Trial Outcomes & Findings for Determine Effect of Enzalutamide (MDV3100) on the Androgen Signaling Pathway in Correlation With the Anti-tumor Effects of Enzalutamide (NCT NCT01091103)

NCT ID: NCT01091103

Last Updated: 2018-10-23

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

60 participants

Primary outcome timeframe

Baseline, Week 9

Results posted on

2018-10-23

Participant Flow

Single center clinical trial

Participant milestones

Participant milestones
Measure	Enzalutamide Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.
Overall Study STARTED	60
Overall Study COMPLETED	56
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Enzalutamide Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.
Overall Study Adverse Event	1
Overall Study Progressive Disease	3

Baseline Characteristics

Determine Effect of Enzalutamide (MDV3100) on the Androgen Signaling Pathway in Correlation With the Anti-tumor Effects of Enzalutamide

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Enzalutamide n=60 Participants Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.
Age, Continuous	67.9 years STANDARD_DEVIATION 9.99 • n=5 Participants
Age, Customized < 55	6 years n=5 Participants
Age, Customized 55 to < 65	17 years n=5 Participants
Age, Customized 65 to < 75	18 years n=5 Participants
Age, Customized >= 75	19 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	60 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 9

Population: Participants who received any amount of enzalutamide and had bone marrow testosterone measurements at baseline and at least 1 post-baseline assessment. Note that the documentation of bone marrow involvement with cancer was not required.

Outcome measures

Outcome measures
Measure	Enzalutamide n=31 Participants Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Enzalutamide, PSA Non-Responders at Week 9 PSA non-responders are defined by a less than 50% reduction from baseline in PSA at Week 9
Change From Baseline in Bone Marrow Testosterone	0.05 ng/mL Standard Deviation 0.072	—

PRIMARY outcome

Timeframe: Baseline, Week 9

Population: Participants who received any amount of enzalutamide and had bone marrow dihydrotestosterone measurements at baseline and at least 1 post-baseline assessment. Note that the documentation of bone marrow involvement with cancer was not required.

Outcome measures

Outcome measures
Measure	Enzalutamide n=31 Participants Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Enzalutamide, PSA Non-Responders at Week 9 PSA non-responders are defined by a less than 50% reduction from baseline in PSA at Week 9
Change From Baseline in Bone Marrow Dihydrotestosterone	0.00 ng/mL Standard Deviation 0.022	—

PRIMARY outcome

Timeframe: Baseline, Week 9

Bone marrow biopsies were performed at the Day 1 visit prior to initiation of enzalutamide administration. Repeat bone marrow biopsies were performed at the Week 9 visit. If a repeat bone marrow was not performed at the Week 9 visit or if a patient discontinued the study before the Week 9 visit, a bone marrow biopsy was obtained at the Safety Follow-up visit. Assessment of intratumoral testosterone was assessed by liquid chromatography mass spectrometry. Serum samples for measurement of PSA levels were obtained at baseline prior to initiation of enzalutamide administration and at the Week 9 visit. The change from baseline in bone marrow testosterone levels at Week 9 was correlated with PSA response status at Week 9.

Outcome measures

Outcome measures
Measure	Enzalutamide n=13 Participants Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Enzalutamide, PSA Non-Responders at Week 9 n=18 Participants PSA non-responders are defined by a less than 50% reduction from baseline in PSA at Week 9
Change From Baseline in Bone Marrow Testosterone at Week 9 by Prostate-Specific Antigen (PSA) Response Status	0.05 ng/mL Standard Deviation 0.107	0.05 ng/mL Standard Deviation 0.034

PRIMARY outcome

Timeframe: Baseline, Week 9

Bone marrow biopsies were performed at the Day 1 visit prior to initiation of enzalutamide administration. Repeat bone marrow biopsies were performed at the Week 9 visit. If a repeat bone marrow was not performed at the Week 9 visit or if a patient discontinued the study before the Week 9 visit, a bone marrow biopsy was obtained at the Safety Follow-up visit. Assessment of intratumoral dihydrotestosterone was assessed by liquid chromatography mass spectrometry. Serum samples for measurement of PSA levels were obtained at baseline prior to initiation of enzalutamide administration and at the Week 9 visit. The change from baseline in bone marrow dihydrotestosterone levels at Week 9 was correlated with PSA response status at Week 9.

