NCT03336983

Luteinizing Hormone-releasing Hormone Analogue and Enzalutamide +/- Zoledronic Acid in Prostate Cancer Patients

Bone Response After Luteinizing Hormone-releasing Hormone Analogue and Enzalutamide +/- Zoledronic Acid in Prostate Cancer Patients With Hormone Sensitive Metastatic Bone Disease: a Prospective, Phase II, Randomized, Multicenter Study

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 126 (actual)
• Sponsor: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study was undertaken to evaluate bone response in metastatic prostate cancer patients treated with Enzalutamide with or without Zoledronic Acid in combination with luteinizing hormone-releasing hormone (LHRH) analogue with the use of Whole Boby (WB) DW-MRI.

Detailed description

Most men with fatal prostate cancer develop bone metastases and bone is often the dominant or the only site of metastatic disease. Bone metastases are an important cause of morbidity since they are associated with skeletal related events (SREs) including pathologic fractures, spinal cord compression, and need for surgery or radiation therapy to bone. Osteoclast-mediated bone destruction is the key pathologic mechanism for SREs in prostate cancer and other malignancies. Zoledronic acid (ZA) is a potent inhibitors of osteoclast-mediated bone resorption. ZA has demonstrated to be effective in preventing SREs in patients with castrate resistant disease; however, its efficacy in hormone naïve disease is uncertain. In the last few years new drugs targeting directly the androgen receptor such as Enzalutamide have shown to be very effective in terms of survival prolongation in the management of castration resistant disease and the efficacy in hormone naïve patients is currently under investigation. Interestingly, the results of a large scale, prospective, randomized clinical trial have shown that Enzalutamide administration is also associated with a reduction in the risk of SREs and this raises the question of the usefulness of the addition of bone resorption inhibitors to Enzalutamide. The evaluation of bone response of antineoplastic therapies has always been difficult in metastatic bone prostate cancer patients due to their osteoblastic nature. Whole body diffusion-weighted (DW) MRI has been recently proposed as new imaging tool for grading treatment response in patients with skeletal metastases from prostate cancer. According to the literature data DW images can allow the identification of bone marrow infiltration and tumor necrosis induced by treatment. In addition, this technique allows to monitor the bone marrow restoration. This, this technique was selected to evaluate bone response in metastatic prostate cancer patients treated with Enzalutamide with or without Zoledronic Acid in combination with LHRH-A. Moreover, since androgen-receptor isoform encoded by splice variant 7 (AR-V7) is an androgens' receptor variant that could have a potential clinical utility as a prognostic factor and predictive marker of therapy response, an ancillary study will be conducted to evaluate ARV7 expression in Circulating Tumor Cells (CTC).

Conditions

• Prostate Cancer
• Bone Metastases

Interventions

Type	Name	Description
DRUG	Zoledronic Acid	Prostate cancer patients with hormone sensitive metastatic bone disease will be treated with LHRH-A + Enzalutamide in the presence or absence of Zoledronic Acid
DRUG	Enzalutamide	Patients from both arms will be treated with LHRH-A + Enzalutamide

Timeline

• Start date: 2017-12-01
• Primary completion: 2022-06-30
• Completion: 2023-04-01
• First posted: 2017-11-08
• Last updated: 2024-08-01

Locations

1 site across 1 country: Italy