Prostate Cancer
Conditions
Keywords
Prostate cancer, enzalutamide, ADT, radiation
Brief summary
The purpose of this study is to describe the 2 year progression-free survival in men with recurrent PSA-only disease after prostatectomy receiving combined enzalutamide and standard androgen-deprivation therapy (ADT) with salvage radiation therapy. Eligible men will have recurrent PSA-only prostate cancer within 4 years of prostatectomy, and a PSA of 0.2 - 4 in the absence of metastatic disease on CT and bone scans. In addition to standard ADT and radiation therapy, research participants will take enzalutamide once daily for six months. It is primarily hypothesized the 2 year PFS rate will be improved with the combined therapy compared to the historical control data in a similar patients setting.
Interventions
DRUGenzalutamide
160 mg orally once daily for six months
Two injections each lasting three months, for a total of six months of androgen deprivation therapy. Doctor will help determine which androgen deprivation drug to use.
RADIATIONRadiation Therapy
Daily (Monday-Friday) for 6-8 weeks, final dose of approximately 66 Gy
Sponsors
Medivation, Inc.
Astellas Pharma Inc
Duke University
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 confirmed diagnosis of prostate adenocarcinoma. Variants of prostate cancer, including neuroendocrine features and small cell carcinoma of the prostate, are not permitted. * Gleason sum of 7, 8, 9, or 10 at the time of prostatectomy. * PSA relapse within 4 years of prostatectomy defined by persistently detectable or rising PSA after surgery. * Evidence of disease recurrence or progression as evidenced by a PSA \> 0.20. This requires 2 consecutive rises in PSA, at least 1 week apart, over the post-prostatectomy nadir or one PSA value above 0.20 ng/mL if the patient failed to achieve a post-prostatectomy nadir of \< 0.2 ng/mL. * Age ≥ 18 years * Karnofsky performance status ≥ 70 * Adequate laboratory parameters * Adequate bone marrow function: ANC ≥1.5 x 109/L, Platelets ≥100 x 109/L, Hb \>9g/dL * AST/SGOT and ALT/SGPT ≤ 2.5 x Institutional Upper Limit of Normal (ULN) * Serum bilirubin ≤ 1.5 x Institutional ULN * Serum creatinine ≤ 1.5 x Institutional ULN or 24-hour clearance ≥ 50 mL/min * A minimum of 4 weeks from any major surgery prior to registration. * Ability to swallow, retain, and absorb oral medication. * Ability to understand and the willingness to sign a written informed consent document. * Must use a condom if having sex with a pregnant woman. * Male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 3 months after final study drug administration.
Exclusion criteria
* Radiographic evidence of metastatic disease. Patients with node-positive disease (\<2 positive nodes) at the time of radical prostatectomy are eligible. Patients with pelvic nodes up to 2 cm by short axis at the time of screening are eligible. Patients with any enlarged lymph nodes in the retroperitoneum or above the aortic bifurcation or with pelvic nodes ≥ 2 cm must be excluded. * PSA \> 4.0 ng/mL. * Testosterone level ≤ 100 ng/dL. * More than 1 month of prior hormone exposure or hormone exposure within 30 days of registration. Prior enzalutamide, ketoconazole, abiraterone, or TAK700 prohibited. Prior 5α reductase inhibitors are allowed. * Prior immunotherapy including sipuleucel-T. * Prior systemic chemotherapy (docetaxel, cabazitaxel, estramustine, other cytotoxic agents) * History of solid organ or stem cell transplantation. * History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, prior head or traumatic brain injury with loss of consciousness, prior or current space-occupying lesion in the brain). Also, history of loss of consciousness or transient ischemic attack within 12 months of Day 1 visit. * Known or suspected brain metastasis or active leptomeningeal disease. * Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol. * Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of enzalutamide or increase the risk of radiation (e.g., uncontrolled nausea, vomiting, diarrhea, malabsorption syndromes, prior small bowel resection, or inflammatory bowel disease). * Patients who have received prior prostate or pelvic radiotherapy, including external beam or brachytherapy. * Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy prior to registration. * Patients unable or unwilling to abide by the study protocol or cooperate fully with the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Two Year Progression-free Survival | 2 years | Percentage of patients surviving 2 years from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of first documented progression or death due to any cause. Progression-free was defined as being without one of the following: serum PSA value of 0.2 ng/mL or more above post-radiotherapy PSA nadir that continues to increase 4 weeks later OR if no nadir is experienced, two rising PSA values over 4 or more weeks OR evidence of clinical progression or initiation of systemic therapy for progressive disease |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Three Year Progression-free Survival | 3 years | Percentage of patients surviving 3 years from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of first documented progression or death due to any cause. Progression-free was defined as being without one of the following: serum PSA value of 0.2 ng/mL or more above post-radiotherapy PSA nadir that continues to increase 4 weeks later OR if no nadir is experienced, two rising PSA values over 4 or more weeks OR evidence of clinical progression or initiation of systemic therapy for progressive disease |
| Biochemical Progression-free Survival | 3 years | Percentage of patients surviving 2 and 3 years from the start of study treatment without progression of disease. Biochemical PFS was defined as the time from the date of study treatment initiation to the date of first documented progression or death due to any cause. Progression-free was defined as being without one of the following: serum PSA value of 0.2 ng/mL or more above post-radiotherapy PSA nadir that continues to increase 4 weeks later OR if no nadir is experienced, two rising PSA values over 4 or more weeks |
| PSA Less Than 0.1 | every year, up to 3 years | The percentage of men with PSA less than 0.1 ng/mL and testosterone greater than 100 |
| Time to Testosterone Recovery | 3 years | Percentage of patients with recovering testosterone to \> 100 at 1, 2, and 3 years. |
| Number of Patients With Adverse Events Related to Combination Enzalutamide, ADT, and XRT | 3 years | Safety and tolerability will be assessed using CTCAE v4.0 |
| PSA Nadir | 8 weeks | Median PSA nadir post-radiation therapy |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Enzalutamide Enzalutamide, Androgen Deprivation, and Radiation Therapy
enzalutamide: 160 mg orally once daily for six months
Androgen Deprivation: Two injections each lasting three months, for a total of six months of androgen deprivation therapy. Doctor will help determine which androgen deprivation drug to use.
