Status:
ACTIVE_NOT_RECRUITING
(CLONEVO): Cell cycLe inhbitiON to Target the EVolution of UrOthelial Cancer
Lead Sponsor:
Weill Medical College of Cornell University
Collaborating Sponsors:
Eli Lilly and Company
Conditions:
Bladder Cancer
Eligibility:
All Genders
18+ years
Phase:
EARLY_PHASE1
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-A...
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 an...
Eligibility Criteria
Inclusion
- Inclusion Criteria
- 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
- Ability to swallow oral medications
- Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and randomization
- Exclusion Criteria
- 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
Exclusion
Key Trial Info
Start Date :
February 5 2019
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
December 1 2026
Estimated Enrollment :
20 Patients enrolled
Trial Details
Trial ID
NCT03837821
Start Date
February 5 2019
End Date
December 1 2026
Last Update
November 18 2025
Active Locations (2)
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1
Weill Cornell Medicine
New York, New York, United States, 10065
2
UT Southwestern Medical Center - Simmons Comprehensive Cancer Center
Dallas, Texas, United States, 75390