM-201, other investigational AR inhibitors,
CYP17 enzyme inhibitor such as abiraterone acetate, TAK-700 or
oral ketoconazole longer than for 28 days.
5. Use of estrogens, 5-a reductase inhibitors (finasteride, dutasteride) or AR inhibitors (bicalutamide, flutamide, nilutamide, cyproterone acetate) within 28 days before randomisation.
6. Prior chemotherapy or immunotherapy for prostate cancer, except adjuvant/neoadjuvant treatment, completed > 2 years before randomisation.
7. Use of systemic corticosteroid with dose greater than the equivalent 10 mg of prednisone/day within 28 days before randomisation.
8. Radiation therapy (external beam radiation therapy [EBRT], brachytherapy, or radiopharmaceuticals) within 12 weeks before randomisation.
9. Severe or uncontrolled concurrent disease, infection or co-morbidity that, in the opinion of the investigator, would make the patient inappropriate for enrolment.
10. Initiation of treatment with bisphosphonate or denosumab within 12 weeks before randomisation. Patients receiving bone loss prevention treatment on a stable dose of e.g. bisphosphonate or denosumab for at least 28 days before randomisation can continue the
treatment during the study.
11. Known hypersensitivity to the study treatment or any of its ingredients.
12. Major surgery within 28 days before randomisation.
13. Any of the following within 6 months before randomisation: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft; congestive heart failure New York Heart Association (NYHA) Class III or IV.
14. Uncontrolled hypertension as indicated by a resting systolic BP >=160 mmHg or diastolic BP >=100 mmHg at screening. Patients may be re-screened after adjustments of antihypertensive medications.
15. Prior malignancy. Adequately treated basal cell or squamous cell carcinoma of skin or superficial bladder cancer that has not spread behind the connective tissue layer (i.e. pTis, pTa, and pT1) is allowed, as well as any other cancer for which chemotherapy has been completed >=5 years ago and from which the patient has been disease-free.
16. Gastrointestinal disorder or procedure which expects to interfere significantly with absorption of study treatment.
17. Active viral hepatitis, active human immunodeficiency virus (HIV) or chronic liver disease.
18. Participation in another interventional clinical trial and any concurrent treatment with any investigational drug within 28 days before randomisation.
19. Any condition that in the opinion of the investigator would impair the patients’ ability to comply with the study procedures.
20. Unable to swallow study medications and comply with study requirements.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this study is to demonstrate the superiority of ODM-201 vs. placebo in metastasis free survival (MFS) in patients with high-risk nmCRPC;Secondary Objective: The secondary objectives of this study are to demonstrate the benefit of ODM-201 for:<br>Overal survival (OS), time to first symptomatic skeletal related event (SSE), time to initiation of first cytotoxic chemotherapy for prostate cancer, time to pain progression and<br>to characterise the safety and tolerability of ODM-201;Primary end point(s): The primary efficacy variable is metastasis free survival (MFS), defined as time between randomisation and evidence of metastasis or death from any cause, whichever occurs first;Timepoint(s) of evaluation of this end point: Will be evaluated at about 572 events
- Secondary Outcome Measures
Name Time Method