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

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ClinicalTrials.gov Identifier: NCT00974311

Recruitment Status : Completed

First Posted : September 10, 2009

Results First Posted : October 30, 2012

Last Update Posted : December 11, 2018

View this study on the modernized ClinicalTrials.gov

Sponsor:

Collaborators:

Astellas Pharma Inc

Medivation LLC, a wholly owned subsidiary of Pfizer Inc.

Information provided by (Responsible Party):

Pfizer

Tracking Information

First Submitted Date ^ICMJE

September 9, 2009

First Posted Date ^ICMJE

September 10, 2009

Results First Submitted Date ^ICMJE

September 28, 2012

Results First Posted Date ^ICMJE

October 30, 2012

Last Update Posted Date

December 11, 2018

Actual Study Start Date ^ICMJE

September 30, 2009

Actual Primary Completion Date

September 15, 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Overall Survival [ Time Frame: During study period (up to 101 months) ]

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).

Original Primary Outcome Measures ^ICMJE

Overall survival

Change History

Current Secondary Outcome Measures ^ICMJE

Radiographic Progression-free Survival [ Time Frame: During DB phase (up to 24 months) ]
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.
Time to First Skeletal-related Event [ Time Frame: During DB Phase (up to 24 months) ]
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.
Percentage of Participants Who Were Responders for Functional Assessment of Cancer Therapy-Prostate (FACT-P) [ Time Frame: Baseline up to 24 months ]
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.
Time to Prostate-specific Antigen (PSA) Progression [ Time Frame: Baseline and at every study visit from Week 13 while on study drug (up to 24 months) ]
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).
Percentage of Participants With Pain Palliation [ Time Frame: Baseline up to 24 months ]
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.
Percentage of Participants With Prostate Specific Antigen (PSA) Response [ Time Frame: During DB phase (up to 24 months) ]
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.
Percentage of Participants With Soft-tissue Objective Response [ Time Frame: During DB phase (up to 24 months) ]
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.
European Quality of Life Five-Domain (EQ-5D) Scale [ Time Frame: Week 13 ]
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.
Percentage of Participants With Circulating Tumor Cell (CTC) Conversion [ Time Frame: Baseline up to 24 months ]
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.

Original Secondary Outcome Measures ^ICMJE

Not Provided

Current Other Pre-specified Outcome Measures

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline, up to the safety follow-up visit or unscheduled visit or the initiation of another anti-neoplastic therapy whichever occurred first (up to 101 months) ]
AE: any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE: AE resulting in any of following outcomes or deemed significant and jeopardized participants or required treatment to prevent other AE outcomes for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were events which occurred between first dose of study drug and up to the safety follow-up visit or the initiation of another anti-neoplastic therapy, whichever occurred first (up to 101 months). AEs included both serious and non-serious AEs. Clinically significant physical examination abnormalities were reported as AEs. Unscheduled visit was performed at any time during the study whenever necessary to assess for or follow-up on AEs, at the participant's request or if deemed necessary by the investigator.
Number of Participants With Clinically Significant Changes in Vital Signs [ Time Frame: Baseline, up to the safety follow-up visit or unscheduled visit or the initiation of another anti-neoplastic therapy whichever occurred first (up to 101 months) ]
Criteria for abnormalities in vital signs included: sitting/supine systolic blood pressure (SBP) values: absolute result greater than (>) 180 millimeter of mercury (mmHg) and >40 mmHg increase from baseline (BL) and less than (<) 90 mmHg and >30 mmHg decrease from BL; diastolic blood pressure (DBP) values: absolute result >105 mmHg and >30 mmHg increase from BL and absolute result < 50 mmHg and >20 mmHg decrease from BL; any abnormalities in SBP or DBP; heart rate values: absolute result > 120 beats per minute (bpm) and >30 bpm increase from BL and absolute result < 50 bpm and >20 bpm decrease from BL or any abnormalities in heart rate. Unscheduled visit was performed at any time during the study whenever necessary to assess for or follow-up on AEs, at the participant's request or if deemed necessary by the investigator.
Number of Participants With Any Newly Clinically Significant Abnormal Finding in Electrocardiogram (ECG) [ Time Frame: Baseline, up to the end of DB phase or unscheduled visit (up to 24 months) ]
Any new post baseline abnormality was defined as any abnormal ECG finding that appeared after baseline assessment which was not seen at the screening or baseline ECG assessment. Where, criteria of abnormality was QTcF interval > 470 millisecond (msec). Participants were counted once only for a specific abnormality. This outcome measure was planned to be analysed in double blind phase only. Unscheduled visit was performed at any time during the study whenever necessary to assess for or follow-up on AEs, at the participant's request or if deemed necessary by the investigator.
Number of Participants With Grade 3/4 Post-Baseline Laboratory Toxicity (Hematology and Chemistry) [ Time Frame: Baseline, up to the safety follow-up visit or unscheduled visit or the initiation of another anti-neoplastic therapy whichever occurred first (up to 101 months) ]
Laboratory parameters included hematological and chemistry parameters. Chemistry parameters included alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bilirubin, calcium, creatine kinase, creatinine, glucose, magnesium, phosphate, potassium and sodium. Hematology parameters included haemoglobin, leukocytes, lymphocytes, neutrophils and platelet. Test abnormalities were graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 as Grade 3= severe and Grade 4= life-threatening or disabling. Only categories with at least 1 participant with abnormality are reported in this outcome measure. Unscheduled visit was performed at any time during the study whenever necessary to assess for or follow-up on AEs, at the participant's request or if deemed necessary by the investigator.

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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

Brief Summary

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.

Detailed Description

Not Provided

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 3

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Condition ^ICMJE

Castration-Resistant Prostate Cancer

Intervention ^ICMJE

Drug: Enzalutamide
MDV3100, 160 mg orally per day
Other Names:
- MDV3100
- Xtandi
Drug: Placebo
Placebo comparator

Study Arms ^ICMJE

Experimental: Enzalutamide
Formerly MDV3100

Intervention: Drug: Enzalutamide
Placebo Comparator: Placebo
Intervention: Drug: Placebo

Publications *

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Completed

Actual Enrollment ^ICMJE

1199

Original Enrollment ^ICMJE

Not Provided

Actual Study Completion Date ^ICMJE

November 2, 2017

Actual Primary Completion Date

September 15, 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Sex/Gender ^ICMJE

Sexes Eligible for Study:	Male
Gender Based Eligibility:	Yes

Ages ^ICMJE

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

Argentina, Australia, Austria, Belgium, Canada, Chile, France, Germany, Italy, Netherlands, Poland, South Africa, Spain, United Kingdom, United States

Removed Location Countries

Switzerland

Administrative Information

NCT Number ^ICMJE

NCT00974311

Other Study ID Numbers ^ICMJE

CRPC2
2009-013174-41 ( EudraCT Number )
C3431010 ( Other Identifier: Alias Study Number )

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Not Provided

IPD Sharing Statement ^ICMJE

Not Provided

Current Responsible Party

Pfizer

Original Responsible Party

Mohammad Hirmand, MD / Vice President, Clinical Development, Medivation, Inc.

Current Study Sponsor ^ICMJE

Pfizer

Original Study Sponsor ^ICMJE

Medivation, Inc.

Collaborators ^ICMJE

Astellas Pharma Inc
Medivation LLC, a wholly owned subsidiary of Pfizer Inc.

Investigators ^ICMJE

Study Director:

Pfizer Pfizer CT.gov Call Center

Pfizer

PRS Account

Pfizer

Verification Date

November 2018

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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