(CLONEVO): Cell cycLe inhbitiON to Target the EVolution of UrOthelial Cancer

Early Phase 1

Active, not recruiting

• Conditions: Bladder Cancer
• Interventions: Drug: Abemaciclib

• Registration Number: NCT03837821
• Lead Sponsor: Weill Medical College of Cornell University

Brief Summary

Single-arm, open-label window-of-opportunity trial of neoadjuvant Abemaciclib in 20 patients, with tumor tissue obtained as standard of care at tumor resection (pre-Abemaciclib) and cystectomy (post-Abemaciclib)

Detailed Description

A Window-of-Opportunity Trial of Abemaciclib followed by radical cystectomy in patients with Platinum-Ineligible Urothelial Carcinoma to Evaluate CDK4/6-Dependent Phosphorylation of Pocket Proteins and Clonal Evolution Dynamics. Subjects will be treated with Abemaciclib at 200 mg every 12 hours for at least 4 weeks (and likely slightly longer depending upon surgical date). Individual dose reductions will be made on the basis of the AEs observed. In the absence of treatment delays due to adverse event(s), treatment will be continued until the surgical date unless any of the following criteria applies: 1-Disease progression; 2-Intercurrent illness that prevents further administration of treatment; 3-Unacceptable adverse event(s) as a result of Abemaciclib; 4- Patient decides to withdraw from the study; 5-General or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator. Patients will be followed with history, physical, and blood tests at each visit to monitor for toxicity. Patients will be followed for survival endpoints following completion of this study for 3 years after surgery or until death. Patients removed from study for unacceptable adverse events will be followed until resolution or stabilization of the adverse event.

Study Timeline

• Study Start: 2019-02-05
• Study First Submitted: 2019-02-06
• Study First Submitted QC: 2019-02-08
• Study First Posted: 2019-02-12
• Primary Completion: 2024-07-02
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-18
• Last Update Posted: 2024-12-24
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
All Subjects	Abemaciclib	Abemaciclib 200 mg oral, every 12 hours

Primary Outcome Measures

Name	Time	Method
Change in cell-cycle dynamics between pre- and post-Abemaciclib tumor samples	At baseline and post 4 week treatment	Cell-cycle dynamics will be assessed by immunohistochemistry of tumor tissues, circulating tumor DNA (ctDNA) blood samples.

Secondary Outcome Measures

Name	Time	Method
Effect on tumor downstaging defined as <pT2 at time of cystectomy	At baseline and post 4 week treatment	Tumor downstaging will be assess from tissue collected at the time of cystectomy.
Incidence of Treatment-Emergent Adverse Events (TEAEs) of Abemaciclib	At baseline through 3 year follow up	TEAEs will be assessed by utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Trial Locations

Locations (4)

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

NewYork-Presbyterian Brooklyn Methodist Hospital; 🇺🇸 Brooklyn, New York, United States

Weill Cornell Medicine; 🇺🇸 New York, New York, United States

UT Southwestern Medical Center - Simmons Comprehensive Cancer Center; 🇺🇸 Dallas, Texas, United States