Targeting Androgen Signaling in Urothelial Cell Carcinoma - Neoadjuvant — TASUC-Neo  

Urothelial Carcinoma Bladder Clinical Trial

Official title: Targeting Androgen Signaling in Urothelial Cell Carcinoma - Neoadjuvant (TASUC-Neo): A Pilot Study of Degarelix in Combination With Neoadjuvant Gemcitabine and Cisplatin in Muscle-Invasive Urothelial Cell Carcinoma of the Bladder

Status Recruiting

Clinical Trial Summary

This study is for patients who have bladder cancer that invades into the muscle wall of the bladder. The standard treatment for patients with muscle invasive bladder cancer is to give 4 cycles of chemotherapy with the drugs cisplatin and gemcitabine, then to do an operation to remove the bladder (cystectomy).

In this study, the investigators will test participants' bladder cancer to see if their bladder cancer has a receptor for testosterone inside the bladder cancer cells. If it has the testosterone receptor participants will receive a medication called Degarelix that lowers testosterone levels in the blood. Degarelix will be given during the period that participants are receiving the standard of care chemotherapy drugs gemcitabine and cisplatin.

The purpose of this study is to evaluate the effects, good and bad, of adding Degarelix to standard chemotherapy for patients with bladder cancer that have the testosterone receptor.

Clinical Trial Description

Annually, over 80,000 people will be diagnosed with urothelial cell carcinoma (UCC) of the bladder in the USA, with over 17,000 deaths. For patients with muscle-invasive disease (stage II and IIIA), standard of care therapy is neoadjuvant chemotherapy followed by radical cystectomy. Neoadjuvant chemotherapy has been shown by multiple clinical trials and meta-analyses to improve pCR rates, disease free survival, and overall survival when compared to cystectomy alone. Specifically, neoadjuvant gemcitabine/cisplatin has been shown to be tolerable and effective and is a level 1 recommendation for treatment of muscle invasive bladder cancer by the National Comprehensive Cancer Network Guidelines.

The presence of a pCR in response to neoadjuvant chemotherapy is prognostic, but only about 35% of patients achieve a pCR. Thus improved neoadjuvant chemotherapy regimens are necessary to improve recurrence free survival and overall survival rates in patients with bladder cancer.

UCC is more common in men than women, with incidence rates of 3:1 to 4:1. This disparity persists even after controlling for smoking and occupational hazards/exposures and is likely influenced by androgen signaling. Androgen receptor (AR) positive UCC cells display increased proliferation, migration, and invasion in the presence of androgen and these effects are nullified in the presence of an AR antagonist. Preclinical studies show decreased rates of UCC incidence in response to a chemical carcinogen in castrated mice versus sham castrated mice and AR knockout mice versus AR intact mice. In retrospective human studies patients with UCC receiving androgen targeted therapy for concurrent prostate cancer had approximately 50% lower recurrence rates of UCC. Similarly, men receiving androgen targeted therapy for prostate cancer or benign prostatic hyperplasia have lower incidence rates of UCC than men not receiving androgen directed therapy.

Two prospective human clinical trials related to this concept have been performed. The first evaluated enzalutamide (an AR antagonist) as chemoprevention in non-muscle invasive UCC. This study was closed due to poor accrual after accruing only one patient. The second study added enzalutamide to standard chemotherapy in patients with metastatic UCC. Seven patients accrued at the therapeutic dose of enzalutamide. Overall, there was no signal for increased efficacy. However, one patient achieved a complete response lasting 2 years at last report. This patient was noted to have >90% positivity for AR in their tumor and, notably, was the only woman to participate in the study (and presumably had low testosterone levels). These data support further evaluation of androgen targeted therapy in AR+ UCC.

TASUC-neo is a pilot study conducted in patients with androgen receptor positive (AR+), pT2 - pT4, N0 - N1, M0 urothelial cell carcinoma (UCC) of the bladder. The study medication, Degarelix, will be administered concurrently with neoadjuvant gemcitabine/cisplatin. ;

Related Conditions & MeSH terms

• Androgen Receptor Positive
• Carcinoma
• Urinary Bladder Neoplasms
• Urothelial Carcinoma Bladder

• NCT number: NCT05839119
• Study type: Interventional
• Source: Brown University
• Contact: Brown University Oncology Research Group
• Phone: 401-863-3000
• Email: BrUOG@Brown.edu
• Status: Recruiting
• Phase: Phase 1
• Start date: October 2, 2023
• Completion date: January 2030