Abiraterone Race in Metastatic Castrate-resistant Prostate Cancer

• ClinicalTrials.gov Identifier: NCT01940276
• Recruitment Status: Completed
• First Posted: September 12, 2013
• Results First Posted: December 9, 2020
• Last Update Posted: December 9, 2020
• Sponsor: Duke University
• Information provided by (Responsible Party): Duke University

Study Description

Brief Summary:

The primary goal is to prospectively estimate the median radiographic PFS of African American and Caucasian men with mCRPC to abiraterone acetate and prednisone.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Drug: Abiraterone acetate; Drug: Prednisone	Phase 2

Detailed Description:

This is a non-comparative pilot open-label, parallel arm, multicenter study of abiraterone acetate in African American and Caucasian men with mCRPC. Patients will self-report on race and 50 patients will be enrolled into each group. Patients will be treated on open-label treatment until evidence of disease progression as defined by Prostate Cancer Working Group Two (PCWG2) definition or until two years at which point they will roll over to the standard of care at that time. The study agent abiraterone acetate will be administered by the patient at a dose of 1000mg orally once daily with prednisone 5 mg BID in 4-week cycles throughout the treatment period.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Open-label, Parallel Group Study of Abiraterone Acetate Plus Prednisone in African American and Caucasian Men With Metastatic Castrate-resistant Prostate Cancer
• Actual Study Start Date: October 2013
• Actual Primary Completion Date: October 8, 2019
• Actual Study Completion Date: October 8, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Abiraterone Acetate and Prednisone; abiraterone acetate will be administered by the patient at a dose of 1000mg orally once daily with prednisone 5 mg BID in 4-week cycles	Drug: Abiraterone acetate; Other Name: Zytiga; Drug: Prednisone

Outcome Measures

Primary Outcome Measures :

1. Median Radiographic Progression Free Survival (PFS) [ Time Frame: up to 2 years ]
   Time in months from the start of study treatment to the date of first progression according to Prostate Cancer Working Group 2 criteria, or to death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median rPFS was estimated using a Kaplan-Meier curve.

Secondary Outcome Measures :

1. Change in PSA Response [ Time Frame: Baseline and up to 2 years ]
   Percent of men with Prostate Specific Antigen (PSA) declines > 30%, > 50% and > 90%
2. Median Time to PSA Progression [ Time Frame: up to 2 years ]
   Time to PSA progression as defined by PCWG 2 criteria is the date that a 25% or greater increase and an absolute increase of 2 ng/mL or more from the nadir is documented, which is confirmed by a second value obtained 3 or more weeks later.
3. Number of Men With PSA Decline to < 0.1 and < 0.2 ng/ml [ Time Frame: up to 2 years ]
   Number of men who achieve a PSA decline to < 0.1 and < 0.2 ng/ml
4. Percent of Subjects Experiencing Hypertension [ Time Frame: up to 2 years ]
   Incidence and grade of hypertension in the two populations. (Grade 1: Systolic BP 120 to 139 mmHg or diastolic BP 80 to 89 mmHg, Grade 2: Systolic BP 140 to 159 mmHg or diastolic BP 90 to 99 mmHg, Grade 3: Systolic BP ≥160 mmHg or diastolic BP ≥100 mmHg, Grade 4: Life-threatening consequences, urgent intervention indicated)
5. Overall Survival [ Time Frame: up to 3 years ]
   Length of patient's life after starting study

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Male, age ≥ 18 years
• Karnofsky performance status ≥ 70
• Life expectancy of ≥ 12 months
• 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, and should be able to swallow tablets whole, without crushing/chewing tablets
• 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 dose of abiraterone acetate
• Adequate laboratory parameters
• Histologically confirmed diagnosis of adenocarcinoma of the prostate. Histologic variants of prostate cancer, including neuroendocrine features and small cell carcinoma of the prostate are excluded
• Radiographic evidence of metastatic disease; evaluable non-target lesions and/or bone only metastasis are permitted
• Ongoing ADT using an LHRH agonist (e.g. leuprolide, goserelin) or antagonist (e.g. degarelix) must continue on therapy unless prior bilateral orchiectomy has been performed. Screening serum testosterone must be <50 ng/dl
• PSA ≥ 2.0 ng/mL

