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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03837821
Recruitment Status : Recruiting
First Posted : February 12, 2019
Last Update Posted : July 24, 2020
Eli Lilly and Company
Information provided by (Responsible Party):
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)

Condition or disease Intervention/treatment Phase
Bladder Cancer Drug: Abemaciclib Early Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : February 5, 2019
Estimated Primary Completion Date : February 2023
Estimated Study Completion Date : February 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Abemaciclib

Arm Intervention/treatment
Experimental: All Subjects
Abemaciclib 200 mg oral, every 12 hours
Drug: Abemaciclib
Abemaciclib 200 mg oral, every 12 hours

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

  2. 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.

Other Outcome Measures:
  1. 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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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:

    1. Creatinine clearance < 60 mL/min (by Cockgroft-Gault calculation and/or measured creatinine clearance)
    2. Hearing loss ≥ grade 2 by CTCAE criteria and/or;
    3. Neuropathy ≥ grade 2 by CTCAE criteria and/or
    4. Heart failure NYHA ≥ III
  • Medically fit for TURBT and radical cystectomy
  • Adequate organ and marrow function as defined below:

    1. Absolute neutrophil count ≥ 1.5 K/mm3
    2. White blood cell count (WBC) > 3.0 K/mm3
    3. Platelets ≥ 100 K/mm3
    4. Hemoglobin ≥ 9 g/dL
    5. Serum total bilirubin ≤ 1.5 x ULN
    6. ALT and AST ≤ 2.5 x ULN
    7. Serum creatinine clearance (CrCl) ≥ 30 ml/min using the MDRD or serum creatinine ≥ 2 times ULN using the Cockcroft-Gault or measurement with 24 hour urine collection
  • Ability to swallow oral medication
  • 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 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:

    1. Abdomen/pelvis - CT/MRI
    2. Chest - chest x-ray or CT scan
    3. 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 prior to starting study drug, or who have not recovered from the side effects of such therapy
  • 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
  • Have an active 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 months 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

Information from the National Library of Medicine

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 identifier (NCT number): NCT03837821

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Contact: GUONC Research Team 646-962-2072

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United States, New York
Weill Cornell Medicine Recruiting
New York, New York, United States, 10065
Contact: GUONC Research Team    646-962-2072   
Principal Investigator: Bishoy Faltas, M.D         
Sponsors and Collaborators
Weill Medical College of Cornell University
Eli Lilly and Company
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Principal Investigator: Bishoy Faltas, MD Weill Medical College of Cornell University
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Responsible Party: Weill Medical College of Cornell University Identifier: NCT03837821    
Other Study ID Numbers: 1710018693
First Posted: February 12, 2019    Key Record Dates
Last Update Posted: July 24, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases