TriangleNCT00974311 · CITED IN SOURCE DOCUMENTS
Safety and Efficacy Study of MDV3100 in Patients With Castration-Resistant Prostate Cancer Who Have Been Previously Treated With Docetaxel-based Chemotherapy
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2018-12-11
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Overall Survival
Radiographic Progression-free Survival
Time to First Skeletal-related Event
Percentage of Participants Who Were Responders for Functional Assessment of Cancer Therapy-Prostate (FACT-P)
Time to Prostate-specific Antigen (PSA) Progression
Percentage of Participants With Pain Palliation
Percentage of Participants With Prostate Specific Antigen (PSA) Response
Percentage of Participants With Soft-tissue Objective Response
European Quality of Life Five-Domain (EQ-5D) Scale
Percentage of Participants With Circulating Tumor Cell (CTC) Conversion
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Number of Participants With Clinically Significant Changes in Vital Signs
Number of Participants With Any Newly Clinically Significant Abnormal Finding in Electrocardiogram (ECG)
Number of Participants With Grade 3/4 Post-Baseline Laboratory Toxicity (Hematology and Chemistry)
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility 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
- gender Based
- true
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- MALE
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Formerly MDV3100
- intervention Names
- Drug: Enzalutamide
- label
- Enzalutamide
- type
- EXPERIMENTAL
- intervention Names
- Drug: Placebo
- label
- Placebo
- type
- PLACEBO_COMPARATOR
- interventions
- arm Group Labels
- Enzalutamide
- description
- MDV3100, 160 mg orally per day
- name
- Enzalutamide
- other Names
- MDV3100
- Xtandi
- type
- DRUG
- arm Group Labels
- Placebo
- description
- Placebo comparator
- name
- Placebo
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- TRIPLE
- who Masked
- PARTICIPANT
- INVESTIGATOR
- OUTCOMES_ASSESSOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 1199
- type
- ACTUAL
Registered outcome plans (not posted results)
- other Outcomes
- description
- 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.
- measure
- 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)
- description
- 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.
- measure
- 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)
- description
- 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.
- measure
- 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)
- description
- 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.
- measure
- 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)
- primary Outcomes
- description
- 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).
- measure
- Overall Survival
- time Frame
- During study period (up to 101 months)
- secondary Outcomes
- description
- 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.
- measure
- Radiographic Progression-free Survival
- time Frame
- During DB phase (up to 24 months)
- description
- 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.
- measure
- Time to First Skeletal-related Event
- time Frame
- During DB Phase (up to 24 months)
- description
- 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.
- measure
- Percentage of Participants Who Were Responders for Functional Assessment of Cancer Therapy-Prostate (FACT-P)
- time Frame
- Baseline up to 24 months
- description
- 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).
- measure
- 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)
- description
- 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.
- measure
- Percentage of Participants With Pain Palliation
- time Frame
- Baseline up to 24 months
- description
- 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.
- measure
- Percentage of Participants With Prostate Specific Antigen (PSA) Response
- time Frame
- During DB phase (up to 24 months)
- description
- 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.
- measure
- Percentage of Participants With Soft-tissue Objective Response
- time Frame
- During DB phase (up to 24 months)
- description
- 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.
- measure
- European Quality of Life Five-Domain (EQ-5D) Scale
- time Frame
- Week 13
- description
- 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.
- measure
- Percentage of Participants With Circulating Tumor Cell (CTC) Conversion
- time Frame
- Baseline up to 24 months
Full study description
- 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.
Source references
- references
- citation
- Cella D, Ganguli A, Turnbull J, Rohay J, Morlock R. US Population Reference Values for Health-Related Quality of Life Questionnaires Based on Demographics of Patients with Prostate Cancer. Adv Ther. 2022 Aug;39(8):3696-3710. doi: 10.1007/s12325-022-02204-3. Epub 2022 Jun 22.
- pmid
- 35731340
- type
- DERIVED
- citation
- Joshua AM, Armstrong A, Crumbaker M, Scher HI, de Bono J, Tombal B, Hussain M, Sternberg CN, Gillessen S, Carles J, Fizazi K, Lin P, Duggan W, Sugg J, Russell D, Beer TM. Statin and metformin use and outcomes in patients with castration-resistant prostate cancer treated with enzalutamide: A meta-analysis of AFFIRM, PREVAIL and PROSPER. Eur J Cancer. 2022 Jul;170:285-295. doi: 10.1016/j.ejca.2022.04.005. Epub 2022 May 26.
- pmid
- 35643841
- type
- DERIVED
- citation
- Zhao JL, Fizazi K, Saad F, Chi KN, Taplin ME, Sternberg CN, Armstrong AJ, de Bono JS, Duggan WT, Scher HI. The Effect of Corticosteroids on Prostate Cancer Outcome Following Treatment with Enzalutamide: A Multivariate Analysis of the Phase III AFFIRM Trial. Clin Cancer Res. 2022 Mar 1;28(5):860-869. doi: 10.1158/1078-0432.CCR-21-1090.
- pmid
- 34965947
- type
- DERIVED
- citation
- Tombal BF, Freedland SJ, Armstrong AJ, Beer TM, Stenzl A, Sternberg CN, Hussain M, Ganguli A, Ramaswamy K, Bhadauria H, Ivanescu C, Turnbull J, Holmstrom S, Saad F. Impact of enzalutamide on patient-reported fatigue in patients with prostate cancer: data from the pivotal clinical trials. Prostate Cancer Prostatic Dis. 2022 Feb;25(2):288-295. doi: 10.1038/s41391-021-00447-9. Epub 2021 Sep 13.
- pmid
- 34518652
- type
- DERIVED
- citation
- Armstrong AJ, Al-Adhami M, Lin P, Parli T, Sugg J, Steinberg J, Tombal B, Sternberg CN, de Bono J, Scher HI, Beer TM. Association Between New Unconfirmed Bone Lesions and Outcomes in Men With Metastatic Castration-Resistant Prostate Cancer Treated With Enzalutamide: Secondary Analysis of the PREVAIL and AFFIRM Randomized Clinical Trials. JAMA Oncol. 2020 Feb 1;6(2):217-225. doi: 10.1001/jamaoncol.2019.4636.
- pmid
- 31830211
- type
- DERIVED
- citation
- Poon DMC, Wong KCW, Chan TW, Law K, Chan K, Lee EKC, Lee C, Chan M; Hong Kong Society of Uro-Oncology (HKSUO). Survival Outcomes, Prostate-specific Antigen Response, and Tolerance in First and Later Lines of Enzalutamide Treatment for Metastatic Castration-resistant Prostate Cancer: A Real-World Experience in Hong Kong. Clin Genitourin Cancer. 2018 Oct;16(5):402-412.e1. doi: 10.1016/j.clgc.2018.07.008. Epub 2018 Jul 21.
- pmid
- 30126765
- type
- DERIVED
- citation
- Heller G, McCormack R, Kheoh T, Molina A, Smith MR, Dreicer R, Saad F, de Wit R, Aftab DT, Hirmand M, Limon A, Fizazi K, Fleisher M, de Bono JS, Scher HI. Circulating Tumor Cell Number as a Response Measure of Prolonged Survival for Metastatic Castration-Resistant Prostate Cancer: A Comparison With Prostate-Specific Antigen Across Five Randomized Phase III Clinical Trials. J Clin Oncol. 2018 Feb 20;36(6):572-580. doi: 10.1200/JCO.2017.75.2998. Epub 2017 Dec 22.
- pmid
- 29272162
- type
- DERIVED
- citation
- Antoun S, Bayar A, Ileana E, Laplanche A, Fizazi K, di Palma M, Escudier B, Albiges L, Massard C, Loriot Y. High subcutaneous adipose tissue predicts the prognosis in metastatic castration-resistant prostate cancer patients in post chemotherapy setting. Eur J Cancer. 2015 Nov;51(17):2570-7. doi: 10.1016/j.ejca.2015.07.042. Epub 2015 Aug 13.
- pmid
- 26278649
- type
- DERIVED
- citation
- Gibbons JA, Ouatas T, Krauwinkel W, Ohtsu Y, van der Walt JS, Beddo V, de Vries M, Mordenti J. Clinical Pharmacokinetic Studies of Enzalutamide. Clin Pharmacokinet. 2015 Oct;54(10):1043-55. doi: 10.1007/s40262-015-0271-5.
- pmid
- 25917876
- type
- DERIVED
- citation
- Cella D, Ivanescu C, Holmstrom S, Bui CN, Spalding J, Fizazi K. Impact of enzalutamide on quality of life in men with metastatic castration-resistant prostate cancer after chemotherapy: additional analyses from the AFFIRM randomized clinical trial. Ann Oncol. 2015 Jan;26(1):179-185. doi: 10.1093/annonc/mdu510. Epub 2014 Oct 30.
- pmid
- 25361992
- type
- DERIVED
- citation
- Saad F, de Bono J, Shore N, Fizazi K, Loriot Y, Hirmand M, Franks B, Haas GP, Scher HI. Efficacy outcomes by baseline prostate-specific antigen quartile in the AFFIRM trial. Eur Urol. 2015 Feb;67(2):223-30. doi: 10.1016/j.eururo.2014.08.025. Epub 2014 Aug 27.
- pmid
- 25171902
- type
- DERIVED
- citation
- Merseburger AS, Scher HI, Bellmunt J, Miller K, Mulders PF, Stenzl A, Sternberg CN, Fizazi K, Hirmand M, Franks B, Haas GP, de Bono J, de Wit R. Enzalutamide in European and North American men participating in the AFFIRM trial. BJU Int. 2015 Jan;115(1):41-9. doi: 10.1111/bju.12898. Epub 2014 Oct 23.
- pmid
- 25123978
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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- six randomized, multicenter clinical trials. Patients received concomitant GnRH therapy or had prior bilateral orchiectomy, unless otherwise indicated. AFFIRM (NCT00974311): XTANDI versus Placebo in Metastatic CRPC Following Chemotherapy In AFFIRM, a total of 1199 patients who had received prior docetaxel-based chemotherapy were
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Preserved source evidence · Not medical advice