Renal Retention in High Grade Upper Tract Urothelial Cancer
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|ClinicalTrials.gov Identifier: NCT05656235|
Recruitment Status : Not yet recruiting
First Posted : December 19, 2022
Last Update Posted : January 9, 2023
|Condition or disease||Intervention/treatment||Phase|
|High Grade Urothelial Carcinoma Bladder Cancer Urothelial Carcinoma Bladder||Drug: Enfortumab vedotin Drug: Pembrolizumab||Phase 2|
This single arm phase II trial will evaluate the use of enfortumab vedotin and pembrolozumab for high grade upper tract urothelial cancer patients who are unable or unwilling to undergo standard of care nephroureterectomy.
Enfortumab vedotin IV 1.25 mg/kg days 1,8 and pembrolizumab 200 mg IV will be delivered every 21 days in 20 patients with high grade UTUC cT2-T4N0 (non-metastatic) until disease progression outside of the renal/ureter unit and/or intolerance.
Primary objective is event free survival (EFS), defined as the time to systemic relapse or death. The hypothesis is that the combination of pembrolizumab and enfortumab vedotin for patients with high grade non-metastatic UTUC deferring nephroureterectomy will lead to EFS outcomes similar to that achieved by RNU in historical dataset from the Brady Urologic Institute database (based on a subset of 85 patients with high grade UTUC cT2-T4N0 who underwent surgery without perioperative chemotherapy).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Renal Retention in High Grade Upper Tract Urothelial Cancer: A Phase II Trial of Enfortumab Vedotin and Pembrolizumab in Patients With Upper Tract Urothelial Cancer (UTUC) Who Are Not Candidates for, or Refuse, Nephroureterectomy|
|Estimated Study Start Date :||February 2023|
|Estimated Primary Completion Date :||March 2026|
|Estimated Study Completion Date :||March 2027|
Experimental: Enfortumab vedotin with Pembrolizumab
The study population will include male and female patients over the age of 18 with high grade UTUC (cN0/xM0) and is ineligible for or refuses definitive radical nephroureterectomy (RNU).
Enfortumab vedotin will be administered on Days 1 and 8 at 1.25mg/kg of every 3-week cycle by intravenous (IV) infusion given over approximately 30 minutes. Pembrolizumab will be administered on Day 1 at 200mg of every 3-week cycle by IV infusion over approximately 30 minutes. Enfortumab vedotin and Pembrolizumab may be administered for up to total of 35 cycles (approximately 2 years).
Drug: Enfortumab vedotin
Enfortumab vedotin 1.25mg/kg on Days 1 and 8 every 3 weeks for up to 35 weeks (each cycle = 21 days)
Other Name: Padcev
Pembrolizumab 200mg on Day 1 every 3 weeks for up to 35 weeks (each cycle = 21 days)
Other Name: Keytruda
- Event free survival (EFS) [ Time Frame: 12 months ]Time to relapse or death based on 12 months.
- Glomerular Filtration Rate (GFR) [ Time Frame: Baseline, 12 months ]Change from baseline GFR to GFR 1 yr post enrollment
- To evaluate safety and tolerability of the combination of enfortumab vedotin and pembrolizumab [ Time Frame: 25 months ]Number of participants experiencing dose limiting toxicities and treatment-related adverse events, as defined by Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0).
- Progression free survival [ Time Frame: 48 months ]Number of participants without disease recurrence
- Overall Survival [ Time Frame: 48 months ]Number of participants alive end of trial.
- To assess feasibility of obtaining tumor for DNA sequencing including, FGFR mutation / fusion status, from UTUC biopsy specimens [ Time Frame: 24 months ]Number participants with tumor available for DNA sequencing including, FGFR mutation / fusion status, from UTUC biopsy specimens
- To assess feasibility of obtaining immune biomarker data from UTUC biopsy specimens [ Time Frame: 24 months ]Number of participants with immune biomarker data available from UTUC biopsy specimens
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05656235
|Contact: Tanya O'Neal, RNfirstname.lastname@example.org|
|United States, District of Columbia|
|Johns Hopkins University: Sibley Memorial Hospital|
|Washington, District of Columbia, United States, 20016|
|Contact: Carol Goldener, RN 202-660-5629 email@example.com|
|Principal Investigator: Jean Hoffman-Censits, MD|
|United States, Maryland|
|Johns Hopkins University: Sidney Kimmel Comprehensive Cancer Center|
|Baltimore, Maryland, United States, 21287|
|Contact: Tanya O'Neal, RN 410-955-9797 firstname.lastname@example.org|
|Principal Investigator: Jean Hoffman-Censtis, MD|
|Principal Investigator:||Jean Hoffman-Censits, MD||Johns Hopkins University|