Apalutamide and Abiraterone Acetate in African American and Caucasian Men With Metastatic Castrate Resistant Prostate Cancer
- Conditions
- Prostate Cancer
- Interventions
- Registration Number
- NCT03098836
- Lead Sponsor
- Daniel George, MD
- Brief Summary
The primary goal is to prospectively estimate the median PFS of African American and Caucasian men with mCRPC taking apalutamide, abiraterone acetate, and prednisone. Secondary objectives include: PSA kinetics: to determine the duration of PSA response, time to nadir, and percent of men who achieve a PSA \< 0.1; Radiographic assessments: to estimate the rate of objective response and incidence of bone flares; Safety (NCI CTC v4.0) and tolerability, particularly incidence and grade of hypertension in the two populations.
This is a non-comparative pilot open-label, parallel arm, multicenter study of apalutamide and abiraterone acetate in African American and Caucasian men with mCRPC. It is anticipated that 3 additional sites will be needed to accrue 100 subjects (50 African American and 50 Caucasian) over a 24 month accrual period. The study agents will be administerd at the following doses: apalutamide 240mg orally once daily, abiraterone acetate 1000mg orally once daily, and prednisone 5 mg BID in 4-week cycles throughout the treatment period.
Fifty (50) patients will be enrolled in each group (AA and Caucasians). The proportion of patients who experience PSA decline of 30%, 50% and 90% will be estimated with exact 95% confidence intervals based on the binomial distribution will be computed. In addition, post therapy changes in PSA will be explored as a continuous outcome. The Kaplan-Meier product limit method will be used to estimate the rPFS, biochemical PFS and overall survival distributions.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 93
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Male, age ≥ 18 years
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Karnofsky performance status ≥ 70 (Appendix 1)
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Life expectancy of ≥ 12 months as determined by treating investigator
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Written Authorization for Use and Release of Health and Research Study Information (HIPAA authorization per institutional requirements)
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Willing/able to adhere to the prohibitions and restrictions specified in this protocol
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Willing to take abiraterone acetate on an empty stomach, and should be able to swallow tablets whole, without crushing/chewing tablets. Must have the ability to swallow, retain, and absorb oral medication.
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Medications known to lower the seizure threshold (see list under prohibited meds, appendix 2) must be discontinued or substituted at least 4 weeks prior to study entry
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Agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. Must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug. Abstinence is an acceptable method of birth control.
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Adequate bone marrow function as shown by: ANC ≥ 1.0 x 109/L, Platelets ≥ 100 x 109/L, Hb≥9 g/dL, (independent of transfusion and/or growth factors within 3 months prior to Cycle 1 Day 1)
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Serum potassium ≥ 3.5 mEq/L
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Serum albumin of ≥ 3.0 g/dl
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AST/SGOT and ALT/SGPT <2.5 x Institutional Upper Limit of Normal (ULN)
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Serum total bilirubin ≤ 1.5 x Institutional ULN (Note: In subjects with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN, subject may be eligible)
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GFR ≥45 mL/min
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Histologically confirmed diagnosis of adenocarcinoma of the prostate. Histologic variants of prostate cancer comprising of >50% of the tumor including neuroendocrine features and small cell carcinoma of the prostate are excluded.
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Radiographic evidence of metastatic disease based on RECIST 1.1 Criteria OR by prostate cancer-specific PET imaging. Evaluable non-target lesions and/or bone only metastasis are permitted per RECIST 1.1 and PCWG3 guidelines. Non-target, pathological lymph nodes ≥ 10 mm and less than 15 mm in the short axis are permitted.
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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.
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PSA ≥ 2.0 ng/mL
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Evidence of castration resistant disease in the setting of ongoing ADT (medical or surgical) as evidenced by one of the following:
- Absolute rise in PSA of 2.0 ng/mL or an increase >25% from the nadir, minimum 2 consecutive rising PSA levels with an interval of ≥ 1 week between each PSA level, OR
- CT or MRI based evidence of disease progression (soft tissue, nodal or visceral disease progression) according to PCWG3 criteria or RECIST 1.1 criteria, OR
- At least 1 new bone scan lesion as compared to the most immediate prior radiologic studies.
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A minimum of 2 weeks elapsed off of antiandrogen therapy prior to start of study drug (i.e. flutamide, nilutamide, bicalutamide.)
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A minimum of 2 weeks elapsed off of sipuleucel-T and radiation therapy prior to start of study drug
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A minimum of 4 weeks from any major surgery prior to start of study drug.
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Self-reported race of either African American or Caucasian.
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Ability to understand and the willingness to sign a written informed consent document. If the subject is unable to understand the consent due to comorbidity, such as Alzheimer's disease, consent by a legally authorized representative and assent by the subject will be obtained.
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Prior treatment with abiraterone acetate, enzalutamide, apalutamide (ARN-509), galaterone (TOK-001), orteronel (TAK-700), or similar agent
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Active infection or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated
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Active or symptomatic infection including HIV, viral hepatitis or chronic liver disease
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Any chronic medical condition requiring a higher dose of corticosteroid than 5mg prednisone/prednisolone bid
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Have known allergies, hypersensitivity, or intolerance to abiraterone acetate, apalutamide or prednisone or their excipients.
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Pathological finding consistent with small cell carcinoma of the prostate
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Symptomatic liver or visceral organ metastasis
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Have a history of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agents
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Known brain metastasis
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Prior cytotoxic chemotherapy or biologic therapy for the treatment of CRPC. Note: sipulecel-T is permitted with a 2-week washout.
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Previously treated with ketoconazole for prostate cancer for greater than 7 days
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Prior systemic treatment with an azole anti-fungal drug (e.g. fluconazole, itraconazole) within 4 weeks of Cycle 1, Day 1.
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Uncontrolled hypertension (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg). Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment
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Poorly controlled diabetes, FBS ≥200 mg/dL
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History of pituitary or adrenal dysfunction
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Symptomatic Atrial Fibrillation, or other symptomatic cardiac arrhythmia
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Other malignancy, except non-melanoma skin cancer, with a ≥ 30% probability of recurrence within 24 months
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History of any of the following:
- Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 6 months of Cycle 1 Day 1, brain arteriovenous malformation, Schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy)
- Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to first dose of study drug. Venous thrombolic events within 6 months are permitted IF they are not attributed to prostate cancer (in the opinion of the treating physician).
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Avoid concomitant strong CYP3A4 inducers during abiraterone acetate treatment.
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Avoid co-administration of abiraterone acetate with CYP2D6 substrates that have a narrow therapeutic index. If an alternative treatment cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate
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Baseline moderate or severe hepatic impairment (Child Pugh Class B & C)
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Use of herbal products that may decrease PSA levels (i.e., saw palmetto) refer to section 8.3.2 (no washout period required)
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Administration of an investigational therapeutic within 30 days prior to Cycle 1, Day 1
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Any condition which, in the opinion of the investigator, would preclude participation in this trial
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description African American ARN-509 - African American Abiraterone Acetate - Caucasian ARN-509 - Caucasian Abiraterone Acetate - Caucasian Prednisone - African American Prednisone -
- Primary Outcome Measures
Name Time Method Median radiographic progression free survival (PFS) every 12 weeks, up to 4 years Radiographic PFS based on PCWG2 criteria or based on the onset of a skeletal related event. Imaging obtained every 12 weeks.
- Secondary Outcome Measures
Name Time Method Change in radiologic response rates every 12 weeks, up to 2 years RECIST 1.1 defined radiologic response rates and incidence of bone flares
Change in PSA response every 4 weeks, up to 4 years Duration of PSA response
Time to PSA nadir every 4 weeks, up to 2 years Time to PSA nadir
Percent of men who achieve a PSA < 0.1 every 4 weeks, up to 2 years Percent of men who achieve a PSA \< 0.1
Number of adverse events up to 2 years Safety (NCI CTC v4.0) and tolerability, particularly incidence and grade of hypertension in the two populations
Overall survival every 6 months, up to 4 years Survival of subjects over the time the study is ongoing
Trial Locations
- Locations (13)
UNC Lineberger Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Southeastern Regional
🇺🇸Lumberton, North Carolina, United States
Spartanburg Regional
🇺🇸Spartanburg, South Carolina, United States
Chesapeake Urology Associates
🇺🇸Baltimore, Maryland, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Tulane University
🇺🇸New Orleans, Louisiana, United States
Johnston Hematology and Oncology of Clayton
🇺🇸Clayton, North Carolina, United States
Scotland Memorial Hospital
🇺🇸Laurinburg, North Carolina, United States
Johnston Memorial Hospital
🇺🇸Smithfield, North Carolina, United States
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
Duke Cancer Center Cary
🇺🇸Cary, North Carolina, United States
Maria Parham Hospital
🇺🇸Henderson, North Carolina, United States