Trial of Radiotherapy With Leuprolide and Enzalutamide in High Risk Prostate Cancer
Condition: Prostatic Neoplasms; Pelvic Nodal
MeSH terms: Prostatic Neoplasms
Intervention: Enzalutamide; Leuprolide; Intensity-Modulated Radiation Therapy
Intervention description: Given orally; Given via intramuscular injection; A total dose of 45 Gy in 25 fractions of 1.8 Gy each.
Intervention MeSH terms: Leuprolide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the safety of giving enzalutamide with leuprolide acetate before
      and after radiation therapy and to see how well it works in treating patients with prostate
      cancer that is at high risk of returning. Radiation therapy uses high-energy x-rays to kill
      tumor cells and shrink tumors. Most types of prostate cancer also need testosterone to grow
      and spread. After radiation therapy, patients often receive treatments to reduce testosterone
      to prevent the cancer from returning. Leuprolide acetate works by reducing the amount of
      testosterone that the body makes. Enzalutamide is a stronger treatment that may block
      testosterone from reaching cancer cells. Adding enzalutamide to treatment with leuprolide
      acetate after radiation therapy may help prevent high-risk prostate cancer from returning and
      improve patient survival.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically confirmed diagnosis of adenocarcinoma of the prostate within 180 days
             prior to registration at very high risk of recurrence as determined by 2 or more of
             the following combinations:

               -  cT3a/b

               -  PSA ≥20

               -  Gleason score 8-10

               -  ≥33% core involvement OR any patient with pelvic lymph node involvement ≥1cm as
                  determined by pelvic CT or MRI imaging will meet eligibility criteria for
                  enrollment.

          2. Standard staging exams for patients with high-risk prostate cancer including bone scan
             or NaF Positron Emission Tomography (PET) /CT scan, and pelvic and prostate MRI.

          3. No distant metastases (M0) on bone scan or NaF PET/CT within 90 days prior to
             registration. Equivocal bone scan findings are allowed if the physician determines
             that distant metastases are unlikely based on clinical judgment.

          4. Zubrod Performance Status 0-2 within 60 days prior to enrollment.

          5. Age ≥18

          6. Complete blood count (CBC) with differential obtained within 30 days prior to
             registration on study, with adequate bone marrow function defined as follows:

               1. Absolute neutrophil count (ANC) ≥1,800 cells/mm3

               2. Platelets ≥100,000 cells/mm3

               3. Hemoglobin ≥8.0 g/dl (The use of transfusion or other intervention to achieve Hgb
                  ≥ 8.0 g/dl is acceptable)

               4. Serum creatinine <2.0 mg/dl and creatinine clearance >40 mL/min within 30 days
                  prior to registration

               5. Bilirubin <1.5 x ULN and Alanine aminotransferase (ALT) or Aspartate
                  aminotransferase (AST) <2 × ULN within 21 days prior to registration

          7. Patients, even if surgically sterilized (i.e., status post vasectomy), who:

               1. Agree to practice effective barrier contraception during the entire study
                  treatment period and for 4 months (120 days) after the last dose of study drug,
                  or

               2. Agree to completely abstain from intercourse

          8. Patient must be able to provide study-specific informed consent prior to study entry.

        Exclusion Criteria:

          1. Definite evidence of metastatic disease

          2. Prior radical prostatectomy or bilateral orchiectomy for any reason

          3. Prior invasive malignancy (except non-melanoma skin cancer) unless disease-free or not
             requiring systemic therapy for a minimum of 3 years.

          4. Prior systemic chemotherapy for prostate cancer (Note that prior chemotherapy for a
             different cancer is allowed).

          5. Prior radiotherapy, including brachytherapy, to the region of the prostate that would
             result in overlap of radiation therapy fields.

          6. Previous hormonal therapy such as LHRH agonists (e.g. goserelin, leuprolide),
             anti-androgens (e.g. flutamide, bicalutamide), estrogens (e.g. DES), or surgical
             castration (orchiectomy)

          7. Known hypersensitivity to enzalutamide or related compounds

          8. History of adrenal insufficiency

          9. Patients who are sexually active and not willing/able to use medically acceptable
             forms of contraception; this exclusion is necessary because the treatment involved in
             this study may be significantly teratogenic.

         10. Prior allergic reaction to the drugs involved in this protocol.

         11. Cushing's syndrome

         12. Severe chronic renal disease (serum creatinine >2.0 mg/dl and confirmed by creatinine
             clearance <40 mL/minute)

         13. Chronic liver disease (bilirubin >1.5x ULN, ALT or AST >2x ULN)

         14. Active/Uncontrolled Viral Hepatitis

         15. Chronic treatment with glucocorticoids within one year.

         16. History of seizure including febrile seizure or any condition that may predispose to
             seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss
             of consciousness requiring hospitalization). Also, current or prior treatment with
             antiepileptic medications for the treatment of seizures or history of loss of
             consciousness or transient ischemic attack within 12 months prior to randomization.

         17. Clinically significant cardiovascular disease including:

               1. Myocardial infarction within 6 months prior to screening

               2. Uncontrolled angina within 3 months prior to screening

               3. Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or
                  subjects with history of congestive heart failure NYHA class 3 or 4 in the past,
                  unless a screening echocardiogram or multigated acquisition (MUGA) scan performed
                  within 3 months results in a left ventricular ejection fraction that is ≥45%;

               4. History of clinically significant ventricular arrhythmias (e.g. ventricular
                  tachycardia, ventricular fibrillation, torsades de pointes);

               5. History of Mobitz II second degree or third degree heart block without a
                  permanent pacemaker in place;

               6. Uncontrolled hypertension as indicated by a resting systolic blood pressure >170
                  mm Hg or diastolic blood pressure >105 mm Hg at screening. Patients with
                  initially elevated systolic blood pressure >170 mm Hg or diastolic blood pressure
                  >105 mm Hg are eligible if they undergo medical management and are re-screened.