Protocol: 23-1008 / IRB23-1008
Phase: II
Investigator: Pooja Ghatalia, MD
Disease(s): Other Urinary and Urinary Bladder
Full Title: GU-217: A Pilot Trial of Enfortumab Vedotin Schedule De-escalation in Metastatic Urothelial Carcinoma

Study Summary

The purpose of this research study is to investigate an alternative dosing schedule for the drug enfortumab vedotin (EV). Enfortumab vedotin is a drug with FDA approval for metastatic urothelial cancer. EV is a highly active drug in treating metastatic urothelial cancer. It is also being studied in combination with pembrolizumab in several clinical trials. However, the drug has a high risk of side effects. Almost half of patients develop severe or life-threatening significant side effects related to EV. Some of the common side effects with EV are peripheral neuropathy (numbness and tingling in toes and fingers), rashes, itching, fatigue and diarrhea. On clinical trials using EV, about one-half of the patients needed to hold the medication and about 1/3rd needed to reduce the dose of the medication.

In this study our goal is to examine an alternate way of administering EV with the goal of reducing the side effects while maintaining remaining on treatment for a longer period of time. The plan is to start treating with EV at the standard schedule initially and then slowly reduce the frequency of administering EV in patients with good cancer control.

We do not know if you will benefit from this research study. The alternative dosing schedule of enfortumab vedotin with or without pembrolizumab is with the goal of improving your ability to tolerate the treatment. However, it may lead to same or worse outcomes compared to standard schedule with no additional benefit compared to standard treatment. We can use what we learn from this research study to help other people with the same disease.

Approximately 70 patients will take part in this multicenter study.

Before you begin the study, you will need to have certain exams, tests or procedures to find out if you can be in the research study. These exams, tests or procedures are part of regular cancer care and may be done even if you do not join the research study. If you have had some of them recently, they may not need to be repeated. This will be up to your study doctor.

If the screening procedures show you can take part in the study and you decide to take part in the study, you will be enrolled to receive either enfortumab vedotin alone (Main Arm) or enfortumab vedotin and pembrolizumab (Exploratory Arm). There is no placebo used in this trial. Whether you receive enfortumab vedotin alone or in combination with pembrolizumab will be determined by your treating physician.

These are standard FDA approved medications and so they will be available to you as part of standard of care. The medications are administered intravenously. The schedule of administration will be adjusted based on the response you achieve while on study. Your treating physician may change your dosage during the study based on how you are doing and/or any side effects that you experience.

If you are in the part of the study where you receive enfortumab vedotin alone, you will start treatment once weekly for three weeks followed by one week “off” of each 28-day cycle at the standard schedule. As part of this study, if you have good disease control, then as part of this study, your treatment schedule will be adjusted. If the adjusted schedule does not control your cancer optimally then you will go back to the standard dosing schedule of enfortumab vedotin.

If you are in the part of the study where you receive enfortumab vedotin with pembrolizumab, you will be treated with enfortumab vedotin during the first and second week of every 3-week (or 21-day) cycle and pembrolizumab is dosed on day 1 every 21-days. As part of this study, if you have good disease control at 18 weeks, then enfortumab vedotin frequency will be reduced and pembrolizumab is continued. If the adjusted schedule does not control your cancer optimally then you will go back to the standard dosing schedule of enfortumab vedotin.

Eligibility

To be eligible for this study, patients must meet several criteria, including but not limited to the following:

• Patients must be 18 years or older
• Patients must have histologically and radiographically confirmed locally advanced or metastatic urothelial carcinoma
• Patients must be planned to receive EV as standard treatment for advanced urothelial cancer
• Patients must not have grade 2 or higher baseline sensory or motor neuropathy.
• Patients must not have uncontrolled diabetes defined as HbA1c > 8%

ClinicalTrials.gov

Visit ClinicalTrials.gov for a full clinical trial description