Radiation Therapy: Daily (Monday-Friday) for 6-8 weeks, final dose of approximately 66 Gy | 38 |
| Total | 38 |
Baseline characteristics
| Characteristic | Enzalutamide |
|---|---|
| Age, Continuous | 64 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 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 | 34 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 38 |
| other Total, other adverse events | 38 / 38 |
| serious Total, serious adverse events | 2 / 38 |
Outcome results
Primary
Two Year Progression-free Survival
Percentage of patients surviving 2 years from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of first documented progression or death due to any cause. Progression-free was defined as being without one of the following: serum PSA value of 0.2 ng/mL or more above post-radiotherapy PSA nadir that continues to increase 4 weeks later OR if no nadir is experienced, two rising PSA values over 4 or more weeks OR evidence of clinical progression or initiation of systemic therapy for progressive disease
Time frame: 2 years
Population: One patient did not receive radiotherapy due to continual scar tissue development surrounding the ureters. This patient is not considered for analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enzalutamide | Two Year Progression-free Survival | 64.9 percentage |
Secondary
Biochemical Progression-free Survival
Percentage of patients surviving 2 and 3 years from the start of study treatment without progression of disease. Biochemical PFS was defined as the time from the date of study treatment initiation to the date of first documented progression or death due to any cause. Progression-free was defined as being without one of the following: serum PSA value of 0.2 ng/mL or more above post-radiotherapy PSA nadir that continues to increase 4 weeks later OR if no nadir is experienced, two rising PSA values over 4 or more weeks
Time frame: 3 years
Population: One patient did not receive radiotherapy due to continual scar tissue development surrounding the ureters. This patient is not considered for analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Enzalutamide | Biochemical Progression-free Survival | 2 year bPFS | 64.9 percentage |
| Enzalutamide | Biochemical Progression-free Survival | 3 year bPFS | 53.2 percentage |
Secondary
Number of Patients With Adverse Events Related to Combination Enzalutamide, ADT, and XRT
Safety and tolerability will be assessed using CTCAE v4.0
Time frame: 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enzalutamide | Number of Patients With Adverse Events Related to Combination Enzalutamide, ADT, and XRT | 36 participants |
Secondary
PSA Less Than 0.1
The percentage of men with PSA less than 0.1 ng/mL and testosterone greater than 100
Time frame: every year, up to 3 years
Population: One patient did not receive radiotherapy due to continual scar tissue development surrounding the ureters. This patient is not considered for analyses. Note that 11 patients did not have PSA measurements at 2 years and 24 did not have PSA measurements at 3 years. They are still included in the denominator.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Enzalutamide | PSA Less Than 0.1 | 2 year | 48.6 percentage |
| Enzalutamide | PSA Less Than 0.1 | 3 year | 32.4 percentage |
| Enzalutamide | PSA Less Than 0.1 | 1 year | 75.7 percentage |
Secondary
PSA Nadir
Median PSA nadir post-radiation therapy
Time frame: 8 weeks
Population: One patient did not receive radiotherapy due to continual scar tissue development surrounding the ureters. This patient is not considered for analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enzalutamide | PSA Nadir | 0 ng/ml |
Secondary
Three Year Progression-free Survival
Percentage of patients surviving 3 years from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of first documented progression or death due to any cause. Progression-free was defined as being without one of the following: serum PSA value of 0.2 ng/mL or more above post-radiotherapy PSA nadir that continues to increase 4 weeks later OR if no nadir is experienced, two rising PSA values over 4 or more weeks OR evidence of clinical progression or initiation of systemic therapy for progressive disease
Time frame: 3 years
Population: One patient did not receive radiotherapy due to continual scar tissue development surrounding the ureters. This patient is not considered for analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enzalutamide | Three Year Progression-free Survival | 53.2 percentage |
Secondary
Time to Testosterone Recovery
Percentage of patients with recovering testosterone to \> 100 at 1, 2, and 3 years.
Time frame: 3 years
Population: One patient did not receive radiotherapy due to continual scar tissue development surrounding the ureters. This patient is not considered for analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Enzalutamide | Time to Testosterone Recovery | 1 year | 94.6 percentage |
| Enzalutamide | Time to Testosterone Recovery | 2 year | 100 percentage |
| Enzalutamide | Time to Testosterone Recovery | 3 year | 100 percentage |