AFFIRM: A Multinational Phase 3, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Oral MDV3100 in Patients with Progressive Castration-Resistant Prostate Cancer Previously Treated with Docetaxel-Based Chemotherapy - AFFIRM

Phase 1

• Conditions: Patients with progressive castration-resistant prostate cancer previously treated with doxetaxel-based chemotherapy; MedDRA version: 12.0Level: PTClassification code 10060862Term: Prostate cancer

• Registration Number: EUCTR2009-013174-41-FR
• Lead Sponsor: Medivation, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-09-25
• Last Update Posted: 29 January 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 1170

Inclusion Criteria

1. Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features;
2. Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration);
3. For patients who have not had an orchiectomy, there must be a plan to maintain effective GnRH-analogue therapy for the duration of the trial;
4. Serum testosterone level < 1.7 nmol/L (50 ng/dL) at the Screening visit;
5. Patients receiving bisphosphonate therapy must have been on stable doses for at least four weeks;
6. Progressive disease by PSA or imaging after docetaxel-based chemotherapy in the setting of medical or surgical castration. Disease progression for study entry is defined as one or more of the following three criteria:
• PSA progression defined by a minimum of three rising PSA levels with an interval of = 1 week between each determination. The PSA value at the Screening visit should be = 2 µg/L (2 ng/mL);
• Soft tissue disease progression defined by RECIST 1.1 (Appendix A);
• Bone disease progression defined by two or more new lesions on bone scan;
7. No more than two prior chemotherapy regimens with at least one regimen containing docetaxel;
8. ECOG performance status of 0–2;
9. Estimated life expectancy of = 6 months;
10. Able to swallow the study drug and comply with study requirements;
11. Willing and able to give informed consent.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Severe concurrent disease, infection, or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrollment;
2. Metastases in the brain or active epidural disease (NOTE: patients with treated epidural disease are allowed);
3. Absolute neutrophil count < 1,500/µL, platelet count < 100,000/µL, and hemoglobin < 5.6 mmol/L (9 g/dL) at the Screening visit; (NOTE: patients may not have received any growth factors or blood transfusions within 7 days of the hematologic laboratory values obtained at the Screening visit);
4. Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 times the upper limit of normal at the Screening visit;
5. Creatinine > 177 µmol/L (2 mg/dL) at the Screening visit;
6. Albumin < 30 g/L (3.0 g/dL) at the Screening visit;
7. History of another malignancy within the previous 5 years other than curatively treated non-melanomatous skin cancer;
8. Treatment with androgen receptor antagonists (bicalutamide, flutamide, nilutamide), 5-a reductase inhibitors (finasteride, dutasteride), estrogens, or chemotherapy within four weeks of enrollment (Day 1 visit) or plans to initiate treatment with any of these treatments during the study;
9. Treatment with therapeutic immunizations for prostate cancer (e.g., PROVENGE®) or plans to initiate treatment with any of these treatments during the study;
10. Use of herbal products that may decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of prednisone/prednisolone per day within four weeks of enrollment (Day 1 visit) or plans to initiate treatment with any of these treatments during the study;
11. History of prostate cancer progression on ketoconazole or plans to initiate ketoconazole treatment during the study;
12. Radiation therapy within 3 weeks (if single fraction of radiotherapy within 2 weeks) and radionuclide therapy within 8 weeks of enrollment (Day 1 visit);
13. Planned palliative procedures for alleviation of bone pain such as radiation therapy or surgery;
14. Structurally unstable bone lesions suggesting impending fracture;
15. History of seizure, including any febrile seizure, loss of consciousness, or transient ischemic attack within 12 months of enrollment (Day 1 visit), or any condition that may pre-dispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization);
16. Clinically significant cardiovascular disease;
17. Have used or plan to use from 30 days prior to enrollment (Day 1 visit) through the end of the study medications known to lower the seizure threshold or prolong the QT interval;
• Aminophylline/theophylline;
• Atypical antipsychotics (e.g., clozapine, olanzapine, risperidone, ziprasidone);
• Bupropion;
• Class IA and III antiarrhythmics (e.g., amiodarone, bretylium, disopyramide, ibutilide, procainamide, quinidine, sotalol);
• Dolasetron;
• Droperidol;
• Gatafloxacin/moxifloxacin;
• Insulin;
• Lithium;
• Macrolide antibiotics (e.g., erythromycin, clarithromycin);
• Pethidine;
• Phenothiazine antipsychotics (e.g., chlorpromazine, mesoridazine, thioridazine);
• Pimozide;
• Tricyclic and tetracyclic antidepressants (e.g., amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine);
• Venlafaxine.
18. Participation in a previous clinical trial of an investigational agent that blocks androgen synthesis (e.g., abiraterone acetate, TAK-700, TAK-68

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified