Prostate Cancer
Conditions
Keywords
prostate
Brief summary
Determine the effect of enzalutamide and dutasteride or finasteride on the time to prostatic-specific antigen level increase in patients age 65 or older.
Detailed description
The primary objective of this study is to determine the effect of enzalutamide and dutasteride or finasteride on the time to prostatic-specific antigen progression in patients aged 65 or older receiving this combination as first line treatment for systemic prostate cancer. To determine the safety and toxicities of the study drug combination. To determine the time to prostatic-specific antigen nadir from the start of study treatment and to evaluate the absolute prostatic-specific antigen nadir as a result of the study drug combination
Interventions
DRUGEnzalutamide and Dutasteride or finasteride
Use of either two oral drugs together 1. Enzalutamide by mouth daily and dutasteride by mouth daily or 2. Enzalutamide by mouth daily and finasteride by mouth daily
Sponsors
University of Rochester
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
65 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features. Patients with systemic prostate cancer as defined by either a) hormonal naïve metastatic prostate cancer with radiographic evidence of visceral or osseous metastasis or b) biochemical recurrence prostate cancer that fulfills all of the following criteria: A minimum of three rising prostatic-specific antigen levels with an interval of =/\> 1 week between each test, The prostatic-specific antigen (PSA) value at the screening visit should be =/\> 2 ng/ml prostatic-specific antigen doubling time ≤ 9 months. Patients should be 65 years or older. Patients who are deemed not fit by comprehensive geriatric assessment or at high risk for side effects as determined by the treating physician. A case report form will be used to document the specifics of why each eligible patient is not considered an ideal candidate. Serum testosterone level \> 1.7 nmol/L (50 ng/dL) at the screening visit (non- castrate). Patients could have received hormonal therapy as part of definitive treatment for previous localized prostate cancer. However, they should be off any hormonal therapy for greater than six months prior to entry to clinical trial. Eastern Cooperative Oncology Group performance status of 0 to 2. Able to swallow the study drug and comply with study requirements.
Exclusion criteria
Severe concurrent disease or infection that, in the judgment of the investigator, would make the patient inappropriate for enrollment. Known brain metastases. Brain imaging studies are not required for eligibility if the patient has no neurologic signs or symptoms suggestive of brain metastasis. However, if brain imaging studies are performed, they must be negative for disease. Patient is receiving treatment for another active malignancy excluding localized cutaneous squamous or basal cell carcinoma. Prior treatment for systemic prostate cancer. Prior treatment with enzalutamide. Treatment with androgen receptor antagonists (bicalutamide, flutamide, nilutamide,), ketoconazole, abiraterone, finasteride, dutasteride, estrogens, or chemotherapy in an adjuvant setting within 6 months of enrollment (Day 1 visit) or plans to initiate treatment with any of these treatments. Treatment with therapeutic immunizations for prostate cancer (e.g., PROVENGE®) or plans to initiate treatment with any of these treatments during the study period. Use of herbal products that may decrease prostatic-specific antigen levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of prednisone/prednisolone per day within 4 weeks of enrollment (Day 1 visit) or plans to initiate treatment with any of these treatments during the study. Radiation therapy within 3 weeks (if single fraction of radiotherapy within 2 weeks) and radioisotope therapy within 8 weeks of enrollment (Day 1 visit). Participation in a previous clinical trial of an investigational agent that blocks androgen synthesis within six months. Participation in a previous clinical trial of enzalutamide. Use of an investigational agent within 4 weeks of enrollment (Day 1 visit) or plans to initiate treatment with an investigational agent during the study. Have used or plan to use from 30 days prior to enrollment (Day 1 visit) through the end of the study the following medications known to lower the seizure threshold or