Outcome measures

Outcome measures
Measure	Enzalutamide n=13 Participants Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Enzalutamide, PSA Non-Responders at Week 9 n=18 Participants PSA non-responders are defined by a less than 50% reduction from baseline in PSA at Week 9
Change From Baseline in Bone Marrow Dihydrotestosterone at Week 9 by Prostate-Specific Antigen (PSA) Response Status	-0.01 ng/mL Standard Deviation 0.034	0.00 ng/mL Standard Deviation 0.000

SECONDARY outcome

Timeframe: Baseline, Week 9

Population: Participants who received any amount of enzalutamide and had PSA values at baseline and at the Week 9 Visit.

Serum samples for measurement of PSA levels were obtained at baseline prior to initiation of enzalutamide administration and at the Week 9 visit.

Outcome measures

Outcome measures
Measure	Enzalutamide n=56 Participants Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Enzalutamide, PSA Non-Responders at Week 9 PSA non-responders are defined by a less than 50% reduction from baseline in PSA at Week 9
Percentage of Participants at Week 9 With a Response in Prostate-Specific Antigen (PSA) >=50% Reduction in PSA from Baseline	41.1 percentage of participants Interval 28.1 to 55.0	—
Percentage of Participants at Week 9 With a Response in Prostate-Specific Antigen (PSA) >=90% Reduction in PSA from Baseline	21.4 percentage of participants Interval 11.6 to 34.4	—

SECONDARY outcome

Timeframe: Duration of study treatment through the data cutoff, up to 3 years.

Population: All participants who received any amount of enzalutamide. Fifteen (25.0%) participants were still on study drug as of the data cutoff date and were censored at the data cutoff date.

Exposure to study drug through the data cutoff of 26AUG2011 only. Fifteen participants (25.0%) were still on study drug as of the data cut-off date and were censored at this date.

Outcome measures

Outcome measures
Measure	Enzalutamide n=60 Participants Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Enzalutamide, PSA Non-Responders at Week 9 PSA non-responders are defined by a less than 50% reduction from baseline in PSA at Week 9
Median Time to Study Drug Discontinuation	5.0 months Interval 3.6 to 6.0	—

SECONDARY outcome

Timeframe: Baseline, Week 5

Population: Participants who received any amount of enzalutamide and had urinary N-telopeptide measurements at baseline and at Week 5.

Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 5.

Outcome measures

Outcome measures
Measure	Enzalutamide n=59 Participants Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Enzalutamide, PSA Non-Responders at Week 9 PSA non-responders are defined by a less than 50% reduction from baseline in PSA at Week 9
Change From Baseline in Urinary N-Telopeptide	34.81 mmol/mmol creatinine Standard Deviation 137.361	—

SECONDARY outcome

Timeframe: Baseline, Week 9

Population: Participants who received any amount of enzalutamide and had urinary N-telopeptide measurements at baseline and at Week 9.

Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 9.

Outcome measures

Outcome measures
Measure	Enzalutamide n=55 Participants Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Enzalutamide, PSA Non-Responders at Week 9 PSA non-responders are defined by a less than 50% reduction from baseline in PSA at Week 9
Change From Baseline in Urinary N-Telopeptide	205.84 mmol/mmol creatinine Standard Deviation 1334.820	—

SECONDARY outcome

Timeframe: Baseline, Week 17

Population: Participants who received any amount of enzalutamide and had urinary N-telopeptide measurements at baseline and at Week 17.

Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 17.

