Abiraterone, Radiotherapy and Short-Term Androgen Deprivation in Unfavorable Localized Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Abiraterone acetate; Androgen deprivation; Radiation Therapy; Prednisone
Intervention description: 1000 mg orally once a day for 6 months.; LHRH analog (at discretion of treating physician) will be administered over 6 months (for example, leuprolide acetate 22.5mg IM or goserelin acetate 10.8mg SC given every 3 months for 2 doses).; Daily (Monday-Friday) for 8 weeks, final dose of 75-80 Gy; 5 mg tablet once daily for 6 months.
Intervention MeSH terms: Prednisone; Abiraterone Acetate; Androgens
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 37.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The addition of abiraterone acetate to standard treatment of radiotherapy and short-term
      androgen deprivation will increase the frequency of undetectable PSA.
    

Eligibility criteria:

        Inclusion Criteria:

          -  One of the following high risk criteria:

          -  Gleason Score 7 with PSA ≤ 20 ng/ml and clinical T1-2, or

          -  Gleason Score 8-10, PSA ≤ 20 ng/ml and clinical T1-2a, or

          -  PSA 10.1-40 ng/ml with GS < 7 and clinical T1-2, or

          -  Clinical T3 with Gleason Score < 7 and PSA ≤ 10 ng/ml.

          -  ECOG Performance Status ≤ 1

          -  Digital rectal exam within 90 days of registration on study

          -  CBC with differential with adequate bone marrow function defined as follows:

          -  Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3, Platelets > 100,000/µL and
             Hemoglobin ≥ 9g/dL

          -  Serum potassium ≥ 3.5 mEq/L

          -  Serum albumin > 3.0 g/dl

          -  Total bilirubin < 1.5 X of institutional upper limit of normal (ULN)

          -  AST(SGOT)/ALT(SGPT) < 1.5 X ULN

          -  Calculated creatinine clearance > 60 mL/min

          -  Age > 18 years

          -  Able to swallow a whole tablet and take abiraterone acetate on an empty stomach
             (defined as no food for two hours before and one hour after abiraterone acetate
             ingestion)

          -  Ability to understand and sign a written informed consent document

          -  Written authorization for use and release of health and research study information has
             been obtained

          -  Be willing/able to adhere to the prohibitions and restrictions specified in this
             protocol

          -  Subjects who have partners of childbearing potential must be willing to use a method
             of birth control with adequate barrier protections as determined acceptable by the
             principal investigator during the study and for 1 week after the last dose of
             abiraterone acetate.

        Exclusion Criteria:

          -  Bone, visceral or soft tissue metastasis, including lymph nodes (>2 cm in longest
             diameter)

          -  Prior therapy for prostate cancer [Exceptions: LHRH agonist or antagonist may have
             been initiated within 30 days prior to enrollment. Bicalutamide may have been given
             within 60 days of enrollment as long as it has been stopped at least 7 days before
             enrollment and total duration was no longer than 30 days. This is to allow enrollment
             of those who have been given bicalutamide as a bridge for LHRH agonist/antagonist. It
             is highly unlikely a short non-overlapping course of bicalutamide will interact with
             abiraterone acetate in a measurable way. Previous alpha-reductase inhibitor use
             allowed IF patient has not been taking for at least 30 days prior to abiraterone
             acetate initiation, OR if alpha reductase inhibitor was not used as a primary
             treatment of prostate cancer and the PSA on alpha-reductase inhibitor remains within
             eligibility when doubled. ]

          -  Known serum testosterone ≤ 150 ng/dl or symptoms of hypogonadism (fatigue, hot
             flashes, hair loss, loss of muscle mass, osteoporosis, low libido, depression) prior
             to ADT initiation not explained by other medical co-morbidity OR history of
             testosterone supplement. If questionable, serum testosterone level greater than 150
             ng/dl can be used to exclude hypogonadism.

          -  Previous malignancy within 3 years other than non-melanomatous skin cancer and
             non-muscle invasive bladder cancer

          -  Previous pelvic radiotherapy that would prevent prostate/SV irradiation

          -  Uncontrolled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95 mmHg). Patients
             with a history of hypertension are allowed provided blood pressure is controlled by
             anti-hypertensive therapy

          -  History of gastrointestinal disorders that may interfere with the absorption of study
             drug (including gastric bypass surgery)

          -  Concurrent spironolactone use

          -  Significant concurrent medical condition that would make prednisone/prednisolone use
             contraindicated or would interfere with the patient's ability to participate in the
             trial

          -  Receiving any investigational agents currently or within 30 days prior to study
             screening

          -  Prior demonstrated hypersensitivity, intolerance or allergy to abiraterone acetate,
             prednisone or their excipients

          -  Active co-morbidity, defined as follows:

               -  Chronic liver disease with cirrhosis (Child-Pugh B or C) or active hepatitis B or
                  C

               -  History of pituitary or adrenal dysfunction

               -  Poorly controlled diabetes mellitus (A1c >9% or history of complications
                  including peripheral neuropathy, end organ damage, hospitalization, amputation)

               -  Poorly controlled glaucoma

               -  Clinically significant heart disease as evidenced by myocardial infarction, or
                  arterial thrombotic events in the past 6 months, severe or unstable angina, or
                  New York Heart Association (NYHA) Class III-IV heart disease or known cardiac
                  ejection fraction measurement of < 50% at baseline.

               -  Clinical evidence of active infection of any type, including active or
                  symptomatic viral hepatitis.

               -  Known immune deficiency and/or HIV-positive patients

               -  Any medical condition that warrants long-term corticosteroid use in excess of
                  study dose

          -  Patients taking strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin,
             rifabutin, rifapentine, phenobarbital)

          -  Any condition that in the opinion of the Principal Investigator, would compromise the
             well-being of the subject or the study or prevent the subject from meeting or
             performing the study requirements