increase or decrease the bioavailability of the drug. Concomitant use of strong or moderately strong Cytochrome P450 isozyme inducers: Strong Cytochrome P450 isoenzyme 2C8 inhibitors like gemfibrozil, Strong Cytochrome P450 isoenzyme 2C8 inducers like Rifampin, Strong Cytochrome P450 isoenzyme 3A4 inhibitors like Itraconazole, Aminophylline/theophylline, Atypical antipsychotics (e.g., clozapine, olanzapine, risperidone, ziprasidone), Bupropion, Class IA and Class III antiarrhythmics (e.g., amiodarone, bretylium, disopyramide, ibutilide, procainamide, quinidine, sotalol); Dolasetron, Droperidol, Lithium, Macrolide antibiotics (e.g., erythromycin, clarithromycin); Pethidine, Phenothiazine antipsychotics (e.g., chlorpromazine, mesoridazine, thioridazine); Pimozide, Tricyclic and tetracyclic antidepressants(e.g., amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine). History of seizure, including any febrile seizure, loss of consciousness, or transient ischemia attack within 12 months of enrollment (Day 1 visit), or any condition that may predispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization). Clinically significant cardiovascular disease including: Myocardial infarction within 6 months, Uncontrolled angina within 3 months, Congestive heart failure New York Heart Association class 3 or 4, or patients with history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multigated acquisition scan performed within 3 months results in a left ventricular ejection fraction that is =/\> 45%, hypotension (systolic blood pressure \< 86 millimeters of mercury \[mmHg\] or bradycardia with a heart rate \< 50 beats per minute, uncontrolled hypertension as indicated by a resting systolic blood pressure of 170 mmHg or diastolic blood pressure \> 105 mmHg at the Screening or Study Day 1 visit. Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer within last 3 months). Major surgery within 4 weeks prior to enrollment (Day 1 visit). Absolute neutrophil count \< 1,500/µL, platelet count \< 100,000/µL, and hemoglobin \< 5.6 mmol/L (9 g/dL) at the Screening visit; (NOTE: patients may not have received any growth factors or blood transfusions within 7 days of the hematologic laboratory values obtained at the Screening visit).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prostate Specific Antigen (PSA) Progression Free Survival | 3 years. | Percentage of participants with progression-free survival at 3 years. PSA disease progression is defined as an increase in the PSA that is \>=25% and \>=2 ng/ml above the nadir PSA value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute PSA Response | up to approximately 8 years | Lowest PSA value achieved. |
| Time to PSA Nadir | up to approximately 8 years | Time (months) to achieve the lowest PSA value compared to baseline PSA level |
| Number of Participants Who Experience a Treatment-related Adverse Events. | up to approximately 8 years | Adverse events will be defined according to CTCAE version 4.0. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mean Quality of Life | baseline to week 61 | Change in quality of life score at follow up compared to baseline score, using FACT-P survey. The FACT-P survey is a 39 item questionnaire with a score that ranges from 0-156 with higher scores indicating better quality of life. |
| Comprehensive Geriatric Assessment Domains | Week 1 to approximately 36 months | Change in comprehensive geriatric assessment domains at follow up compared to baseline evaluation. |
| Number of Participants With a Change in Bone Density | baseline to week 103 | Change in bone density at week 103 compared to baseline bone density, measured using DEXA study. |
Countries
United States
Participant flow
Pre-assignment details
This is a single arm study that evaluates the effect of enzalutamide and a 5-alpha reductase inhibitor, with either dutasteride or finasteride. The sample size and power calculations were based on considering subjects using enzalutamide and a 5-alpha reductase inhibitor with either dutasteride or finasteride as a single treatment group. As a result, all analyses for study outcome were performed by including subjects using enzalutamide and a 5-alpha reductase inhibitor as one treatment group.
Participants by arm
| Arm | Count |
|---|---|
| Enzalutamide and Dutasteride or Finasteride Use of either 1. Enzalutamide and dutasteride or 2. Enzalutamide and finasteride.
