Clinical trial NCT02125357 (phase 2, status: completed)
Conditions: metastatic castration-resistant prostate cancer
ICD codes: C61, D29.1, D40.0, Z15.03, Z80.42, Z85.46, Z12.5
Drugs: abiraterone acetate, enzalutamide
SMILES: [H][C@@]12CC=C(C3=CC=CN=C3)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC=C2C[C@@H](O)CC[C@]12C, CNC(=O)C1=C(F)C=C(C=C1)N1C(=S)N(C(=O)C1(C)C)C1=CC=C(C#N)C(=C1)C(F)(F)F
Eligibility criteria:

        Inclusion Criteria:

          1. Willing and able to provide informed consent

          2. Adult males ≥ 18 years age

          3. History of adenocarcinoma of the prostate diagnosed histologically without evidence of
             neuroendocrine or small cell differentiation

          4. Prior surgical orchiectomy or if on luteinizing hormone-releasing hormone (LHRH)
             agonist/antagonist then testosterone < 1.7 nmol/L at screening visit (patients must
             maintain LHRH agonist/antagonist therapy for duration of study treatment if not
             surgically castrated)

          5. Evidence of metastatic disease on bone scan or CT scan

          6. Evidence of biochemical or imaging progression in the setting of surgical or medical
             castration. Progressive disease for study entry is defined by one of the following
             three criteria:

               1. PSA progression: minimum of two rising PSA values from a baseline measurement
                  with an interval of ≥ 1 week between each measurement. Minimum PSA at screening
                  visit is > 2.0 ug/L

               2. Soft tissue or visceral disease progression (see Appendix B for definition of
                  measurable disease as per Response Evaluation Criteria in Solid Tumours (RECIST)
                  1.1 criteria)

               3. Bone progression: ≥ 2 new lesions on bone scan

          7. ECOG performance status 0-2 (see Appendix C)

          8. Eligible for treatment with either abiraterone acetate or enzalutamide as per standard
             of care guidelines

          9. Adequate organ function defined as:

               1. Absolute neutrophil count ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L and
                  hemoglobin ≥ 80 g/L

               2. Creatinine clearance ≥ 30 ml/min (calculated by Cockcroft-Gault formula, see
                  Appendix D)

               3. Serum potassium within normal limits

               4. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) except for patients with
                  known Gilbert's syndrome (direct bilirubin ≤ 1.5 x ULN)

               5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN

         10. Able to swallow study drug and comply with study requirements including provision of
             peripheral blood samples at specified time points for correlative studies

         11. Recovery from all prior treatment-related toxicity to grade ≤ 2 (as per Common
             Terminology Criteria for Adverse Events 4.0)

        Exclusion Criteria:

          1. Severe concurrent illness or co-morbid disease that would make the subject unsuitable
             for enrolment

          2. Prior therapy with CYP17 inhibitors (including abiraterone acetate, TAK-700, TOK-001
             and ketoconazole), enzalutamide or other experimental anti-androgens (e.g. ARN-509,
             TOK-001)

          3. Prior systemic chemotherapy for mCRPC

          4. Life expectancy < 6 months

          5. Active concurrent malignancy (with the exception of non-melanomatous skin cancer)

          6. Wide-field radiotherapy or radioisotopes such as Strontium-89 or Radium-223 ≤ 28 days
             prior to starting study drug (limited-field palliative radiotherapy for 1-5 fractions
             is permitted at anytime prior to commencement protocol therapy)

          7. Brain metastases or active epidural disease (treated epidural disease is permitted)

          8. Use of herbal products that may lower PSA level (e.g. saw palmetto)

          9. Contraindication to prednisone therapy including poorly controlled diabetes mellitus

         10. History of seizure or seizure disorder, or history of any cerebrovascular event within
             6 months of study entry.

         11. Gastrointestinal disorder affecting absorption

         12. Major surgery within 4 weeks of starting study treatment