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

NCT01637402 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 12551NCI-2012-02079
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Castration Resistant Prostate Cancer

Keywords

CRPC; Prostate; Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Patients With PSA Response From Dose Escalation

  A PSA response for the dose escalation group is defined as a participant with a documented PSA decline after 12 weeks of therapy with standard-dose, then had disease progression, and then achieved a ≥30% PSA decline after 12 weeks from the start of dose escalation therapy.

  Up to 12 weeks from start of dose escalation

Secondary Outcomes (12)

• Number of Participants With Worst-grade, Treatment-related Toxicities for Dose Escalation Group

  Up to 24 months

• Time to PSA Progression for Dose Escalation Cohort

  up to 24 months

• Progression Free Survival for Dose Escalation Cohort

  up to 24 months

• Serum Concentration Levels of Abiraterone Acetate Over Time

  Up to 24 months

• Correlation of Circulating Testosterone Levels at Baseline and Week 12

  Baseline and Week 12

Study Arms (2)

Standard Dose

EXPERIMENTAL

1000 milligrams (mg) abiraterone acetate in combination with prednisone taken once a day until progression defined by RECIST criteria OR by the Prostate Cancer Working Group 2 (PCWG) criteria

Drug: Abiraterone Acetate; Drug: Prednisone

Escalated Dose

EXPERIMENTAL

Participants who progressed on the standard dose will be assigned 1000 milligrams (mg) abiraterone acetate in combination with prednisone taken twice a day for at least 12 weeks until progression as defined by RECIST criteria OR by the Prostate Cancer Working Group 2 (PCWG) criteria

Drug: Abiraterone Acetate; Drug: Prednisone

Interventions

Abiraterone Acetate DRUG

Standard dose participants: 1,000 mg, once daily, oral administration. Dose escalation participants: 1,000 mg, twice daily, oral administration

Also known as: Zytiga

Escalated Dose; Standard Dose

Prednisone DRUG

5 mg, twice daily, oral administration

Escalated Dose; Standard Dose

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Terence Friedlander, MD: lead
• Janssen Biotech, Inc.: collaborator

Study Sites (2)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Oregon Health and Science University

Portland, Oregon, 79239, United States

Location

Related Publications (1)

• Friedlander TW, Graff JN, Zejnullahu K, Anantharaman A, Zhang L, Paz R, Premasekharan G, Russell C, Huang Y, Kim W, Aggarwal RR, Lin AM, Fong L, Alumkal JJ, Beer TM, Sharifi N, Alyamani M, Dittamore R, Small EJ, Paris PL, Ryan CJ. High-Dose Abiraterone Acetate in Men With Castration Resistant Prostate Cancer. Clin Genitourin Cancer. 2017 Dec;15(6):733-741.e1. doi: 10.1016/j.clgc.2017.05.026. Epub 2017 Jun 3.

  PMID: 28655452 RESULT

MeSH Terms

Conditions

Neoplasms

Interventions

Abiraterone Acetate; Prednisone

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes

Limitations and Caveats

Additional accrual to the dose-increased arm was halted early due to lack of efficacy at interim analysis

Results Point of Contact

• Title: Dr. Terry Friedlander, MD
• Organization: University of California, San Francisco

Terence.Friedlander@ucsf.edu

415-514-6380

Study Officials

• Terence Friedlander, MD

  University of California, San Francisco

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Clinical Professor

Model Details: Simon's 2 stage minimax design for accrual.

Study Record Dates

• First Submitted: July 6, 2012
• First Posted: July 11, 2012
• Study Start: March 13, 2013
• Primary Completion: February 27, 2017
• Study Completion: February 27, 2017
• Last Updated: August 17, 2020
• Results First Posted: August 17, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)