Abiraterone With Discontinuation of Gonadotropin-Releasing Hormone Analogues in Metastatic Prostate Cancer
Study Details
Study Description
Brief Summary
The goal of this study is to find out if patients with prostate cancer being treated with the medications abiraterone and prednisone can discontinue hormone injections (examples include leuprolide, goserelin, triptorelin and degarelix). Abiraterone and prednisone are pills used to treat patients with prostate cancer. When abiraterone and prednisone are used, hormone injections are usually continued to maintain a low testosterone level in the blood. This study is being done to find out if testosterone in the blood will stay low while abiraterone and prednisone are used without continued hormone injections.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Abiraterone inhibits the CYP17A enzyme, which is a critical enzyme in androgen biosynthesis. Abiraterone has regulatory approval in metastatic castration-resistant prostate cancer (mCRPC) in both chemotherapy-naïve and in the post-docetaxel setting based upon results from two randomized phase III studies. Abiraterone is also proven to extend survival in the metastatic, hormone-naïve population based on two phase III studies. Abiraterone is a castrating agent, but, other than a small first in human study, all clinical studies have been done in conjunction with gonadotropin-releasing hormone (GnRH) analogues. Maintaining castrate level of serum testosterone is critical in the treatment of metastatic prostate cancer. It is unknown if GnRH analogues must be continued to maintain castrate levels of serum testosterone in patients treated with abiraterone.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Abiraterone and Prednisone without a GnRH Analogue Abiraterone (1000 mg daily) with Prednisone (5 mg) with Discontinuation of GnRH Analogue Injection |
Drug: Abiraterone Acetate
Abiraterone Acectate with Prednisone and with Discontinuation of GnRH Analogue
Drug: Prednisone
Abiraterone Acectate with Prednisone and with Discontinuation of GnRH Analogue
|
Outcome Measures
Primary Outcome Measures
- Proportion of patients with a non-castrate (>50 ng/dl) serum testosterone [24 weeks]
To assess the proportion of patients with a non-castrate testosterone level (>50 ng/dl) when abiraterone acetate plus prednisone is used without GnRH analogues in metastatic prostate cancer.
Secondary Outcome Measures
- Luteinizing hormone (LH) level after discontinuation of GnRH analogue [24 weeks]
To measure serum LH level in patients with metastatic prostate cancer treated with abiraterone acetate plus prednisone without a GnRH analogue.
- PSA response rate [24 weeks]
To measure PSA response rate and in patient with metastatic prostate cancer treated with abiraterone acetate plus prednisone without a GnRH analogue.
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [24 weeks]
To measure the incidence of adverse events
- Radiographic progression-free survival (rPFS) [24 weeks]
To measure the time for trial entry until radiographic progression
- Median overall survival [24 weeks]
To measure the median time from trial entry until death
Eligibility Criteria
Criteria
Inclusion Criteria:
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The patient must be able to provide study-specific informed consent prior to study entry
-
Age ≥ 18
-
ECOG Performance Status 0-2
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Pathologically proven diagnosis of prostate adenocarcinoma
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Patients must have metastatic prostate cancer
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Patients may have mCRPC or may have metastatic castration-sensitive disease.
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Patients must be maintained on a GnRH analogue (agonist (leuprolide, goserelin, triptorelin, histerelin, deslorin) or antagonist (degarelix))
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The patient and the investigator have decided that the next line of cancer therapy will be abiraterone plus prednisone and the initial dose of abiraterone will be 1000 mg daily. Or patients may already be on abiraterone with prednisone at a dose of 1000 mg daily along with a GnRH analogue.
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Lab values meeting the following criteria
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Total testosterone level of <50 ng/dl
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Total bilirubin < 2.0 X Upper Limit of Normal (ULN)
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Aspartate aminotransferase (AST) ≤ 3 X ULN
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Alanine aminotransferase (ALT ) ≤ 3 X ULN
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Absolute Neutrophil Count > 1.5 K/mm3
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Platelets > 100 K/mm3
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Hemoglobin ≥9.0 g/dL
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calculated creatinine clearance ≥ 30 mL/min
Exclusion Criteria:
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History of bilateral orchiectomy
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History of hypopituitarism
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For patient not yet started on abiraterone with prednisone, uncontrolled hypertension (systolic blood pressure >170 mm Hg or diastolic blood pressure >100 mm Hg)
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Patients must not have New York Heart Association Class III or IV heart failure at the time of screening. Patients must not have any unstable angina, myocardial infarction, or serious uncontrolled cardiac arrhythmia within 6 months prior to registration
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Any other serious illness or medical condition that the principal investigator feels would make the patient a poor candidate for this study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Montefiore Medical Center | Bronx | New York | United States | 10461 |
Sponsors and Collaborators
- Montefiore Medical Center
Investigators
- Principal Investigator: Benjamin Gartrell, MD, Montefiore Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2017-8506