Actively Recruiting
A Phase I/Ib Study of Cabozantinib and Enfortumab Vedotin in Locally Advanced or Metastatic Urothelial Cancer
Led by Emory University · Updated on 2026-04-29
32
Participants Needed
1
Research Sites
57 weeks
Total Duration
On this page
Sponsors
E
Emory University
Lead Sponsor
E
Exelixis
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are studying a combination of two drugs, cabozantinib and enfortumab vedotin, in adults with locally advanced or metastatic urothelial cancer, which is a type of bladder cancer that has spread to nearby tissues, lymph nodes, or other parts of the body. This phase I/Ib trial aims to find the best dose, assess possible benefits, and monitor side effects of this drug combination. Cabozantinib works by blocking enzymes needed for tumor cell growth, while enfortumab vedotin targets tumor cells specifically to deliver a toxic agent that kills them. In this study, patients take cabozantinib by mouth once daily during a 28-day cycle and receive enfortumab vedotin intravenously on days 1, 8, and 15 of each cycle. The cycles repeat every 28 days as long as the disease does not progress or side effects remain acceptable. The study includes a dose-escalation phase to find the recommended dose and a dose-expansion phase to further evaluate safety and tolerability. Participants will be closely monitored throughout the study with follow-up visits 30 days after treatment ends and then every 12 weeks. Researchers will assess side effects, tumor response using standardized criteria, progression-free survival, overall survival, and quality of life. They will also study drug effects on biomarkers and the gut microbiome. The study is expected to last up to five years for safety evaluations.
CONDITIONS
Brief Title
Cabozantinib in Combination With Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Histologically confirmed urothelial carcinoma, including squamous or mixed cell types
- Metastatic or unresectable locally advanced disease
- Prior treatment with a checkpoint inhibitor (PD-1 or PD-L1 inhibitor)
- Prior platinum-containing chemotherapy or ineligible for it at enrollment
- Recovery to baseline or Grade 1 or less side effects from prior treatments
- Available tumor tissue samples or willingness for repeat biopsy
- Measurable disease per RECIST 1.1
- ECOG performance status of 0, 1, or 2
- Age 18 years or older
- Adequate blood counts and organ function within 28 days before treatment
- Ability to understand and comply with protocol and provide consent
- Agreement to use contraception during and 4 months after treatment
- Female participants of childbearing potential must not be pregnant
You will not qualify if you...
- Prior treatment with cabozantinib
- Prior enfortumab vedotin study participation or MMAE-based ADCs
- Recent kinase inhibitor or systemic anticancer therapy within 2 weeks
- Radiation therapy within 2 weeks or systemic radionuclide within 6 weeks
- Known untreated or unstable brain metastases
- Use of certain anticoagulants not allowed or unstable doses
- Uncontrolled cardiovascular disorders or recent serious heart events
- Gastrointestinal disorders with risk of perforation or fistula
- Significant bleeding within 12 weeks before treatment
- Cavitating pulmonary lesions or major blood vessel involvement
- Ongoing sensory or motor neuropathy grade 2 or higher
- Other significant disorders precluding safe participation
- Recent major or minor surgery without complete healing
- Corrected QT interval > 500 ms on ECG
- Pregnancy or lactation
- Inability to swallow tablets
- Allergy to study treatments
- Other active cancers requiring treatment within 3 years except certain cured cancers
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Repeated 28-day cycles until disease progression or discontinuation
Participants receive cabozantinib orally once daily on days 1-28 and enfortumab vedotin intravenously on days 1, 8, and 15 of each 28-day cycle. Treatment continues in repeated 28-day cycles until disease progression or unacceptable side effects occur.
Visits on days 1, 8, and 15 of each cycle for IV treatment and daily oral medication
Duration - Up to 5 years
After completing treatment, participants are followed up to monitor safety and health status.
1 visit at 30 days post-treatment and then visits every 12 weeks
Trial Site Locations
Total: 1 location
1
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States, 30322
Actively Recruiting
Research Team
M
Mehmet Bilen, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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