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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
Sponsor:
Collaborators:
Astellas Pharma Inc
Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Information provided by (Responsible Party):
Pfizer

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.

Condition or disease Intervention/treatment Phase
Castration-Resistant Prostate Cancer Drug: Enzalutamide Drug: Placebo Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1199 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : September 30, 2009
Actual Primary Completion Date : September 15, 2011
Actual Study Completion Date : November 2, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Enzalutamide
Formerly MDV3100
Drug: Enzalutamide
MDV3100, 160 mg orally per day
Other Names:
  • MDV3100
  • Xtandi

Placebo Comparator: Placebo Drug: Placebo
Placebo comparator




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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).

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.


Other Outcome Measures:
  1. 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.

  2. 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.

  3. 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.

  4. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00974311


  Show 249 Study Locations
Sponsors and Collaborators
Pfizer
Astellas Pharma Inc
Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Investigators
Study Director: Pfizer Pfizer CT.gov Call Center Pfizer

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00974311     History of Changes
Other Study ID Numbers: CRPC2
2009-013174-41 ( EudraCT Number )
C3431010 ( Other Identifier: Alias Study Number )
First Posted: September 10, 2009    Key Record Dates
Results First Posted: October 30, 2012
Last Update Posted: December 11, 2018
Last Verified: November 2018

Keywords provided by Pfizer:
Prostate Cancer
Castration-resistant

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action