Targeting Androgen Signaling in Urothelial Cell Carcinoma - Neoadjuvant

NCT05839119 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: BrUOG 428
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Urothelial Carcinoma Bladder; Androgen Receptor Positive

Keywords

UCC; Bladder Cancer; AR+

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response rate (pCR)

  Pathologic Complete Response (pCR): pCRis defined as no viable cancer cells in the resected bladder specimen.

  Cystectomy following 4 (21-Day) cycles with Gemcitabine/Cisplatin

Secondary Outcomes (4)

• Rate of non-muscle invasive disease post neoadjuvant chemotherapy (ypT0, ypTis, ypTa, ypT1)

  Cystectomy following 4 (21-Day) cycles with Gemcitabine/Cisplatin

• Relapse free survival at 2 years

  2 yrs post Cystectomy

• Relapse free survival at 5 years.

  5 yrs post Cystectomy

• AR positivity in patients with a non-pCR at cystectomy

  Cystectomy following 4 (21-Day) cycles with Gemcitabine/Cisplatin

Study Arms (1)

Treatment

EXPERIMENTAL

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. * SOC Neoadjuvant Chemotherapy: Gemcitabine/Cisplatin 21-day cycles (4 cycles total) * Gemcitabine: 1000 mg/m2 (IV) Days 1 and 8 of each cycle * Cisplatin: 70 mg/m2 (if borderline renal function: 35 mg/m2) (IV) Day 1 of each cycle (if borderline renal function, days 1 and 8 of each cycle). * Study Medication: Degarelix (SC) Every 28-days (3 cycles total) Day -7 to -2 of cycle 1, then as defined in the study calendar (approximately q28 days). "initial dose is 240 mg administered as two 120 mg (3 mL) injections (SC), followed by subsequent doses at 80 mg (4 mL) administered as one injection (SC)

Drug: Degarelix; Combination Product: Gemcitabine/Cisplatin

Interventions

Degarelix DRUG

initial dose is 240 mg administered as two 120 mg (3 mL) injections (SC), followed by subsequent doses at 80 mg (4 mL) administered as one injection (SC)

Also known as: Firmagon Kit

Treatment

Gemcitabine/Cisplatin COMBINATION_PRODUCT

SOC Neoadjuvant Chemotherapy: Gemcitabine/Cisplatin 21-day cycles (4 cycles total) * Gemcitabine: 1000 mg/m2 (IV) Days 1 and 8 of each cycle * Cisplatin: 70 mg/m2 (if borderline renal function: 35 mg/m2) (IV) Day 1 of each cycle (if borderline renal function, days 1 and 8 of each cycle).

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have the following:
• Histologically confirmed muscle invasive urothelial cell carcinoma of the bladder (pT2 - pT4)
• Eligible for standard cisplatin/gemcitabine chemotherapy as determined by the treating Medical Oncologist
• Patients must have muscle-invasive urothelial cell carcinoma of the bladder (pT2 - pT4, N0-N1, M0,) as determined by bladder biopsy or trans-urethral resection of bladder tumor (TURBT) and staging imaging studies. Patients with \<10% non-urothelial histology will remain eligible for enrollment.
• Androgen receptor positivity by IHC within the nucleus of tumor cells (as determined by study Pathologist) is required to receive study treatment.
• Patients previously treated with intravesical therapy for non-muscle invasive urothelial carcinoma of the bladder are eligible for enrollment if the agent used was not gemcitabine or a platinum-containing agent (i.e, cisplatin, carboplatin, or oxaliplatin).
• Age ≥18 years.
• Because the safety and efficacy of Degarelix in pediatric patients have not been established, children (patients \<18 years of age) are excluded from this study.
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).
• Patients must have adequate organ and marrow function as defined below:
• absolute neutrophil count ≥1,000/mcL
• platelets ≥100,000/mcL
• total bilirubin ≤ institutional upper limit of normal (ULN)
• AST(SGOT)/ALT(SGPT) ≤3 1.5 × institutional ULN
• creatinine ≤ institutional ULN OR glomerular filtration rate (GFR) ≥40 mL/min/1.73 m2

You may not qualify if:

• Patients who have previously received systemic or intravesical gemcitabine or platinum-containing chemotherapy
• Patients taking testosterone, estrogen, or other sex hormone modifying agents are excluded from this study as these medications may interfere with the activity of the study drug, Degarelix.
• Patients with uncontrolled intercurrent illness, as determined by the treating physician
• Patients who are pregnant or breastfeeding. (The effects of Degarelix on the developing human fetus are unknown. However, "based on findings in animal studies, \[Degarelix\] can cause fetal harm and loss of pregnancy when administered to a pregnant woman. In animal developmental and reproductive toxicity studies in rats and rabbits, oral administration of Degarelix during organogenesis caused embryo-fetal lethality and abortion as well as increased post-implantation loss and decreased the number of live fetuses in animals at doses less than the clinical loading dose based on body surface area." (Degarelix package insert). For this reason and the fact that other therapeutic agents used in this trial are known to be teratogenic, pregnant women are excluded from this study.

Sponsors & Collaborators

• Brown University: lead
• Legorreta Cancer Center at Brown University: collaborator
• Lifespan: collaborator
• Cures Within Reach: collaborator

Study Sites (1)

Lifespan Cancer Institute

Providence, Rhode Island, 02912, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Sheldon L Holder, MD, PhD

  Brown University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2023
• First Posted: May 3, 2023
• Study Start: October 2, 2023
• Primary Completion: July 1, 2025
• Study Completion: October 17, 2025
• Last Updated: April 2, 2026

Record last verified: 2026-03

Locations

US (1)