• Evidence of of castration resistant disease on ADT as evidenced by one of the following:

  • Absolute rise in PSA of 2.0 ng/mL or greater, minimum 2 consecutive rising PSA levels with an interval of ≥ 1 week between each PSA level, OR
  • 2 consecutive PSA levels 50% or greater above the PSA nadir achieved on ADT and separated at least 1 week apart, OR
  • CT or MRI based evidence of disease progression (soft tissue, nodal or visceral disease progression) according to modified PCWG2 criteria or modified RECIST 1.1 criteria, or at least 1 new bone scan lesion as compared to the most immediate prior radiologic studies)
• A minimum of 2 weeks elapsed off of antiandrogen therapy prior to start of study drug (i.e. flutamide, nilutamide, bicalutamide)
• A minimum of 4 weeks elapsed off of sipuleucel-T prior to start of study drug
• A minimum of 4 weeks from any major surgery prior to start of study drug
• Self-reported race of either African American or Caucasian
• Ability to swallow, retain, and absorb oral medication

Exclusion Criteria:

• Prior treatment with abiraterone acetate or enzalutamide
• Active infection or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated
• Any chronic medical condition requiring a higher dose of corticosteroid than 5mg prednisone/prednisolone bid
• Have known allergies, hypersensitivity, or intolerance to abiraterone acetate or prednisone or their excipients
• Pathological finding consistent with small cell carcinoma of the prostate
• Symptomatic Liver or visceral organ metastasis
• Have a history of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agents
• Known brain metastasis
• Prior cytotoxic chemotherapy or biologic therapy for the treatment of CRPC
• Previously treated with ketoconazole for prostate cancer for greater than 7 days
• Prior systemic treatment with an azole drug (e.g. fluconazole, itraconazole) within 4 weeks of Cycle 1, Day 1
• 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.
• Poorly controlled diabetes
• 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 therapy
• Other malignancy, except non-melanoma skin cancer, with a ≥ 30% probability of recurrence within 24 months
• Administration of an investigational therapeutic within 30 days of Cycle 1, Day 1
• Any condition which, in the opinion of the investigator, would preclude participation in this trial

Contacts and Locations

Locations

United States, Alabama

Birmingham VA Medical Center

Birmingham, Alabama, United States, 35233

United States, Louisiana

Tulane Cancer Center

New Orleans, Louisiana, United States, 70112

United States, Michigan

Karmanos Cancer Institute

Detroit, Michigan, United States, 48201

United States, North Carolina

University of North Carolina

Chapel Hill, North Carolina, United States, 27599

Duke University Medical Center

Durham, North Carolina, United States, 27710

Maria Parham Medical Center

Henderson, North Carolina, United States, 27536

Scotland Memorial Hospital

Laurinburg, North Carolina, United States, 28352

Southeastern Regional

Lumberton, North Carolina, United States, 28359

Duke Raleigh Hospital

Raleigh, North Carolina, United States, 27609

W. G. 'Bill' Hefner VA Medical Center

Salisbury, North Carolina, United States, 28144

Johnston Memorial Hospital

Smithfield, North Carolina, United States, 27577

Wake Forest University

Winston-Salem, North Carolina, United States, 27157

United States, South Carolina

Spartanburg Regional

Spartanburg, South Carolina, United States, 29303

United States, Virginia

Virginia Oncology Associates

Hampton, Virginia, United States, 23666

Sponsors and Collaborators

Duke University

Investigators

• Principal Investigator: Daniel George, MD; Duke University

  Study Documents (Full-Text)

Documents provided by Duke University:

Study Protocol and Statistical Analysis Plan  [PDF] April 24, 2018

Informed Consent Form  [PDF] March 3, 2018

More Information

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT01940276
• Other Study ID Numbers: Pro00046383; 212082PCR2018 ( Other Identifier: Janssen )
• First Posted: September 12, 2013
• Results First Posted: December 9, 2020
• Last Update Posted: December 9, 2020
• Last Verified: November 2020

Keywords provided by Duke University:

Prostate cancer; metastatic; castrate resistant; abiraterone acetate; prednisone; metastatic prostate cancer

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases; Prednisone; Abiraterone Acetate; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors