Details

Details

Title 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 (ARAMIS)

IRB OCOP1814

CC 14-1317

Hospital Main Campus

Phase Phase 3

Disease Prostate

Drug ODM-201

Description

Description

Primary Objective
  • To demonstrate the superiority of ODM-201 vs. placebo in MFS in patients with high-risk nmCRPC.
Secondary Objectives
  • To demonstrate the benefit of ODM-201 for:
    • OS,
    • time to first SSE,
    • time to initiation of first cytotoxic chemotherapy for prostate cancer, and
    • time to pain progression and to characterise the safety and tolerability of ODM-201.
Additional Objectives
  • To determine benefit of ODM- 201 for:
    • progression-free survival (PFS),
    • time to first prostate cancer-related invasive procedure,
    • time to initiation of first subsequent antineoplastic therapy and to determine effect of ODM-201 on
    • PSA progression and PSA response,
    • ECOG performance status and
    • health-related QoL, to evaluate PK of ODM-201 and ORM-15341, and to explore possible relationships between exposure and safety and efficacy response.
Inclusion Criteria

Inclusion Criteria

  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. CRPC defined as 3 rising PSA levels at least 1 week apart during ADT. 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 (1.5x109/l), platelet count ≥ 100,000/μl (100x109/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 ≤ 1.5 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 and refrain from sperm donation during the study treatment and for 3 months after the end of the study treatment.
Exclusion Criteria

Exclusion Criteria

  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-α 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. Treatment with an osteoclast-targeted therapy (bisphosphonate or denosumab) to prevent skeletal-related events within 12 weeks before randomisation. Patients receiving osteoclasttargeted therapy to prevent bone loss at a dose and schedule indicated for osteoporosis may continue treatment at the same dose and schedule.
  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.
  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.