RECRUITING

Targeting Androgen Signaling in Urothelial Cell Carcinoma - Neoadjuvant

Conditions

Urothelial Carcinoma Bladder Androgen Receptor Positive UCC Bladder Cancer AR+

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2023-10-02

Study Completion:2030-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05839119

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
3.1.1 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 3.1.2 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. 3.1.3 Androgen receptor positivity by IHC within the nucleus of tumor cells (as determined by study Pathologist) is required to receive study treatment. 3.1.4 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). 3.1.5 Age ≥18 years. 3.1.6 ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A). 3.1.7 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 3.1.8 Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. 3.1.9 For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. 3.1.10 Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. 3.1.11 Patients with metastases, including treated brain metastases, are not eligible for enrollment. 3.1.12 Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen, and prior therapy did not include gemcitabine or a platinum-containing agent, are eligible for this trial. 3.1.13 Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better. 3.1.14 For women of childbearing potential, a negative serum pregnancy test within 7 days prior to registration 3.1.15 Women of childbearing potential and male participants must practice highly effective form of non-hormonal contraception throughout the study, which is defined as from study screening (ICF) through at least six months post last treatment. It must be documented this was discussed with the patient. 3.1.16 Ability to understand and the willingness to sign a written informed consent document.	3.2.1 Patients who have previously received systemic or intravesical gemcitabine or platinum-containing chemotherapy 3.2.2 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. 3.2.3 Patients with uncontrolled intercurrent illness, as determined by the treating physician 3.2.4 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.

Inclusion Criteria

Exclusion Criteria

3.1.1 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
3.1.2 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.
3.1.3 Androgen receptor positivity by IHC within the nucleus of tumor cells (as determined by study Pathologist) is required to receive study treatment.
3.1.4 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).
3.1.5 Age ≥18 years.
3.1.6 ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).
3.1.7 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
3.1.8 Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
3.1.9 For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
3.1.10 Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
3.1.11 Patients with metastases, including treated brain metastases, are not eligible for enrollment.
3.1.12 Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen, and prior therapy did not include gemcitabine or a platinum-containing agent, are eligible for this trial.
3.1.13 Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
3.1.14 For women of childbearing potential, a negative serum pregnancy test within 7 days prior to registration
3.1.15 Women of childbearing potential and male participants must practice highly effective form of non-hormonal contraception throughout the study, which is defined as from study screening (ICF) through at least six months post last treatment. It must be documented this was discussed with the patient.
3.1.16 Ability to understand and the willingness to sign a written informed consent document.

3.2.1 Patients who have previously received systemic or intravesical gemcitabine or platinum-containing chemotherapy
3.2.2 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.
3.2.3 Patients with uncontrolled intercurrent illness, as determined by the treating physician
3.2.4 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.

Contacts and Locations

Study Contact

Brown University Oncology Research Group

CONTACT

401-863-3000

BrUOG@Brown.edu

Principal Investigator

Sheldon L Holder, MD, PhD

PRINCIPAL_INVESTIGATOR

Brown University

Study Locations (Sites)

Lifespan Cancer Institute

Providence, Rhode Island, 02912

United States

Collaborators and Investigators

Sponsor: Brown University

Sheldon L Holder, MD, PhD, PRINCIPAL_INVESTIGATOR, Brown University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-10-02

Study Completion Date2030-01

Study Record Updates

Study Start Date2023-10-02

Study Completion Date2030-01

Terms related to this study

Keywords Provided by Researchers

UCC
Bladder Cancer
AR+

Additional Relevant MeSH Terms

Urothelial Carcinoma Bladder
Androgen Receptor Positive