Prostatic Neoplasms
Conditions
Keywords
abiraterone, prostate cancer, androgen deprivation therapy
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.
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.
Interventions
DRUGAbiraterone Acetate
Abiraterone Acetate with Prednisone and with Discontinuation of GnRH Analogue
DRUGPrednisone
Abiraterone Acetate with Prednisone and with Discontinuation of GnRH Analogue
Sponsors
Montefiore Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The patient must be able to provide study-specific informed consent prior to study entry * Age ≥ 18 * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 * Pathologically proven diagnosis of prostate adenocarcinoma * Patients must have metastatic prostate cancer * Patients may have mCRPC or may have metastatic castration-sensitive disease. * Patients must be maintained on a GnRH analogue (agonist (leuprolide, goserelin, triptorelin, histrelin, deslorelin) or antagonist (degarelix)) * 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. * Lab values meeting the following criteria * Total testosterone level of \<50 ng/dl * Total bilirubin \< 2.0 X Upper Limit of Normal (ULN) * Aspartate aminotransferase (AST) ≤ 3 X ULN * Alanine aminotransferase (ALT) ≤ 3 X ULN * Absolute Neutrophil Count \> 1.5 K/mm3 * Platelets \> 100 K/mm3 * Hemoglobin ≥ 9.0 g/dL * Calculated creatinine clearance ≥ 30 mL/min
Exclusion criteria
* History of bilateral orchiectomy * History of hypopituitarism * For patients not yet started on abiraterone with prednisone, uncontrolled hypertension (systolic blood pressure \>170 mm Hg or diastolic blood pressure \>100 mm Hg) * 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 * Any other serious illness or medical condition that the principal investigator feels would make the patient a poor candidate for this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Castrate Level of Serum Testosterone | Approximately 24 weeks | The number/percentage of patients with a castrate serum testosterone level, defined as having a serum castrate concentration \<50 ng/dL when Abiraterone acetate plus prednisone (AAP) is used without GnRH analogues in metastatic prostate cancer, will be determined. Results are summarized as a number/percentage of participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Testosterone (T) Levels | Baseline and 6 months, 12 months, 18 months, 24 months, and 30 months following initiation of treatment | Mean serum testosterone (T) concentrations in patients with metastatic prostate cancer treated with abiraterone acetate plus prednisone without a GnRH analogue was measured. Results have been summarized and reported in nanograms/deciliter (ng/dL) using basic descriptive statistics. |
| Serum Luteinizing Hormone (LH) Levels | Baseline and 6 months, 12 months, 18 months, 24 months, and 30 months following initiation of treatment | Mean serum LH levels in patients with metastatic prostate cancer treated with abiraterone acetate plus prednisone without a GnRH analogue was measured. Results have been summarized and reported in International Units/Liter (IU/L) using basic descriptive statistics. |
| Prostate-specific Antigen (PSA) Response | Baseline and 6 months, 12 months, 18 months, 24 months, and 30 months following initiation of treatment | Mean PSA response in patients with metastatic prostate cancer treated with abiraterone acetate plus prednisone without a GnRH analogue was measured. Results have been summarized and reported in ng/mL using basic descriptive statistics. |
| Treatment-related Adverse Events Due to Toxicity | 24 weeks | The number of patients with treatment-related adverse events due to toxicity which lead to discontinuation from the study at 24 weeks is summarized. |
| Radiographic Progression-free Survival (rPFS) | From initiation of treatment to the end of treatment, up to approximately 41 months (~178 weeks) | The duration of time from trial entry until radiographic progression-free survival will be measured/reported. Progression-free survival is an assessment of the average time a patient lives without disease progression, as detected on radiographic imaging scans, or the patient dies from the disease, whichever comes first. Results have been summarized and reported in weeks using basic descriptive statistics. |
| Overall Survival (OS) | From initiation of treatment until the end of treatment, up to approximately 41 months | Overall survival is an assessment of survival from the time initiation of treatment until the time of death to death due to any cause. Results have been summarized and reported in weeks using basic descriptive statistics. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORBenjamin Gartrell, MD
Montefiore Medical Center
Participant flow
Pre-assignment details
35 participants signed informed consent forms to participate in the study. Three participants failed to meet eligibility criteria and were excluded from the protocol and one participant opted not to participate. As a result, 31 participants were enrolled into the study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 69 years |
| Castration-resistant disease as AAP (Abiraterone acetate plus prednisone) indication | 16 Participants |
| Duration of Abiraterone acetate plus Prednisone (AAP) prior to enrollment | 9.2 months |
| Duration of Androgen deprivation therapy (ADT) prior to enrollment | 29.1 months |
| Race/Ethnicity, Customized Hispanic or Latino | 10 Participants |
| Race/Ethnicity, Customized non-Hispanic Black or African-American | 21 Participants |
| Region of Enrollment United States | 31 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 31 |
| other Total, other adverse events | 16 / 31 |
| serious Total, serious adverse events | 0 / 31 |
Outcome results
None listed