Abiraterone With Discontinuation of Gonadotropin-Releasing Hormone Analogues in Metastatic Prostate Cancer

Phase 2

Active, not recruiting

• Conditions: Prostatic Neoplasms
• Interventions: Drug: Abiraterone Acetate; Drug: Prednisone

• Registration Number: NCT03565835
• Lead Sponsor: Montefiore Medical Center

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.

Study Timeline

• Study First Submitted: 2018-05-29
• Study First Submitted QC: 2018-06-11
• Study Start: 2018-06-13
• Study First Posted: 2018-06-21
• Primary Completion: 2021-11-17
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-22
• Last Update Posted: 2022-09-26
• Study Completion: 2023-01-17

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 32

Inclusion Criteria

1. The patient must be able to provide study-specific informed consent prior to study entry

2. Age ≥ 18

3. ECOG (Eastern Cooperative Oncology Group) Performance Status 0-2

4. Pathologically proven diagnosis of prostate adenocarcinoma

5. Patients must have metastatic prostate cancer

6. Patients may have mCRPC or may have metastatic castration-sensitive disease.

7. Patients must be maintained on a GnRH analogue (agonist (leuprolide, goserelin, triptorelin, histrelin, deslorelin) or antagonist (degarelix))

8. 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.

9. Lab values meeting the following criteria

   1. Total testosterone level of <50 ng/dl
   2. Total bilirubin < 2.0 X Upper Limit of Normal (ULN)
   3. Aspartate aminotransferase (AST) ≤ 3 X ULN
   4. Alanine aminotransferase (ALT ) ≤ 3 X ULN
   5. Absolute Neutrophil Count > 1.5 K/mm3
   6. Platelets > 100 K/mm3
   7. Hemoglobin ≥9.0 g/dL
   8. calculated creatinine clearance ≥ 30 mL/min

Exclusion Criteria

10. History of bilateral orchiectomy
11. History of hypopituitarism
12. For patient not yet started on abiraterone with prednisone, uncontrolled hypertension (systolic blood pressure >170 mm Hg or diastolic blood pressure >100 mm Hg)
13. 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
14. Any other serious illness or medical condition that the principal investigator feels would make the patient a poor candidate for this study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Abiraterone and Prednisone without a GnRH Analogue	Abiraterone Acetate	Abiraterone (1000 mg daily) with Prednisone (5 mg) with Discontinuation of GnRH Analogue Injection
Abiraterone and Prednisone without a GnRH Analogue	Prednisone	Abiraterone (1000 mg daily) with Prednisone (5 mg) with Discontinuation of GnRH Analogue Injection

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
Radiographic progression-free survival (rPFS)	24 weeks	To measure the time for trial entry until radiographic progression
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03	24 weeks	To measure the incidence of adverse events
PSA (Prostate-specific antigen) 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.
Median overall survival	24 weeks	To measure the median time from trial entry until death

Trial Locations

Locations (1)

Montefiore Medical Center; 🇺🇸 Bronx, New York, United States