Castration Resistant Prostate Cancer, Prostate Carcinoma Metastatic to the Bone
Conditions
Keywords
Cancer of the Prostate
Brief summary
The purpose of this study is to evaluate 18F-sodium fluoride positron-emission tomography / computed tomography (18F-NaF PET/CT) imaging as a method for determining treatment response in metastatic bone lesions in patients who are receiving enzalutamide for castration-resistant prostate cancer.
Interventions
DRUGEnzalutamide
Sponsors
Astellas Pharma Inc
Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, or signet cell or small cell features; * Presence of bone metastatic disease as assessed by at least two lesions on whole body metastable technetium-methylene diphosphonate (99mTc-MDP) bone scintigraphy; * Throughout the study, ongoing androgen deprivation therapy with a luteinizing hormone-releasing hormone (LHRH) analogue or prior bilateral orchiectomy (medical or surgical castration); * Testosterone ≤ 1.73 nmol/L (≤ 50 ng/dL) at screening; * Progressive disease on androgen deprivation therapy at screening defined as a minimum of two sequentially rising prostate-specific antigen (PSA) values (PSA1 \< PSA2 \< PSA3); * The screening PSA (PSA3) must be ≥ 2 μg/L (≥ 2 ng/mL).
Exclusion criteria
* Prior enzalutamide, abiraterone acetate, aminoglutethimide, ketoconazole, radium Ra 223 dichloride or other bone-targeting radionuclides, or cytotoxic chemotherapy in the CRPC setting for the treatment of prostate cancer or participation in a clinical trial of an investigational agent that inhibits the androgen receptor or androgen synthesis (unless treatment was placebo); * Treatment with hormonal therapy (eg, androgen receptor inhibitors, 5-alpha reductase inhibitors) or biologic therapy for prostate cancer (other than LHRH analogue therapy) within 4 weeks before enrollment; * Initiation of new treatment with denosumab, bisphosphonates, or systemic corticosteroids for treatment of prostate cancer within 4 weeks before enrollment; * Use of an investigational agent within 4 weeks before the screening visit; * Radiation therapy to bone within 4 weeks before enrollment; * Use of opiate analgesics for prostate cancer pain within 4 weeks before enrollment; * Screening 99mTc-MDP bone scintigraphy showing a superscan; * Visceral (eg, lung, liver) metastatic disease. Adenopathy is allowed; * Current or previously treated brain metastasis or active leptomeningeal disease; * History of seizure any time in the past for any reason or any condition that may predispose to seizures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With at Least (>=) 1 Responding Bone Lesion Assessed by Total Sodium Fluoride (NaF) Standardized Uptake Value [SUVtotal] at Third 18F-NaF PET/CT Imaging (NaF-3) Schedule | At NaF-3 schedule: at time of PSA, or radiographic(bone or soft tissue), or clinically relevant progression, or at 2years without progression after treatment initiation, whichever occurred first(From first dose of study drug up to maximum of 34.1 months) | Bone lesion responded: if its change from baseline in SUVtotal is below limit of agreement (LOA, no specific value, based upon test/retest analysis using software). SUVtotal: total NaF uptake,indicated tumor burden across all bone lesions/in individual lesions reflecting bone-metastatic prostate cancer.NaF-3 performed on any of these: 1) prostate-specific antigen (PSA) progression(increase of \>=25% and absolute increase of \>=2.0 ng/mL above nadir); 2) bone progressive disease(PD)(appearance of \>=2 new lesions after screening assessed by technetium Tc 99m medronate \[99mTc-MDP\] bone scintigraphy); 3) soft tissue PD; 4) clinically relevant progression by investigator; 5) at 2 years without progression after treatment initiation. PD, RECIST1.1:\>=20% increase in sum of diameters of target lesions,(reference smallest sum on study, included baseline sum if that is smallest on study),relative increase of 20%,sum of diameters indicated absolute increase of \>=5mm, appearance of \>=1 new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Heterogeneity of Response Across All Bone Lesions as Measured by Global Heterogeneity of NaF Standardized Uptake (SUVhetero) Score at Third 18F-NaF PET/CT Imaging (NaF-3) Schedule | At NaF-3 schedule: at time of PSA, or radiographic(bone or soft tissue), or clinically relevant progression, or at 2years without progression after treatment initiation, whichever occurred first(From first dose of study drug up to maximum of 34.1 months) | Global SUVhetero score:Sum of(SUVmean of each lesion minus global SUVmean of all lesion)\^2/number of lesions,measure of heterogeneity of tumor activity across all bone lesions.SUVmean(mean NaF uptake)indicated average activity of each lesions.Real limits for SUVhetero score ranged:0(minimum) to infinite(maximum).Higher global SUVhetero score:more heterogeneity in bone lesion activity.NaF-3 performed on any of these 1)PSA progression(increase of\>=25% and absolute increase of\>=2.0ng/mL above nadir);2)bone PD(appearance of\>=2 new lesions after screening assessed by 99mTc-MDP bone scintigraphy);3)soft tissue PD(RECIST1.1);4)clinically relevant progression by investigator;5)at 2years without progression after treatment initiation.PD perRECIST1.1:\>=20%increase in sum of diameters of target lesions,(reference smallest sum on study,this included baseline sum if that is smallest on study),relative increase of20%,sum of diameters indicated absolute increase of\>=5mm,appearance of\>=1 new lesions. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Enzalutamide 160 mg (18F-NaF PET/CT) Chemotherapy naive participants with progressive bone-metastatic CRPC were enrolled to receive enzalutamide 160 mg per day as 4 capsules (each capsule of 40 mg), orally, once daily. 18F-NaF PET/CT was evaluated to determine treatment response in metastatic bone lesions of enrolled participants in the study. Maximum treatment exposure was 34.1 months. | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 1 |
