Cabozantinib in Combination With Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Cancer
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|ClinicalTrials.gov Identifier: NCT04878029|
Recruitment Status : Recruiting
First Posted : May 7, 2021
Last Update Posted : August 10, 2022
|Condition or disease||Intervention/treatment||Phase|
|Infiltrating Bladder Urothelial Carcinoma With Squamous Differentiation Locally Advanced Urothelial Carcinoma Metastatic Urothelial Carcinoma Unresectable Urothelial Carcinoma||Drug: Cabozantinib S-malate Drug: Enfortumab Vedotin Other: Quality-of-Life Assessment Other: Questionnaire Administration||Phase 1|
I. To determine the recommended phase II dose (RP2D) of cabozantinib s-malate (cabozantinib) and enfortumab vedotin 1.25 mg/kg on days 1, 8 and 15 of a 28-day cycle based on safety and tolerability. (Phase I dose escalation) II. To evaluate the ongoing safety and tolerability of cabozantinib and enfortumab vedotin in a dose expansion cohort. (Phase Ib dose expansion)
I. Obtain preliminary evidence of anti-tumor activity of the combination of cabozantinib and enfortumab vedotin by assessing the objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1.
II. Progression-free survival (PFS). III. Overall survival (OS). IV. Disease control rate by RECIST v1.1.
I. To assess the pharmacokinetic (PK) profile of cabozantinib during treatment with enfortumab vedotin.
II. To evaluate the effect of the combination on selected biomarkers in the tumor microenvironment, systemic circulation and gut microbiome and their relationship with efficacy of the combination.
III. To evaluate quality of life, frailty and sarcopenia before, during and at the time of treatment completion.
OUTLINE: This is dose-escalation study of cabozantinib.
Patients receive cabozantinib orally (PO) once daily (QD) on days 1-28 and enfortumab vedotin intravenously (IV) on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 12 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/Ib Open Label, Single-Arm Study of Cabozantinib in Combination With Enfortumab Vedotin (EV) in the Treatment of Locally Advanced or Metastatic Urothelial Cancer|
|Actual Study Start Date :||July 23, 2021|
|Estimated Primary Completion Date :||January 21, 2025|
|Estimated Study Completion Date :||January 21, 2025|
Experimental: Treatment (cabozantinib, enfortumab vedotin)
Patients receive cabozantinib PO QD on days 1-28 and enfortumab vedotin IV on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Cabozantinib S-malate
Drug: Enfortumab Vedotin
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
Other: Questionnaire Administration
- Incidence of adverse events [ Time Frame: Up to study completion (estimated 5 years) ]Will be assessed by the Common Terminology Criteria for Adverse Events version 5.0.
- Objective response rate [ Time Frame: Through study completion, an average of 1 year ]Based on cross-sectional imaging. Categorized according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. ORR will be summarized with the 2-sided 95% confidence interval (CI) using the Clopper-Pearson method in the full analysis set (FAS).
- Progression-free survival [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months. ]Kaplan-Meier methods will be used to estimate median survival time or time-specific survival rate with 95% confidence interval.
- Overall survival [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months. ]Kaplan-Meier methods will be used to estimate median survival time or time-specific survival rate with 95% confidence interval.
- Disease control rate (DCR) [ Time Frame: Up to study completion (estimated 5 years) ]Defined as the percentage of patients who achieve complete response, partial response and stable disease as per RECIST v1.1. DCR will be summarized with the 2-sided 95% CI using the Clopper-Pearson method in the FAS.
- Maximum Plasma Concentration [Cmax] [ Time Frame: Up to study completion (estimated 5 years) ]Pharmacokinetic of cabozantinib during treatment with enfortumab vedotin will be analyzed
- Biomarker analysis [ Time Frame: Up to study completion (estimated 5 years) ]Tumor tissue from pre-enrollment biopsy and correlative peripheral blood samples collected at baseline, on days 1, 8 and 15 during cycle 1 and day 1 of cycle 2 will be assessed for molecular biomarkers not limited to Nectin-4, MET and PDL1. Stool samples will be collected at baseline, during Cycle 3 and at the Off-Treatment Visit to assess for changes in intestinal flora over the course of treatment.
- Quality of life assessment [ Time Frame: Through study completion, an average of 1 year ]Functional Assessment of Cancer Therapy - Bladder Cancer questionnaire will be filled out at baseline and every 8 weeks (+/- 7 days) during year 1 of treatment
- Frailty assessment [ Time Frame: Through study completion, an average of 1 year ]Fried Frailty assessment will be obtained at baseline and every 8 weeks (+/- 7 days) during year 1 of treatment.
- Sarcopenia assessment [ Time Frame: Through study completion, an average of 1 year ]SliceOmatic v5.0 by TomoVision will be used to measure change in muscle/adipose tissue on imaging studies obtained.
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): NCT04878029
|Contact: Mehmet Bilen, MDemail@example.com|
|United States, Georgia|
|Emory University Hospital/Winship Cancer Institute||Recruiting|
|Atlanta, Georgia, United States, 30322|
|Contact: Wilena A. Session 404-778-3448 firstname.lastname@example.org|
|Principal Investigator: Mehmet A. Bilen, MD|
|Principal Investigator:||Mehmet A Bilen, MD||Emory University Hospital/Winship Cancer Institute|