Phase II Clinical Trial of Abiraterone Acetate Without Exogenous Glucocorticoids in Men With Castration-resistant Prostate Cancer With Correlative Assessment of Hormone Intermediates.
Phase: Phase 2
Diagnosis: Prostate Cancer
NCT ID: NCT02025010
(View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 13-449
This study is comparing the safety and effectiveness of abiraterone acetate alone, followed by the addition of prednisone (when the participant's disease worsens or the physician feels it would lessen symptoms of toxicity) versus the current approved treatment regimen which involves the concomitant use of prednisone in conjunction with abiraterone acetate. Additionally, this study is also examining why participants stop responding to treatment with abiraterone acetate by evaluating blood and tissue.
Dana-Farber Cancer Institute, Brigham and Women's Hospital
Mary-Ellen Taplin, MD,
Dana-Farber Cancer Institute
Dana-Farber Cancer Institute:
Amanda Fredericks, 617-632-5514,
Dana-Farber Cancer Institute:
Judith Prisby, 617-632-5068,
Dana-Farber Cancer Institute:
Meghara Walsh, 617-632-5264,
- Participants must meet the following criteria on screening examination to be eligible
to participate in the study:
- Be a male ≥ 18 years of age.
- Participants must have histologically or cytologically confirmed adenocarcinoma of
the prostate without >50% neuroendocrine differentiation or small cell histology.
- Participants must have progressive disease as defined by one or more of the
- Castrate resistant disease as defined by Prostate cancer working Group (PCWG).
Participants must have a rise in PSA on two successive determinations at least one
week apart and PSA levels ≥ 2 ng/ml (only the screening PSA needs to be ≥ 2 ng/ml)
and testosterone levels < 50 ng/dL.
- Soft tissue progression defined by Response Evaluation Criteria In Solid Tumors
- Bone disease progression defined by Prostate Cancer Clinical Trials Working Group 2
(PCWG2) with two or more new lesions on bone scan.
- Castration-resistant prostate cancer (CRPC) with metastatic disease with at least one
site of metastatic disease must be amenable to needle biopsy. Soft tissue biopsy
sites include: lymph node or visceral metastases. Bone sites include lumbar
vertebrae, pelvic bones and long bones. Excluded sites are thoracic, cervical
vertebrae, skull and rib lesions. Biopsy site will be selected with guidance of
interventional radiologist determining best site to optimize balance of obtaining
useful tissue for analysis and minimizing risk.
- Participants without orchiectomy must be maintained on Luteinizing hormone-releasing
hormone (LHRH) agonist/antagonist therapy.
- Participants may have had any number of previous hormonal therapies (antiandrogens
including enzalutamide, steroids, estrogens, finasteride, dutasteride, ketoconazole)
provided these were discontinued ≥ 4 weeks before starting the trial.
- Participants may have had up to two previous cytotoxic therapeutic regimens provided
these were discontinued ≥ 4 weeks before starting the trial.
- At least a 4 week interval from previous prostate cancer treatment other than LHRH
agonist/antagonist therapy or bisphosphonates to the start of protocol therapy.
- Participants receiving bisphosphonates therapy can be maintained on this therapy. If
participants have not started bisphosphonates, it is recommended that they start
treatment after the first biopsy.
- Eastern Cooperative Oncology Group (ECOG) performance status < 2 (Karnofsky >60%, see
Participants must have normal organ and marrow function as defined below:
- Platelets > 50,000/microliter (mcL)
- Serum potassium ≥ 3.5 mmol/L (independent of potassium supplementation)
- Serum albumin ≥ 3.0 g/dL
- Aspartate transaminase (AST), Alanine transaminase (ALT), and total bilirubin ≤ 1.5 x
Institutional Upper Limit of Normal (ULN).
- Partial thromboplastin time (PTT) ≤ 60, International Normalized Ratio (INR) ≤ 1.5
Institutional ULN unless on warfarin therapy (investigator would need to determine if
safe for participant to stop warfarin prior to biopsy)
- Controlled blood pressure (systolic blood pressure < 140 and diastolic blood pressure
<90) on no more than three anti-hypertensive agents. Drug formulations containing two
or more anti-hypertensive agents will be counted based on the number of active agents
in each formulation.
- EKG showing a normal QTc interval (QTc < 450 msec).
- Left ventricular ejection fraction ≥ 50%.
- 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
- Be willing/able to adhere to the prohibitions and restrictions specified in this
- Written Authorization for Use and Release of Health and Research Study Information
(US sites only) has been obtained.
- Able to swallow the study drug whole as a tablet.
- Willing to take AA on an empty stomach; no food should be consumed at least two hours
before and for at least one hour after the dose AA is taken.
- Participants 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 PI during the treatment period and for 1 week after last dose of
- Participants who exhibit any of the following conditions at screening will not be
eligible for admission into the study.
- Uncontrolled illness including, but not limited to ongoing or active infection,
symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia,
or psychiatric illness/social situations that would limit compliance with study
requirements or would make prednisone/prednisolone (corticosteroid) use
- 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 or IV heart disease or cardiac ejection
fraction measurement of < 50 % at baseline.
- Thromboembolism within 6 months of Cycle 1, Day 1.
- Severe hepatic impairment (Child-Pugh Class C).
- History of pituitary or adrenal dysfunction.
- Poorly controlled diabetes.
- History of gastrointestinal disorders (medical disorders or extensive surgery) which
may interfere with the absorption of the study drug.
- Have a pre-existing condition that warrants long-term corticosteroid use.
- Individuals with a history of a different malignancy are ineligible except for the
following circumstances: 1) individuals with a history of other malignancies are
eligible if they have been disease-free for at least 5 years and are deemed by the
investigator to be at low risk for recurrence of that malignancy, or 2) individuals
with the following cancers are eligible if diagnosed and treated within the past 5
years: superficial bladder cancer, basal cell or squamous cell carcinoma of the skin.
- Known brain metastasis.
- Prior therapy with AA.
- Have known allergies, hypersensitivity, or intolerance to AA or prednisone or their
- Surgery or local prostatic intervention within 30 days of the first dose. In
addition, any clinically relevant issues from the surgery must have resolved prior to
Cycle 1, Day 1.
- Major surgery or radiation therapy within 4 weeks of Cycle 1, Day 1.
- Strontium-89 or samarium-153 therapy within 4 weeks of Cycle 1, Day 1.
- Radiotherapy, chemotherapy or immunotherapy within 4 weeks, or single fraction of
palliative radiotherapy within 14 days of administration of Cycle 1, Day 1.
- Current enrollment in an investigational drug or device study or participation in
such a study within 30 days of Cycle 1, Day 1.
- Any acute toxicities due to prior chemotherapy and/or radiotherapy that have not
resolved to a NCI Common Toxicity Criteria for Adverse Effects (CTCAE) version 4
grade of ≤ 1. Chemotherapy induced alopecia and grade 2 peripheral neuropathy are
- Condition or situation which, in the investigator's opinion, may put the participant
at significant risk, may confound the study results, or may interfere significantly
with participant's participation in the study.
- Individuals not willing to comply with the procedural requirements of this protocol.
- HIV-positive individuals on combination antiretroviral therapy are ineligible because
of the potential for pharmacokinetic interactions with AA.