| Overall Study | Disease progression | 16 |
| Overall Study | Transitioned to study-NCT02960022 | 5 |
Baseline characteristics
| Characteristic | Enzalutamide 160 mg (18F-NaF PET/CT) |
|---|---|
| Age, Continuous | 72.0 years STANDARD_DEVIATION 10.07 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 21 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 23 |
| other Total, other adverse events | 22 / 23 |
| serious Total, serious adverse events | 9 / 23 |
Outcome results
Primary
Percentage of Participants With at Least (>=) 1 Responding Bone Lesion Assessed by Total Sodium Fluoride (NaF) Standardized Uptake Value [SUVtotal] at Third 18F-NaF PET/CT Imaging (NaF-3) Schedule
Bone lesion responded: if its change from baseline in SUVtotal is below limit of agreement (LOA, no specific value, based upon test/retest analysis using software). SUVtotal: total NaF uptake,indicated tumor burden across all bone lesions/in individual lesions reflecting bone-metastatic prostate cancer.NaF-3 performed on any of these: 1) prostate-specific antigen (PSA) progression(increase of \>=25% and absolute increase of \>=2.0 ng/mL above nadir); 2) bone progressive disease(PD)(appearance of \>=2 new lesions after screening assessed by technetium Tc 99m medronate \[99mTc-MDP\] bone scintigraphy); 3) soft tissue PD; 4) clinically relevant progression by investigator; 5) at 2 years without progression after treatment initiation. PD, RECIST1.1:\>=20% increase in sum of diameters of target lesions,(reference smallest sum on study, included baseline sum if that is smallest on study),relative increase of 20%,sum of diameters indicated absolute increase of \>=5mm, appearance of \>=1 new lesions.
Time frame: At NaF-3 schedule: at time of PSA, or radiographic(bone or soft tissue), or clinically relevant progression, or at 2years without progression after treatment initiation, whichever occurred first(From first dose of study drug up to maximum of 34.1 months)
Population: Analysis population included all enrolled participants who received any amount of study medication and who also have non-missing scans at both NaF-1 and NaF-3. Here, Overall Number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enzalutamide 160 mg (18F-NaF PET/CT) | Percentage of Participants With at Least (>=) 1 Responding Bone Lesion Assessed by Total Sodium Fluoride (NaF) Standardized Uptake Value [SUVtotal] at Third 18F-NaF PET/CT Imaging (NaF-3) Schedule | 100.0 percentage of participants |
Secondary
Mean Heterogeneity of Response Across All Bone Lesions as Measured by Global Heterogeneity of NaF Standardized Uptake (SUVhetero) Score at Third 18F-NaF PET/CT Imaging (NaF-3) Schedule
Global SUVhetero score:Sum of(SUVmean of each lesion minus global SUVmean of all lesion)\^2/number of lesions,measure of heterogeneity of tumor activity across all bone lesions.SUVmean(mean NaF uptake)indicated average activity of each lesions.Real limits for SUVhetero score ranged:0(minimum) to infinite(maximum).Higher global SUVhetero score:more heterogeneity in bone lesion activity.NaF-3 performed on any of these 1)PSA progression(increase of\>=25% and absolute increase of\>=2.0ng/mL above nadir);2)bone PD(appearance of\>=2 new lesions after screening assessed by 99mTc-MDP bone scintigraphy);3)soft tissue PD(RECIST1.1);4)clinically relevant progression by investigator;5)at 2years without progression after treatment initiation.PD perRECIST1.1:\>=20%increase in sum of diameters of target lesions,(reference smallest sum on study,this included baseline sum if that is smallest on study),relative increase of20%,sum of diameters indicated absolute increase of\>=5mm,appearance of\>=1 new lesions.
Time frame: At NaF-3 schedule: at time of PSA, or radiographic(bone or soft tissue), or clinically relevant progression, or at 2years without progression after treatment initiation, whichever occurred first(From first dose of study drug up to maximum of 34.1 months)
Population: Analysis population included all enrolled participants who received any amount of study medication and who also have non-missing scans at both NaF-1 and NaF-3. Here, Overall Number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enzalutamide 160 mg (18F-NaF PET/CT) | Mean Heterogeneity of Response Across All Bone Lesions as Measured by Global Heterogeneity of NaF Standardized Uptake (SUVhetero) Score at Third 18F-NaF PET/CT Imaging (NaF-3) Schedule | 3.9 unit on SUVhetero score | Standard Deviation 3.17 |