Phase I/II Study of Abiraterone Acetate and Prednisone in Combination With Cabazitaxel in Patients With Metastatic Castrate Resistant Prostate Cancer That is Refractory to Docetaxel
- Written informed consent has been obtained.
- Adults over 18 years of age.
- Histologically or cytologically proven adenocarcinoma of the prostate.
- Stage IV disease as evidenced by soft tissue, visceral and/or bony metastasis must be
Response Evaluation Criteria in Solid Tumors (RECIST) evaluable on CT scan and/or
- Progressive disease while receiving hormonal therapy or after surgical castration
documented by at least one of the following: (1) Increase in measurable disease per
RECIST 1.1. (2) Appearance of new lesions on bone scan consistent with progressive
prostate cancer (>2 new lesions on bone scans if this is the only measure of PD) (3)
rising PSA defined as 2 sequential increases above a previous lowest reference value.
Each value must be obtained at least 1 week apart.
- PSA at least 2 ng/mL
- Received prior docetaxel chemotherapy
- Received prior abiraterone, but not within the 3 months prior to study drug dosing.
Prior therapy with abiraterone is not required for enrollment in the phase I study.
- Testosterone level <50 ng/mL. Patients receiving Leutinizing hormone releasing
hormone (LHRH) agonists must be continued to maintain castrate levels of testosterone
while on study.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- Adequate hematologic function (platelet >100, 000/uL; neutrophil count of >1500
cell/mm3; hemoglobin >9.0 g/dL)
- Adequate renal function (Creatinine clearance >60 mL/min)
- Adequate potassium level > 3.5 mEq/dL
- Adequate hepatic function (bilirubin < 1.5 X upper limit of normal (ULN), alanine
aminotransferase (ALT) < 1.5 X ULN, aspartate aminotransferase (AST) < 1.5 X ULN.
Have a serum albumin of ≥ 3.0 g/dL
- Must be able to take oral medication without crushing, dissolving or chewing tablets
- Willing to take abiraterone acetate on 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 must be willing and able to adhere to the prohibitions and restrictions
specified in the protocol.
- Written authorization for use and release of health and research study information
has been obtained.
- Patients who have partners of childbearing potential must be willing to use a method
of birth control with adequate barrier protection during the study and for 1 week
after the last dose of abiraterone acetate.
- Surgery or radiation therapy within 2 weeks. Cytotoxic anti-cancer therapy within 3
weeks. Non-cytotoxic anti-cancer therapy within 2 weeks, or 5 half-lives (whichever
is longer) of Study Day 1.
- Use of an investigational therapeutic within 30 days
- Have a history of gastrointestinal disorders (medical disorders or extensive surgery)
that may interfere with the absorption of the study agents
- Prior treatment with cabazitaxel
- Known chronic infection with human immunodeficiency virus (HIV)
- Known active, or symptomatic, brain metastasis
- Blood pressure >140/90 on average (3 separate readings taken at screening visit in a
relaxed clinical environment and averaged)
- History of autoimmune disorder requiring daily corticosteroid therapy of greater than
prednisone 10mg daily, or its equivalent
- Baseline peripheral edema > grade 3
- Pre-existing diarrhea uncontrolled with supportive care; prior hemorrhagic diarrhea
due to ulcerative colitis, inflammatory bowel disease or other cause; active,
uncontrolled peptic ulcer disease even in the setting of proton-pump inhibitor or
- Pre-existing peripheral neuropathy grade > 2
- Documented hypersensitivity (CTCAE grade > 2) to any drug containing polysorbate 80
- Have known allergies, hypersensitivity, or intolerance to abiraterone acetate or
prednisone or their excipients
- Contraindications to steroid use
- Need for medications that strongly induce or inhibit cytochrome P450 3A4 (CYP3A4) or
cytochrome P450 2D6 (CYP2D6) activity
- Serious infection requiring parenteral antibiotics within 14 days of enrollment
- Poorly controlled diabetes (HgbA1C >9)
- 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 Class III-IV heart disease or cardiac ejection fraction
measurement of <50% at baseline.
- Consumption of food or beverages containing grapefruit juice within 7 days of study
- Use of a first-generation anti-androgen such as bicalutamide within 6 weeks of study
drug dosing. Use of flutamide within 4 weeks of study dosing with a continued rise
- Have any condition that, in the opinion of the investigator, would compromise the
well-being of the subject or the study or prevent the subject from meeting or
performing study requirements