Outcome measures

Outcome measures
Measure	Enzalutamide n=39 Participants Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Enzalutamide, PSA Non-Responders at Week 9 PSA non-responders are defined by a less than 50% reduction from baseline in PSA at Week 9
Change From Baseline in Urinary N-Telopeptide	-0.92 mmol/mmol creatinine Standard Deviation 205.941	—

SECONDARY outcome

Timeframe: Baseline, Week 25

Population: Participants who received any amount of enzalutamide and had urinary N-telopeptide measurements at baseline and at Week 25.

Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 25.

Outcome measures

Outcome measures
Measure	Enzalutamide n=27 Participants Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Enzalutamide, PSA Non-Responders at Week 9 PSA non-responders are defined by a less than 50% reduction from baseline in PSA at Week 9
Change From Baseline in Urinary N-Telopeptide	-18.96 mmol/mmol creatinine Standard Deviation 278.112	—

SECONDARY outcome

Timeframe: Baseline, Week 33

Population: Participants who received any amount of enzalutamide and had urinary N-telopeptide measurements at baseline and at Week 33.

Outcome measures

Outcome measures
Measure	Enzalutamide n=14 Participants Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Enzalutamide, PSA Non-Responders at Week 9 PSA non-responders are defined by a less than 50% reduction from baseline in PSA at Week 9
Change From Baseline in Urinary N-Telopeptide	-89.36 mmol/mmol creatinine Standard Deviation 363.140	—

SECONDARY outcome

Timeframe: Baseline, Week 41

Population: Participants who received any amount of enzalutamide and had urinary N-telopeptide measurements at baseline and at Week 41.

Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 41.

Outcome measures

Outcome measures
Measure	Enzalutamide n=11 Participants Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Enzalutamide, PSA Non-Responders at Week 9 PSA non-responders are defined by a less than 50% reduction from baseline in PSA at Week 9
Change From Baseline in Urinary N-Telopeptide	-2.00 mmol/mmol creatinine Standard Deviation 22.414	—

SECONDARY outcome

Timeframe: Baseline, Week 49

Population: Participants who received any amount of enzalutamide and had urinary N-telopeptide measurements at baseline and at Week 49.

Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 49.

Outcome measures

Outcome measures
Measure	Enzalutamide n=11 Participants Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Enzalutamide, PSA Non-Responders at Week 9 PSA non-responders are defined by a less than 50% reduction from baseline in PSA at Week 9
Change From Baseline in Urinary N-Telopeptide	-2.36 mmol/mmol creatinine Standard Deviation 26.526	—

SECONDARY outcome

Timeframe: Baseline, Week 57

Population: Participants who received any amount of enzalutamide and had urinary N-telopeptide measurements at baseline and at Week 57.

Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 57.

Outcome measures

Outcome measures
Measure	Enzalutamide n=6 Participants Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Enzalutamide, PSA Non-Responders at Week 9 PSA non-responders are defined by a less than 50% reduction from baseline in PSA at Week 9
Change From Baseline in Urinary N-Telopeptide	-9.33 mmol/mmol creatinine Standard Deviation 37.824	—

SECONDARY outcome

Timeframe: Baseline, Week 65

Population: Participants who received any amount of enzalutamide and had urinary N-telopeptide measurements at baseline and at Week 65.

Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 65.

Outcome measures

Outcome measures
Measure	Enzalutamide n=6 Participants Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.	Enzalutamide, PSA Non-Responders at Week 9 PSA non-responders are defined by a less than 50% reduction from baseline in PSA at Week 9
Change From Baseline in Urinary N-Telopeptide	17.67 mmol/mmol creatinine Standard Deviation 17.131	—