Enzalutamide and Dutasteride or finasteride: Use of either two oral drugs together
1. Enzalutamide by mouth daily and dutasteride by mouth daily or
2. Enzalutamide by mouth daily and finasteride by mouth daily | 43 |
| Total | 43 |
Baseline characteristics
| Characteristic | Enzalutamide and Dutasteride or Finasteride |
|---|---|
| Age, Continuous | 78 years |
| 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 | 41 Participants |
| Region of Enrollment United States | 43 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 43 |
| other Total, other adverse events | 43 / 43 |
| serious Total, serious adverse events | 26 / 43 |
Outcome results
Primary
Prostate Specific Antigen (PSA) Progression Free Survival
Percentage of participants with progression-free survival at 3 years. PSA disease progression is defined as an increase in the PSA that is \>=25% and \>=2 ng/ml above the nadir PSA value.
Time frame: 3 years.
Population: This is a single arm study that evaluates the effect of enzalutamide and a 5-alpha reductase inhibitor, with either dutasteride or finasteride. The sample size and power calculations were based on considering subjects using enzalutamide and a 5-alpha reductase inhibitor with either dutasteride or finasteride as a single treatment group. As a result, primary study outcome analyses were performed by including subjects using enzalutamide and a 5-alpha reductase inhibitor as one treatment group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enzalutamide and Dutasteride or Finasteride | Prostate Specific Antigen (PSA) Progression Free Survival | 85.3 percentage of participants |
Secondary
Absolute PSA Response
Lowest PSA value achieved.
Time frame: up to approximately 8 years
Population: This is a single arm study that evaluates the effect of enzalutamide and a 5-alpha reductase inhibitor, with either dutasteride or finasteride. The sample size and power calculations were based on including subjects using enzalutamide and a 5-alpha reductase inhibitor with either dutasteride or finasteride as one treatment group. The analyses for this outcome included subjects using enzalutamide and a 5-alpha reductase inhibitor as one treatment group. One patient has missing data at 8 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enzalutamide and Dutasteride or Finasteride | Absolute PSA Response | 0.02 ng/dl |
Secondary
Number of Participants Who Experience a Treatment-related Adverse Events.
Adverse events will be defined according to CTCAE version 4.0.
Time frame: up to approximately 8 years
Population: This is a single arm study that evaluates the effect of enzalutamide and a 5-alpha reductase inhibitor, with either dutasteride or finasteride. The sample size and power calculations were based on including subjects using enzalutamide and a 5-alpha reductase inhibitor with either dutasteride or finasteride as one treatment group. The analyses for this outcome included subjects using enzalutamide and a 5-alpha reductase inhibitor as one treatment group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Enzalutamide and Dutasteride or Finasteride | Number of Participants Who Experience a Treatment-related Adverse Events. | 43 Participants |
Secondary
Time to PSA Nadir
Time (months) to achieve the lowest PSA value compared to baseline PSA level
Time frame: up to approximately 8 years
Population: This is a single arm study that evaluates the effect of enzalutamide and a 5-alpha reductase inhibitor, with either dutasteride or finasteride. The sample size and power calculations were based on including subjects using enzalutamide and a 5-alpha reductase inhibitor with either dutasteride or finasteride as one treatment group. The analyses for this outcome included subjects using enzalutamide and a 5-alpha reductase inhibitor as one treatment group. One subject has missing data at 8 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enzalutamide and Dutasteride or Finasteride | Time to PSA Nadir | 8.05 months |
Other Pre-specified
Comprehensive Geriatric Assessment Domains
Change in comprehensive geriatric assessment domains at follow up compared to baseline evaluation.
Time frame: Week 1 to approximately 36 months
Other Pre-specified
Mean Quality of Life
Change in quality of life score at follow up compared to baseline score, using FACT-P survey. The FACT-P survey is a 39 item questionnaire with a score that ranges from 0-156 with higher scores indicating better quality of life.
Time frame: baseline to week 61
Other Pre-specified
Number of Participants With a Change in Bone Density
Change in bone density at week 103 compared to baseline bone density, measured using DEXA study.
Time frame: baseline to week 103