Enzalutamide & Dutasteride/Finasteride as 1st Line Treatment for Patients =/> 65 Years Old With Prostate Cancer.

Study Overview
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Brief Summary
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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
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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

Official Title
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A Phase II Study of Enzalutamide Plus Dutasteride/Finasteride as First Line Treatment for Vulnerable Patients ≥ 65 Years With Systemic Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Enzalutamide and Dutasteride or finasteride


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enzalutamide and dutasteride or finasteride<br>Use of either 1. Enzalutamide and dutasteride or 2. Enzalutamide and finasteride. | Drug: Enzalutamide and Dutasteride or finasteride<br>* Use of either two oral drugs together Enzalutamide by mouth daily and dutasteride by mouth daily or Enzalutamide by mouth daily and finasteride by mouth daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSA Progression Free Survival | Time (months) from initiation of study treatment to PSA progression, defined by Prostate Cancer Clinical Trials Working Group 2 criteria. | up to approximately 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in lowest PSA level compared to baseline PSA level (Absolute PSA response) | Change in lowest PSA level at follow up compared to baseline PSA level | up to approximately 36 months | 
| Time to PSA Nadir | Time (months) to achieve the lowest PSA value compared to baseline PSA level | up to approximately 36 months | 
| Number of participants who experience a treatment-related adverse events. | Adverse events will be defined according to CTCAE version 4.0. | up to approximately 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prostate