A Phase II Study of Increased-Dose Abiraterone Acetate in Patients With Castration Resistant Prostate Cancer
Condition: Castration Resistant Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Abiraterone Acetate; Prednisone
Intervention description: Standard dose participants:
1,000 mg, once daily, oral administration.
Dose escalation participants:
1,000 mg, twice daily, oral administration; 5 mg, twice daily, oral administration
Intervention MeSH terms: Prednisone; Abiraterone Acetate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: Simon's 2 stage minimax design for accrual.
Masking: None (Open Label)
Enrollment: 41.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: CRPC; Prostate; Cancer

Summary:

      The purpose of this study is to find out what effects, good and/or bad,an increased dose of
      Abiraterone Acetate in combination with prednisone has on patients and their prostate cancer.
      This study will investigate whether an increased-dose (2,000mg daily) is safe and potentially
      effective when given to patients whose cancer has grown while taking the standard dose.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have signed an informed consent document indicating that the subjects understands the
             purpose of and procedures required for the study and are willing to participate in the
             study

          -  Be willing/able to adhere to the prohibitions and restrictions specified in this
             protocol

          -  Written Authorization for Use and Release of Health and Research Study Information has
             been obtained

          -  Male aged 18 years and above

          -  Able to swallow the study drug whole as a tablet

          -  Willing to take abiraterone acetate on an empty stomach; no food should be consumed at
             least two hours before and for at least one hour after the dose of abiraterone acetate
             is taken

          -  Patients who have partners of childbearing potential must be willing to use a method
             of birth control with adequate barrier protection as determined to be acceptable by
             the principal investigator and sponsor during the study and for 1 week after last
             study drug administration.

          -  Have a baseline serum potassium of ≥ 3.5 milliequivalents per litre (mEq/L)

          -  Have aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin
             levels < 1.5 x upper limit of normal (ULN)

          -  Have a serum albumin of ≥ 3.0 g/dL

          -  Total bilirubin ≤ 1.5 x ULN (In patients with known Gilbert Syndrome, a total
             bilirubin ≤ 3.0 x ULN, with direct bilirubin ≤ 1.5 x ULN is acceptable)

          -  Have a platelet count of ≥ 100,000/μL

          -  Have an absolute neutrophil count of > 1500 cell/mm3

          -  Have a calculated creatinine clearance ≥ 60 mL/min

          -  Have a hemoglobin of ≥ 9.0 g/dL

          -  Have histologically confirmed adenocarcinoma of the prostate.

          -  No prior therapy with chemotherapy for metastatic prostate cancer.

          -  Have metastatic disease based on a positive bone scan or objective imaging on CT scan.

          -  Have ongoing gonadal androgen deprivation therapy with Luteinizing hormone-releasing
             hormone (LHRH) analogues or orchiectomy. Patients who have not had an orchiectomy must
             be maintained on effective LHRH analogue therapy for the duration of the trial.

          -  Testosterone < 50 ng/dL.

          -  Progressive disease after androgen deprivation: PSA evidence for progressive prostate
             cancer consists of a PSA level of at least 2 ng/ml which has risen on at least 2
             successive occasions, at least 2 weeks apart. If the confirmatory PSA value is less
             than the screening PSA value, then an additional test for rising PSA will be required
             to document progression.

          -  Antiandrogen Withdrawal (AAWD): Patients who are receiving an antiandrogen as part of
             primary androgen ablation must demonstrate disease progression following
             discontinuation of antiandrogen.

          -  Disease progression after antiandrogen withdrawal is defined as 2 consecutive rising
             PSA values, obtained at least 2 weeks apart, or documented osseous or soft tissue
             progression.

          -  For patients receiving flutamide, at least one of the PSA values must be obtained 4
             weeks or more after flutamide discontinuation.

          -  For patients receiving bicalutamide or nilutamide, at least one of the PSA values must
             be obtained 6 weeks or more after antiandrogen discontinuation.

          -  No antiandrogen withdrawal response is expected in patients in whom antiandrogen
             therapy did NOT result in a decline in PSA or in those patients in whom the response
             to antiandrogens was < 3 months. Therefore, it is not necessary to wait for AAWD in
             patients without PSA decline on an anti-androgen or in those in whom a PSA response
             lasted < 3 months.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1

          -  Life expectancy of ≥ 12 weeks.

        Exclusion Criteria:

          -  Active infection or other medical condition that would make prednisone/prednisolone
             (corticosteroid) use contraindicated

          -  Known brain metastasis

          -  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 treatment

          -  Active or symptomatic viral hepatitis or chronic liver disease

          -  History of pituitary or adrenal dysfunction

          -  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 II-IV heart disease or cardiac ejection fraction
             measurement of < 50 % at baseline

          -  Atrial Fibrillation, or other cardiac arrhythmia requiring medical therapy

          -  Administration of an investigational therapeutic within 30 days of screening

          -  Have poorly controlled diabetes

          -  Have a history of gastrointestinal disorders (medical disorders or extensive surgery)
             that may interfere with the absorption of the study agents

          -  Have a pre-existing condition that warrants long-term corticosteroid use in excess of
             study dose

          -  Have known allergies, hypersensitivity, or intolerance to abiraterone acetate or
             prednisone or their excipients

          -  Any condition which, in the opinion of the investigator, would preclude participation
             in this trial.

          -  Pure small cell carcinoma of the prostate or any mixed histology cancer of the
             prostate (eg: neuroendocrine) which contains < 50% adenocarcinoma.

          -  Therapy with other hormonal therapy, including any dose of megestrol acetate (Megace),
             finasteride (Proscar), dutasteride (Avodart) any herbal product known to decrease PSA
             levels (e.g., Saw Palmetto and PC-SPES), or any systemic corticosteroid within 4 weeks
             prior to first dose of study drug.

          -  Prior therapy with Abiraterone Acetate or other CYP17 inhibitor(s) including TAK-700
             or TOK-001, or investigational agent(s) targeting the androgen receptor for metastatic
             prostate cancer.

          -  Prior therapy with ketoconazole for > 2 weeks for prostate cancer.

          -  Therapy with supplements or complementary medicines/botanicals within 4 weeks of first
             dose of study drug, except for any combination of the following:

          -  Conventional multivitamin supplements

          -  Selenium

          -  Lycopene

          -  Soy supplements

          -  Prior radiation therapy completed < 4 weeks prior to enrollment

          -  Prior chemotherapy for castration resistant prostate cancer. Patients who have
             received chemotherapy for early stage prostate cancer (e.g. as part of a neoadjuvant
             or adjuvant trial) or for other malignancies are eligible provided that >1 year has
             passed since the administration of the last chemotherapy dose.

          -  Any "currently active" second malignancy, other than non-melanoma skin cancer.
             Patients are not considered to have a "currently active" malignancy, if they have
             completed therapy and are considered by their physician to be at least less than 30%
             risk of relapse over next year.

          -  Active psychiatric illnesses/social situations that would limit compliance with
             protocol requirements.

          -  Patients in whom urgent chemotherapy, in the opinion of the treating physician, is
             indicated should not be enrolled in this study.