- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03837821
(CLONEVO): Cell cycLe inhbitiON to Target the EVolution of UrOthelial Cancer (CLONEVO)
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
Study Overview
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Early Phase 1
Contacts and Locations
Study Contact
- Name: GUONC Research Team
- Phone Number: 646-962-2072
- Email: guonc@med.cornell.edu
Study Locations
-
-
Florida
-
Tampa, Florida, United States, 33612
- Not yet recruiting
- Moffitt Cancer Center
-
Principal Investigator:
- Roger Li, MD
-
Principal Investigator:
- Rohit Jain, MD
-
-
New York
-
Brooklyn, New York, United States, 11217
- Recruiting
- NewYork-Presbyterian Brooklyn Methodist Hospital
-
Principal Investigator:
- John Graham, MD
-
New York, New York, United States, 10065
- Recruiting
- Weill Cornell Medicine
-
Contact:
- GUONC Research Team
- Phone Number: 646-962-2072
- Email: guonc@med.cornell.edu
-
Principal Investigator:
- Bishoy Faltas, M.D
-
-
Texas
-
Dallas, Texas, United States, 75390
- Recruiting
- UT Southwestern Medical Center - Simmons Comprehensive Cancer Center
-
Contact:
- Amy Rowell
- Phone Number: 214-648-7001
- Email: mailto:Amy.Rowell@utsouthwestern.edu
-
Principal Investigator:
- Suzanne Cole, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: All Subjects
Abemaciclib 200 mg oral, every 12 hours
|
Abemaciclib 200 mg oral, every 12 hours
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in cell-cycle dynamics between pre- and post-Abemaciclib tumor samples
Time Frame: At baseline and post 4 week treatment
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Treatment-Emergent Adverse Events (TEAEs) of Abemaciclib
Time Frame: At baseline through 3 year follow up
|
TEAEs will be assessed by utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
|
At baseline through 3 year follow up
|
Effect on tumor downstaging defined as <pT2 at time of cystectomy
Time Frame: At baseline and post 4 week treatment
|
Tumor downstaging will be assess from tissue collected at the time of cystectomy.
|
At baseline and post 4 week treatment
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Impact of Abemaciclib on clonal evolution
Time Frame: Initiation of treatment up to 3 years
|
Clonal evolution will be assessed by whole-exome sequencing and RNA sequencing
|
Initiation of treatment up to 3 years
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Bishoy Faltas, MD, Weill Medical College of Cornell University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1710018693
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Bladder Cancer
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedStage III Bladder Cancer | No Evidence of Disease | Stage II Bladder Cancer | Stage IVA Bladder Cancer | Stage IVB Bladder CancerUnited States
-
H. Lee Moffitt Cancer Center and Research InstituteCompletedMuscle-Invasive Bladder Carcinoma | Bladder Cancer Stage II | Bladder Cancer Stage III | Bladder Cancer Stage IVUnited States
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)WithdrawnRecurrent Bladder Cancer | Urinary Complications | Stage 0 Bladder Cancer | Stage I Bladder Cancer | Stage II Bladder Cancer
-
Fox Chase Cancer CenterTerminatedStage III Bladder Cancer | Distal Urethral Cancer | Proximal Urethral Cancer | Squamous Cell Carcinoma of the Bladder | Urethral Cancer Associated With Invasive Bladder Cancer | Stage II Bladder CancerUnited States
-
National Cancer Institute (NCI)CompletedStage III Bladder Cancer | Stage I Bladder Cancer | Stage II Bladder CancerUnited States
-
National Cancer Institute (NCI)TerminatedStage III Bladder Cancer | Stage IV Bladder Cancer | Recurrent Bladder Carcinoma | Bladder Adenocarcinoma | Bladder Squamous Cell Carcinoma | Bladder Urothelial Carcinoma | Stage I Bladder Cancer | Stage II Bladder CancerUnited States
-
University of WashingtonNational Cancer Institute (NCI)CompletedStage III Bladder Cancer | Stage IV Bladder Cancer | Recurrent Bladder Carcinoma | Stage II Bladder CancerUnited States
-
Academisch Medisch Centrum - Universiteit van Amsterdam...Bristol-Myers SquibbRecruitingUrinary Bladder Cancer | Invasive Bladder CancerNetherlands
-
Taris Biomedical LLCBristol-Myers SquibbTerminatedBladder Cancer TNM Staging Primary Tumor (T) T2 | Bladder Cancer TNM Staging Primary Tumor (T) T2A | Bladder Cancer TNM Staging Primary Tumor (T) T2B | Bladder Cancer TNM Staging Primary Tumor (T) T3 | Bladder Cancer TNM Staging Primary Tumor (T) T3A | Bladder Cancer TNM Staging Primary Tumor... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Bladder Cancer | Stage III Bladder Cancer | Stage IV Bladder Cancer | Transitional Cell Carcinoma of the Bladder | Stage I Bladder Cancer | Stage II Bladder CancerUnited States
Clinical Trials on Abemaciclib
-
Nader SanaiEli Lilly and Company; Barrow Neurological Institute; Ivy Brain Tumor CenterNot yet recruiting
-
University of ArizonaGeorge Washington UniversityRecruiting
-
Memorial Sloan Kettering Cancer CenterEli Lilly and CompanyActive, not recruiting
-
Gustave Roussy, Cancer Campus, Grand ParisCompleted
-
Medical College of WisconsinRecruitingSoft Tissue Sarcoma | Osteosarcoma | ChondrosarcomaUnited States
-
Eli Lilly and CompanyCompletedHealthyUnited States
-
Eli Lilly and CompanyCompleted
-
Memorial Sloan Kettering Cancer CenterEli Lilly and Company; Incyte CorporationRecruitingMyelofibrosis Due to and Following Polycythemia VeraUnited States
-
Nader SanaiEli Lilly and Company; Barrow Neurological Institute; Ivy Brain Tumor CenterRecruitingGlioma | Glioblastoma | GBMUnited States
-
Case Comprehensive Cancer CenterRecruitingSmall-cell Lung Cancer | Large Cell Neuroendocrine Carcinoma of the Lung | Extrapulmonary Small Cell CarcinomaUnited States