Prostate Cancer
Conditions
Keywords
prostate cancer, enzalutamide, radiation, hormone therapy
Brief summary
The study is being done to find out whether combining two FDA approved drugs along with radiation therapy for the treatment of high risk localized prostate cancer is safe and well tolerated.
Detailed description
* this pilot study will assess the safety and tolerability of combining enzalutamide with an gonadotropin-releasing hormone agonist (GnRH) and external beam radiation * Correlative imaging and tissue biopsy analysis will be performed to assess the radiographic response to enzalutamide plus gonadotropin-releasing hormone agonist (GnRH) therapy as well as intratumoral androgen signaling
Interventions
DRUGEnzalutamide
160mg by mouth each day
DRUGLeuprolide acetate
22.5 mg intramuscular every 3 months or 45mg intramuscular every 6 months
RADIATIONradiation
External beam radiation will be delivered as per standard radiation therapy protocol
Sponsors
Astellas Pharma US, Inc.
University of Texas Southwestern Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* histologically proven adenocarcinoma of the prostate within 6 months of screening * Eastern Cooperative Oncology Group(ECOG) score 0-2 * adequate organ and and blood marrow function * must be a candidate for long-term androgen deprivation in combination with external beam radiation for the treatment of high risk prostate cancer * patient must permit a targeted prostate biopsy at the time of study initiation or at the beginning of radiation treatment * men who are sexually active with female partners of child-bearing potential mush agree to use adequate contraception
Exclusion criteria
* prior treatment with agents known to have endocrine effects on prostate cancer * treatment with corticosteroids within 4 weeks of enrollment * treatment with androgens within 6 months of enrollment * may not be receiving any other investigational agents * Prostate specific antigen greater than 160ng/dL * history of malignancy( other than non-melanoma skin cancer) within 5 years * uncontrolled intercurrent illness * cardiovascular event within 6 months of enrollment * seizure or seizure disorder history * contraindications to MRI- pacemakers, clips, etc
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety, as Measured by the Number of Patients With at Least One Adverse Event as Assess by NCI Common Terminology Criteria for Adverse Events (CTCAE) vs. 40 When Combining Enzalutamide With a GnRH and External Beam Radiation | 12 months following initiation of treatment with enzalutamide plus GnRH agonist | Assessment will number of participants who experience adverse events greater than or equal to Grade 3, as defined by NCI Common terminology criteria for adverse events(CTCAE) v4.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fold Change in Intra-tumoral Androgen Regulated Gene Expression Pre and Post Combination Therapy | 12 months | Fold change of Intra-tumoral Androgen Regulated Gene Expression (PSA, FKBP5, TMPRSS2, and NDRG1) will be measure at 12 months post therapy. |
Countries
United States
Participant flow
Pre-assignment details
7 met criteria and were enrolled in the trial
Participants by arm
| Arm | Count |
|---|---|
| Enzalutamide, Leuprolide, Radiation Single arm Enzalutamide 160 mg daily for 6 months Leuprolide acetate 22.5mg every 3 months or 45mg every 6 months Radiation therapy as standard of care
Enzalutamide: 160mg by mouth each day
Leuprolide acetate: 22.5 mg intramuscular every 3 months or 45mg intramuscular every 6 months
radiation: External beam radiation will be delivered as per standard radiation therapy protocol | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | Enzalutamide, Leuprolide, Radiation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 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 | 4 Participants |
| Region of Enrollment United States | 7 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 7 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
Safety, as Measured by the Number of Patients With at Least One Adverse Event as Assess by NCI Common Terminology Criteria for Adverse Events (CTCAE) vs. 40 When Combining Enzalutamide With a GnRH and External Beam Radiation
Assessment will number of participants who experience adverse events greater than or equal to Grade 3, as defined by NCI Common terminology criteria for adverse events(CTCAE) v4.0
Time frame: 12 months following initiation of treatment with enzalutamide plus GnRH agonist
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Enzalutamide, Leuprolide, Radiation | Safety, as Measured by the Number of Patients With at Least One Adverse Event as Assess by NCI Common Terminology Criteria for Adverse Events (CTCAE) vs. 40 When Combining Enzalutamide With a GnRH and External Beam Radiation | 0 Participants |
Secondary
Fold Change in Intra-tumoral Androgen Regulated Gene Expression Pre and Post Combination Therapy
Fold change of Intra-tumoral Androgen Regulated Gene Expression (PSA, FKBP5, TMPRSS2, and NDRG1) will be measure at 12 months post therapy.
Time frame: 12 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Enzalutamide, Leuprolide, Radiation | Fold Change in Intra-tumoral Androgen Regulated Gene Expression Pre and Post Combination Therapy | Fold change in PSA | 0.54 Fold change |
| Enzalutamide, Leuprolide, Radiation | Fold Change in Intra-tumoral Androgen Regulated Gene Expression Pre and Post Combination Therapy | Fold change in FKBP5 | 2.2 Fold change |
| Enzalutamide, Leuprolide, Radiation | Fold Change in Intra-tumoral Androgen Regulated Gene Expression Pre and Post Combination Therapy | Fold change in TMPRSS2 | 0.65 Fold change |
| Enzalutamide, Leuprolide, Radiation | Fold Change in Intra-tumoral Androgen Regulated Gene Expression Pre and Post Combination Therapy | Fold change in NDRG1 | 0.36 Fold change |