PSMA-targeted Therapy + Androgen Suppression for Prostate Cancer

(SPARKLE Trial)

This trial tests new combinations of treatments for prostate cancer that has spread to a few locations or returned after some time. Researchers aim to determine if adding the radiotherapy drug 177Lu-PSMA-617 to standard hormone therapies (which lower male hormones like testosterone) increases effectiveness. Some participants will also take additional medications, such as Leuprolide Acetate (a hormone therapy), Abiraterone Acetate (which blocks hormone production), and Prednisone (which reduces inflammation). Men with prostate cancer that has spread to fewer than 10 spots or returned after treatment might be suitable candidates. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Previous studies have shown that lutetium Lu 177 vipivotide tetraxetan is safe. Most patients tolerated it well, with some experiencing side effects, but serious reactions were rare, occurring in only 2.8% of cases. This drug targets prostate cancer cells and delivers radiation directly to them, aiming to minimize harm to nearby healthy tissue.

Abiraterone acetate, usually combined with prednisone, is already approved for other types of prostate cancer. It blocks the production of male hormones like testosterone, which prostate cancer cells need to grow. Its safety is well-documented, and it is considered safe when properly monitored.

Leuprolide acetate, another treatment in this study, is a type of hormone therapy. It is commonly used in prostate cancer treatment and is generally well-tolerated. It works by stopping the body from making testosterone, which can help slow the growth of cancer cells.

Researchers are excited about these treatments for prostate cancer because they incorporate a novel approach with PSMA-targeted therapy. Unlike traditional treatments that primarily focus on androgen suppression, the investigational drug 177Lu-PSMA-617 targets the prostate-specific membrane antigen (PSMA), a protein highly expressed in prostate cancer cells, and delivers radiation directly to them. This targeted approach could potentially enhance treatment efficacy while minimizing damage to healthy tissues. Combined with androgen deprivation therapy and additional medications like abiraterone acetate and prednisone, these treatments aim to improve outcomes for patients by tackling the cancer from multiple fronts.

Research has shown that 177Lu-PSMA-617 can help prostate cancer patients live longer. It significantly delays symptoms from cancer spreading to the bones and extends life by about four months. Approximately 69% of patients experienced a significant drop in PSA levels, which indicate prostate cancer activity. In this trial, some participants will receive 177Lu-PSMA-617 alongside leuprolide acetate, while others will receive it in combination with abiraterone acetate and prednisone. Abiraterone acetate blocks male hormones like testosterone, which prostate cancer cells need to grow. Overall, these treatments show promise in fighting hormone-sensitive prostate cancer.³⁶⁷⁸⁹