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

NCT03837821 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 1710018693
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

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)

Conditions

Bladder Cancer

Outcome Measures

Primary Outcomes (1)

• Change in cell-cycle dynamics between pre- and post-Abemaciclib tumor samples

  Cell-cycle dynamics will be assessed by immunohistochemistry of tumor tissues, circulating tumor DNA (ctDNA) blood samples.

  At baseline and post 4 week treatment

Secondary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events (TEAEs) of Abemaciclib

  At baseline through 3 year follow up

• Effect on tumor downstaging defined as <pT2 at time of cystectomy

  At baseline and post 4 week treatment

Other Outcomes (1)

• Impact of Abemaciclib on clonal evolution

  Initiation of treatment up to 3 years

Study Arms (1)

All Subjects

EXPERIMENTAL

Abemaciclib 200 mg oral, every 12 hours

Drug: Abemaciclib

Interventions

Abemaciclib DRUG

Abemaciclib 200 mg oral, every 12 hours

All Subjects

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years old at time of informed consent
• Histologically confirmed MIBC (T2-T4) pure or mixed histology urothelial carcinoma \[urothelial carcinoma should be the dominant (\>50%) histology\].
• Refusing cisplatin-based chemotherapy or ineligible for cisplatin-based chemotherapy due to at least one of the following:
• Creatinine clearance \< 60 mL/min (by Cockcroft-Gault calculation and/or measured creatinine clearance)
• Hearing loss ≥ grade 2 by CTCAE criteria and/or;
• Neuropathy ≥ grade 2 by CTCAE criteria and/or
• Heart failure NYHA ≥ III
• Medically fit for TURBT and radical cystectomy
• Adequate organ and marrow function as defined below:
• Absolute neutrophil count ≥ 1.5 K/mm3
• White blood cell count (WBC) \> 3.0 K/mm3
• Platelets ≥ 100 K/mm3
• Hemoglobin ≥ 9 g/dL
• Serum total bilirubin ≤ 1.5 x ULN (Patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted)
• ALT and AST ≤ 3.0 x ULN

You may not qualify if:

• Patients with locally advanced unresectable or metastatic urothelial carcinoma as assessed on baseline radiographic imaging obtained within from the date of signed consent, 28 days prior to study enrollment. Low volume (\<1.5 cm) suspicious lymph node metastases in the pelvis are allowed if they are in the LN dissection template field. The required radiographic imaging includes:
• Abdomen/pelvis - CT/MRI
• Chest - chest x-ray or CT scan
• Bone scan or FDG-PET/CT in the presence of bone pain or unexplained elevated alkaline phosphatase
• Patients with another active second malignancy other than non-melanoma skin cancers and localized prostate cancer. Patients that have completed all necessary therapy and are considered to be \<30% risk of relapse are not considered to have an active second malignancy and are eligible for enrollment.
• Patients who have received anti-cancer therapy including chemotherapy, radiotherapy, immunotherapy, and monoclonal antibodies ≤ 4 weeks or 5 half-lives, whichever is longer, prior to starting study drug. Patients who received chemotherapy must have recovered to CTCAE Grade ≤1 from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to Cycle 1 Day 1. Patients currently enrolled in any other type of medical research (for example: medical device) judged by the sponsor not to be scientifically or medically compatible with this study are also excluded.
• Patients who have serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
• Patients who have had major surgery within 14 days prior to Cycle 1 Day 1.
• Have an active bacterial infection (especially if requiring IV antibiotics), systemic fungal and/or known viral infection (for example, human immunodeficiency virus antibodies, hepatitis B surface antigen, or hepatitis C antibodies).
• Subjects who received a strong CYP3A inhibitor within 7 days prior to the first dose of study drug, or patients who require continuous treatment with a strong CYP3A inhibitor
• The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
• Pregnant or breast-feeding women
• Women who do not agree to use a medically approved contraceptive method during the treatment period and for 3 weeks following the last dose of Abemaciclib
• Men who do not agree to use a reliable method of birth control and to not donate sperm during the study and for at least 3 months following the last dose of Abemaciclib
• Subjects unwilling or unable to comply with the protocol

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Eli Lilly and Company: collaborator

Study Sites (2)

Weill Cornell Medicine

New York, New York, 10065, United States

Location

UT Southwestern Medical Center - Simmons Comprehensive Cancer Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

abemaciclib

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Bishoy Faltas, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2019
• First Posted: February 12, 2019
• Study Start: February 5, 2019
• Primary Completion: July 2, 2024
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 18, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)