Metastatic Progressive Castration-resistant Prostate Cancer
Conditions
Brief summary
This study is being conducted to determine the effect of enzalutamide on the androgen signaling pathway in correlation with the anti-tumor effects of enzalutamide to identify potential predictors of response or resistance to therapy.
Interventions
DRUGEnzalutamide
Sponsors
Astellas Pharma Inc
Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Pfizer
Study design
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed prostate cancer * Presence of metastatic disease to the bone * Ongoing androgen deprivation therapy
Exclusion criteria
* Severe concurrent disease * Metastases in the brain
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Bone Marrow Testosterone | 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. |
| Change From Baseline in Bone Marrow Dihydrotestosterone | 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. |
| Change From Baseline in Bone Marrow Testosterone at Week 9 by Prostate-Specific Antigen (PSA) Response Status | 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. |
| Change From Baseline in Bone Marrow Dihydrotestosterone at Week 9 by Prostate-Specific Antigen (PSA) Response Status | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Time to Study Drug Discontinuation | Duration of study treatment through the data cutoff, up to 3 years. | 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. |
| Change From Baseline in Urinary N-Telopeptide | Baseline, Week 5 | Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 5. |
| Percentage of Participants at Week 9 With a Response in Prostate-Specific Antigen (PSA) | Baseline, Week 9 | Serum samples for measurement of PSA levels were obtained at baseline prior to initiation of enzalutamide administration and at the Week 9 visit. |
Countries
United States
Participant flow
Recruitment details
Single center clinical trial
Participants by arm
| Arm | Count |
|---|---|
| Enzalutamide Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth. | 60 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Progressive Disease | 3 |
Baseline characteristics
| Characteristic | Enzalutamide |
|---|---|
| Age, Continuous | 67.9 years STANDARD_DEVIATION 9.99 |
| Age, Customized < 55 | 6 years |
| Age, Customized 55 to < 65 | 17 years |
| Age, Customized 65 to < 75 | 18 years |
| Age, Customized >= 75 | 19 years |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 59 / 60 |
| serious Total, serious adverse events | 13 / 60 |
Outcome results
Primary
Change From Baseline in Bone Marrow Dihydrotestosterone
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enzalutamide | Change From Baseline in Bone Marrow Dihydrotestosterone | 0.00 ng/mL | Standard Deviation 0.022 |
Primary
Change From Baseline in Bone Marrow Dihydrotestosterone at Week 9 by Prostate-Specific Antigen (PSA) Response Status
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enzalutamide | 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 |
| Enzalutamide, PSA Non-Responders at Week 9 | Change From Baseline in Bone Marrow Dihydrotestosterone at Week 9 by Prostate-Specific Antigen (PSA) Response Status | 0.00 ng/mL | Standard Deviation 0 |
p-value: 0.337t-test, 2 sided
Primary
Change From Baseline in Bone Marrow Testosterone
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enzalutamide | Change From Baseline in Bone Marrow Testosterone | 0.05 ng/mL | Standard Deviation 0.072 |
Primary
Change From Baseline in Bone Marrow Testosterone at Week 9 by Prostate-Specific Antigen (PSA) Response Status
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enzalutamide | 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 |
| Enzalutamide, PSA Non-Responders 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 0.034 |
p-value: 0.9427t-test, 2 sided
Secondary
Change From Baseline in Urinary N-Telopeptide
Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 65.
Time frame: Baseline, Week 65
Population: Participants who received any amount of enzalutamide and had urinary N-telopeptide measurements at baseline and at Week 65.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enzalutamide | Change From Baseline in Urinary N-Telopeptide | 17.67 mmol/mmol creatinine | Standard Deviation 17.131 |
Secondary
Change From Baseline in Urinary N-Telopeptide
Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 49.
Time frame: Baseline, Week 49
Population: Participants who received any amount of enzalutamide and had urinary N-telopeptide measurements at baseline and at Week 49.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enzalutamide | Change From Baseline in Urinary N-Telopeptide | -2.36 mmol/mmol creatinine | Standard Deviation 26.526 |
Secondary
Change From Baseline in Urinary N-Telopeptide
Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 57.
Time frame: Baseline, Week 57
Population: Participants who received any amount of enzalutamide and had urinary N-telopeptide measurements at baseline and at Week 57.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enzalutamide | Change From Baseline in Urinary N-Telopeptide | -9.33 mmol/mmol creatinine | Standard Deviation 37.824 |
Secondary
Change From Baseline in Urinary N-Telopeptide
Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 5.
Time frame: Baseline, Week 5
Population: Participants who received any amount of enzalutamide and had urinary N-telopeptide measurements at baseline and at Week 5.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enzalutamide | Change From Baseline in Urinary N-Telopeptide | 34.81 mmol/mmol creatinine | Standard Deviation 137.361 |
Secondary
Change From Baseline in Urinary N-Telopeptide
Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 9.
Time frame: Baseline, Week 9
Population: Participants who received any amount of enzalutamide and had urinary N-telopeptide measurements at baseline and at Week 9.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enzalutamide | Change From Baseline in Urinary N-Telopeptide | 205.84 mmol/mmol creatinine | Standard Deviation 1334.82 |
Secondary
Change From Baseline in Urinary N-Telopeptide
Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 17.
Time frame: Baseline, Week 17
Population: Participants who received any amount of enzalutamide and had urinary N-telopeptide measurements at baseline and at Week 17.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enzalutamide | Change From Baseline in Urinary N-Telopeptide | -0.92 mmol/mmol creatinine | Standard Deviation 205.941 |
Secondary
Change From Baseline in Urinary N-Telopeptide
Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 25.
Time frame: Baseline, Week 25
Population: Participants who received any amount of enzalutamide and had urinary N-telopeptide measurements at baseline and at Week 25.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enzalutamide | Change From Baseline in Urinary N-Telopeptide | -18.96 mmol/mmol creatinine | Standard Deviation 278.112 |
Secondary
Change From Baseline in Urinary N-Telopeptide
Time frame: Baseline, Week 33
Population: Participants who received any amount of enzalutamide and had urinary N-telopeptide measurements at baseline and at Week 33.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enzalutamide | Change From Baseline in Urinary N-Telopeptide | -89.36 mmol/mmol creatinine | Standard Deviation 363.14 |
Secondary
Change From Baseline in Urinary N-Telopeptide
Samples for measurement of urinary N-telopeptide were collected at baseline prior to initiation of enzalutamide administration and at Week 41.
Time frame: Baseline, Week 41
Population: Participants who received any amount of enzalutamide and had urinary N-telopeptide measurements at baseline and at Week 41.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enzalutamide | Change From Baseline in Urinary N-Telopeptide | -2.00 mmol/mmol creatinine | Standard Deviation 22.414 |
Secondary
Median Time to Study Drug Discontinuation
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enzalutamide | Median Time to Study Drug Discontinuation | 5.0 months |
Secondary
Percentage of Participants at Week 9 With a Response in Prostate-Specific Antigen (PSA)
Serum samples for measurement of PSA levels were obtained at baseline prior to initiation of enzalutamide administration and at the Week 9 visit.
Time frame: Baseline, Week 9
Population: Participants who received any amount of enzalutamide and had PSA values at baseline and at the Week 9 Visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Enzalutamide | 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 |
| Enzalutamide | 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 |