Adverse Events

Enzalutamide

Serious events: 13 serious events

Other events: 59 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Enzalutamide n=60 participants at risk Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.
Cardiac disorders Angina pectoris	1.7% 1/60
Cardiac disorders Bundle branch block left	1.7% 1/60
Cardiac disorders Myocardial infarction	1.7% 1/60
Cardiac disorders Sinus bradycardia	1.7% 1/60
Gastrointestinal disorders Small intestinal obstruction	1.7% 1/60
General disorders Fatigue	1.7% 1/60
Infections and infestations Urinary tract infection	3.3% 2/60
Infections and infestations Urosepsis	3.3% 2/60
Infections and infestations Periorbital cellulitis	1.7% 1/60
Injury, poisoning and procedural complications Fall	1.7% 1/60
Injury, poisoning and procedural complications Incisional hernia	1.7% 1/60
Injury, poisoning and procedural complications Postoperative wound complication	1.7% 1/60
Musculoskeletal and connective tissue disorders Back pain	1.7% 1/60
Nervous system disorders Embolic stroke	1.7% 1/60
Nervous system disorders Third nerve disorder	1.7% 1/60
Nervous system disorders Spinal cord compression	1.7% 1/60
Nervous system disorders Transient ischaemic attack	1.7% 1/60
Renal and urinary disorders Hydronephrosis	1.7% 1/60
Renal and urinary disorders Urinary retention	1.7% 1/60
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.7% 1/60
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.7% 1/60

Other adverse events

Other adverse events
Measure	Enzalutamide n=60 participants at risk Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.
General disorders Fatigue	71.7% 43/60
Metabolism and nutrition disorders Anorexia	28.3% 17/60
Gastrointestinal disorders Constipation	28.3% 17/60
Musculoskeletal and connective tissue disorders Arthralgia	26.7% 16/60
Musculoskeletal and connective tissue disorders Back pain	23.3% 14/60
General disorders Oedema peripheral	23.3% 14/60
Gastrointestinal disorders Nausea	18.3% 11/60
Respiratory, thoracic and mediastinal disorders Dyspnoea	16.7% 10/60
Vascular disorders Hot Flush	15.0% 9/60
Musculoskeletal and connective tissue disorders Bone pain	13.3% 8/60
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	13.3% 8/60
Nervous system disorders Dysgeusia	11.7% 7/60
Psychiatric disorders Insomnia	11.7% 7/60
Musculoskeletal and connective tissue disorders Musculoskeletal pain	11.7% 7/60
Renal and urinary disorders Pollakiuria	10.0% 6/60
Renal and urinary disorders Urinary incontinence	10.0% 6/60
Investigations Blood alkaline phosphatase increased	8.3% 5/60
Respiratory, thoracic and mediastinal disorders Cough	8.3% 5/60
Musculoskeletal and connective tissue disorders Pain in extremity	8.3% 5/60
Psychiatric disorders Depression	6.7% 4/60
Skin and subcutaneous tissue disorders Dry skin	6.7% 4/60
Nervous system disorders Headache	6.7% 4/60
Musculoskeletal and connective tissue disorders Muscle spasms	6.7% 4/60
Gastrointestinal disorders Vomiting	6.7% 4/60
Gastrointestinal disorders Abdominal pain	5.0% 3/60
Injury, poisoning and procedural complications Contusion	5.0% 3/60
Gastrointestinal disorders Dyspepsia	5.0% 3/60
Injury, poisoning and procedural complications Fall	5.0% 3/60
Respiratory, thoracic and mediastinal disorders Nasal congestion	5.0% 3/60
General disorders Pain	5.0% 3/60
Nervous system disorders Peripheral sensory neuropathy	5.0% 3/60
Skin and subcutaneous tissue disorders Rash	5.0% 3/60

Additional Information

Mohammad Hirmand, MD, VP, Clinical Development

Medivation, Inc.

Phone: 415-829-4126

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI agrees not to independently publish the results before the publication of the multi-center PI paper. Sponsor shall review and comment 30 days prior to submission or disclosure. If publication or disclosure contains Sponsor Confidential Information, other than Study Data, PI agrees to remove Confidential Information from publication or disclosure. Sponsor may request that PI delay such publication for an additional 60 days to protect the patentability of any Invention described.
Publication restrictions are in place

Restriction type: OTHER