A Phase II Study of Increased-Dose Abiraterone Acetate in Patients With Castration Resistant Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01637402
Recruitment Status : Active, not recruiting
First Posted : July 11, 2012
Last Update Posted : June 8, 2017
Janssen, LP
Information provided by (Responsible Party):
Terence Friedlander, MD, University of California, San Francisco

July 6, 2012
July 11, 2012
June 8, 2017
March 2013
March 2017   (Final data collection date for primary outcome measure)
PSA response proportion to increased-dose Abiraterone Acetate for patients who experienced disease progression following standard dose Abiraterone Acetate therapy [ Time Frame: Estimated up to 24 months ]
Evaualtion at 12 weeks post increased dose therapy initiation and then every 4 weeks until PD#2.
Same as current
Complete list of historical versions of study NCT01637402 on Archive Site
  • Safety of treatment [ Time Frame: Estimated up to 24 months ]
    Toxicities will be graded for management according to NCI-CTCAE version 4.0.
  • Clinical benefit (time to PSA progression and progression free survival) for patients treated with increased dose Abiraterone Acetate [ Time Frame: Estimated up to 24 months ]
  • Serum concentration of Abiraterone Acetate [ Time Frame: Estimated up to 24 months ]
    Pharmacokinetic assessment at the initiation of standard dose therapy, at the time of initial disease progression, at the time of a response to increased-dose Abiraterone Acetate, and at the time of disease progression on increased-dose therapy.
  • Circulating androgen levels [ Time Frame: Estimated up to 24 months ]
    Testosterone, DHEA, DHEA-S and androstenedione will be measured prior to the start of initial Abiraterone Acetate 1000mg mg daily and then every 2 cycles during study therapy.
Same as current
Not Provided
Not Provided
A Phase II Study of Increased-Dose Abiraterone Acetate in Patients With Castration Resistant Prostate Cancer
A Phase II Study of Increased-Dose Abiraterone Acetate in Patients With Castration Resistant Prostate Cancer (CRPC)
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.

This is a phase II multicenter trial of Abiraterone Acetate in patients with progressive prostate cancer despite androgen deprivation with a particular focus on the pharmacokinetic, pharmacodynamic, and pharmacogenomic events occurring at the time of apparent drug resistance. All eligible patients will have baseline (prior to taking the first dose of Abiraterone Acetate 1000mg/daily) measures of routine clinical variables along with measurements of baseline and treatment related changes in testosterone, androgen, and endocrine levels, genotyping of SNPs in the selected enzymes known to be directly inhibited by Abiraterone Acetate, and collection of circulating tumor cells. All patients will be requested to consent for biopsies which will be performed prior to treatment and at the time of disease progression on standard dose Abiraterone Acetate therapy. These biopsies will be analyzed for expression of an AR-signature as well as for microarray analysis to explore changes in methylation, and expression of CYP17A1 and other androgen synthesis genes.

Subjects will then begin daily oral therapy with Abiraterone Acetate 1000mg po daily with physiologic prednisone 5mg BID replacement. No food should be consumed for at least 2 hours before the dose of Abiraterone Acetate and for at least 1 hour after the dose of Abiraterone Acetate is taken. PSA will be followed monthly. Abiraterone Acetate will be supplied by Janssen Services. At the end of the first month, the third month, and then every three months thereafter, Abiraterone Acetate, testosterone, and androgen levels will be followed. Subjects not achieving a greater than or equal to 30% PSA decline at 12 weeks will be taken off study. At the time of progression (defined by RECIST criteria OR by the Prostate Cancer Working Group 2 (PCWG) criteria as a 25% increase in PSA above the nadir and an increase in the absolute value PSA of at least 2ng/dl or back to baseline confirmed at least 2 weeks afterward) for subjects who achieved an initial greater than or equal to 30% PSA decline (referred to as Progressive Disease (PD) #1), subjects will begin taking Abiraterone Acetate 1000 mg po BID. Patients will continue to take prednisone 5mg BID and will continue this therapy until a second progression at which point they will be withdrawn from the study. While 1000 mg po BID is not the FDA recommended dose, it is the dose to be investigated in this study.

Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Castration Resistant Prostate Cancer
  • Drug: Abiraterone Acetate

    Standard dose: 1,000 mg, once daily, oral administration

    Increased dose: 1,000 mg, twice daily, oral administration

    Other Name: Zytiga
  • Drug: Prednisone
    5 mg, twice daily, oral administration
Experimental: Abiraterone Acetate in combination with prednisone
  • Drug: Abiraterone Acetate
  • Drug: Prednisone
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Active, not recruiting
Same as current
December 2017
March 2017   (Final data collection date for primary outcome measure)

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 mEq/L
  • Have aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin levels < 1.5 x 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 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 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 pts without PSA decline on an anti-androgen or in those in whom a PSA response lasted < 3 months.
  • 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.
Sexes Eligible for Study: Male
18 Years and older   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
United States
UCSF Protocol No. 12551
Not Provided
Not Provided
Terence Friedlander, MD, University of California, San Francisco
Terence Friedlander, MD
Janssen, LP
Study Chair: Terence Friedlander, MD University of California, San Francisco
University of California, San Francisco
June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP