Safety and Efficacy Study of MDV3100 in Patients With Castration-Resistant Prostate Cancer Who Have Been Previously Treated With Docetaxel-based Chemotherapy

Study Overview
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Brief Summary
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This is a phase 3 study to compare the clinical benefit of MDV3100 versus placebo in patients with castration-resistant prostate cancer who have been previously treated with docetaxel-based chemotherapy.

Official Title
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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

Conditions
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Castration-Resistant Prostate Cancer

Intervention / Treatment
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* Drug: Enzalutamide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Progressive prostate cancer Medical or surgical castration with testosterone less than 50 ng/dl One or two prior chemotherapy regimens. At least one chemotherapy regimen must have contained docetaxel Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Adequate bone marrow, hepatic, and renal function Able to swallow the study drug and comply with study requirements Informed consent Exclusion Criteria: Metastases in the brain or active epidural disease Another malignancy within the previous 5 years Clinically significant cardiovascular disease Gastrointestinal disorder affecting absorption

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enzalutamide<br>Formerly MDV3100 | Drug: Enzalutamide<br>* MDV3100, 160 mg orally per day<br>* Other names: Xtandi;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Survival was defined as time from randomization to death due to any cause. The duration of overall survival was right-censored for participants who were lost to follow-up since randomization or not known to have died at the data analysis cut-off date (this included participants who were known to have died after the data analysis cut-off date). | During study period (up to 101 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic Progression-free Survival | Radiographic progression-free survival was defined as time from randomization to the earliest objective evidence of radiographic progression or death due to any cause. Participants were assessed for objective disease progression at regularly scheduled visits. The consensus guidelines of the Prostate Cancer Clinical Trials Working Group 2 were taken into consideration for the determination of disease progression. Radiographic disease progression was defined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 for soft tissue disease, or the appearance of two or more new bone lesions on bone scan. Progression at the first scheduled reassessment at Week 13 required a confirmatory scan 6 or more weeks later. Participants who did not reach the endpoint were right censored at their last assessment. | During DB phase (up to 24 months) | 
| Time to First Skeletal-related Event | The time to first skeletal-related event was defined as time from randomization to the occurrence of the first skeletal-related event. Participants were assessed for skeletal-related events at regularly scheduled visits. A skeletal-related event was defined as radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression, or change of antineoplastic therapy to treat bone pain. Participants who did not reach the endpoint were right censored at their last assessment. | During DB Phase (up to 24 months) | 
| Percentage of Participants Who Were Responders for Functional Assessment of Cancer Therapy-Prostate (FACT-P) | The FACT-P was a 39-item participant questionnaire which assessed physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and additional prostate cancer specific concerns (12 items). All items were scored from 0 (not at all) to 4 (very much). The sum of scores on all 5 domains constitutes the global FACT-P. The global/total FACT-P score ranged from 0 (worst) to 156 (best), higher scores indicate better health status. Responders were those participants who had a 10-point improvement in their total FACT-P score, as compared with baseline, on two consecutive measurements obtained at least 3 weeks apart. | Baseline up to 24 months | 
| Time to Prostate-specific Antigen (PSA) Progression | Time to PSA progression was defined as time from randomization to PSA progression. Participants who did not reach the endpoint were right censored at their last assessment or for participants with no post-baseline PSA assessment, date of randomization. For participants with PSA declines at Week 13, the PSA progression date was defined as the date that a >=25% increase and an absolute increase of >=2 nanogram per milliliter (ng/mL) above the nadir was documented, which was confirmed by a second consecutive value obtained 3 or more weeks later (required only if PSA progression did not occur at last PSA assessment). For participants with no PSA declines at Week 13, PSA progression date was defined as the date that a >=25% increase and an absolute increase of >=2 ng/mL above the baseline was documented, which was confirmed by a second consecutive value 3 or more weeks later (required only if PSA progression did not occur at last PSA assessment). | Baseline and at every study visit from Week 13 while on study drug (up to 24 months) | 
| Percentage of Participants With Pain Palliation | The proportion of participants with pain palliation was assessed for participants with a stable and sufficient pain burden at study entry. Pain burden was measured by question #3 of the Brief Pain Inventory (Short Form). This scale measures pain on a 0 to 10 scale with 0 indicating no pain and 10 indicating pain as bad as you can imagine. Pain palliation at Week 13 was determined for the proportion of men with baseline bone metastasis(es) who had baseline pain attributable to the metastasis(es). Palliation was defined as >=30% reduction in average pain score at Week 13 compared to baseline without a >=30% increase in analgesic use. | Baseline up to 24 months | 
| Percentage of Participants With Prostate Specific Antigen (PSA) Response | Participants were evaluable for PSA response rate if they had a PSA level measured at baseline and at least 1 post-baseline assessment. Both PSA responses of > 50% and > 90% were determined. PSA responses required confirmation with a subsequent assessment that was conducted at least 3 weeks later. | During DB phase (up to 24 months) | 
| Percentage of Participants With Soft-tissue Objective Response | The best overall soft tissue response as assessed using RECIST v1.1 during the study was summarized using the investigators' response assessments and also the derived response assessments by treatment group. Only participants with measurable soft tissue disease at screening were included in this analysis. Participants with measurable disease at screening are participants who had at least 1 target lesion identified per RECIST v1.1 at screening. Percentage of participants summarizes the number of participants with complete or partial objective response (%). Soft Tissue assessment based on Eisenhauer EA, Therasse P, Bogaerts J et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45:228-247. | During DB phase (up to 24 months) | 
| European Quality of Life Five-Domain (EQ-5D) Scale | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility or index score. Five parameters (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) were assessed on 3-point categorical scale (1= no problems, 2= some/moderate problems and 3= severe problem). Score were transformed and resulted in a total EQ-5D score range of 0 (worst imaginable health state) to 100 (best imaginable health state), with higher scores indicating better health and quality of life. | Week 13 | 
| Percentage of Participants With Circulating Tumor Cell (CTC) Conversion | CTC conversion was assessed for participants with baseline CTC counts of greater than or equal to (>=) 5 cells per 7.5 milliliter (mL) of blood. A CTC conversion was defined as a decline in the CTC count to less than (<) 5 cells per 7.5 mL of blood. In this outcome measure percentage of participants with CTC conversion was reported. | Baseline up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate Cancer, Castration-resistant