Bladder Cancer Clinical Trial
— CLONEVOOfficial 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
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)
Status | Recruiting |
Enrollment | 20 |
Est. completion date | December 2025 |
Est. primary completion date | December 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria 1. Age = 18 years old at time of informed consent 2. Histologically confirmed MIBC (T2-T4) pure or mixed histology urothelial carcinoma [urothelial carcinoma should be the dominant (>50%) histology]. 3. 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 Cockcroft-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 4. Medically fit for TURBT and radical cystectomy 5. 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 (Patients with Gilbert's syndrome with a total bilirubin =2.0 times ULN and direct bilirubin within normal limits are permitted) 6. ALT and AST = 3.0 x ULN 6. Ability to swallow oral medications 7. 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 1. 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: 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 2. 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. 3. 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. 4. 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). 5. Patients who have had major surgery within 14 days prior to Cycle 1 Day 1. 6. 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). 7. 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 8. 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. 9. Pregnant or breast-feeding women 10. 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 11. 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 12. Subjects unwilling or unable to comply with the protocol |
Country | Name | City | State |
---|---|---|---|
United States | NewYork-Presbyterian Brooklyn Methodist Hospital | Brooklyn | New York |
United States | UT Southwestern Medical Center - Simmons Comprehensive Cancer Center | Dallas | Texas |
United States | Weill Cornell Medicine | New York | New York |
United States | Moffitt Cancer Center | Tampa | Florida |
Lead Sponsor | Collaborator |
---|---|
Weill Medical College of Cornell University | Eli Lilly and Company |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Impact of Abemaciclib on clonal evolution | Clonal evolution will be assessed by whole-exome sequencing and RNA sequencing | Initiation of treatment up to 3 years | |
Primary | 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 | Incidence of Treatment-Emergent Adverse Events (TEAEs) of Abemaciclib | TEAEs will be assessed by utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. | At baseline through 3 year follow up | |
Secondary | Effect on tumor downstaging defined as <pT2 at time of cystectomy | Tumor downstaging will be assess from tissue collected at the time of cystectomy. | At baseline and post 4 week treatment |
Status | Clinical Trial | Phase | |
---|---|---|---|
Not yet recruiting |
NCT06034015 -
A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of APL-1501 Extended Release (ER) Capsules Compared to APL-1202 Immediate Release (IR) Tablets in Healthy Volunteers
|
Phase 1 | |
Recruiting |
NCT04235764 -
En-bloc Transurethral Resection of Bladder Tumor (En-bloc TURBT) Specimens Using a Redesigned Surgical Resectoscope Device
|
||
Completed |
NCT02371447 -
VPM1002BC in Recurrent Non-muscle Invasive Bladder Cancer
|
Phase 1/Phase 2 | |
Recruiting |
NCT04081246 -
Transurethral Modified En Bloc Resection For Large Bladder Tumours.
|
N/A | |
Recruiting |
NCT06059547 -
Neoadjuvant Immunotherapy in Combination With the Anti-GDF-15 Antibody Visugromab (CTL-002) for Treatment of Muscle Invasive Bladder Cancer
|
Phase 2 | |
Terminated |
NCT04779489 -
Checkpoint Inhibitor and Radiation Therapy in Bulky, Node-Positive Bladder Cancer
|
N/A | |
Not yet recruiting |
NCT04493489 -
Propranolol Adjuvant Treatment of Bladder Cancer
|
Phase 2 | |
Completed |
NCT03520231 -
Study Comparing Denosumab With Standard Treatment in Urothelial Cancer Patients With Bone Metastases
|
Phase 2 | |
Recruiting |
NCT04537221 -
Nordic Cystectomy Study III - Transfusion
|
||
Withdrawn |
NCT03007771 -
Magnetic Resonance-guided High-Intensity Focused Ultrasound (MR-HIFU) Used for Mild Hyperthermia
|
Phase 1 | |
Completed |
NCT01955408 -
Severity of Overactive Bladder Symptoms in Patients After Synergo Treatment
|
N/A | |
Completed |
NCT04487457 -
Prospective Study to Evaluate the Blood Kinetics of Immune Cells and Immunosuppressive Cytokines After Exposure to an Immunity Checkpoint Inhibitor (ICI): Study of the Impact of Chemotherapy
|
||
Active, not recruiting |
NCT04383210 -
Study of Seribantumab in Adult Patients With NRG1 Gene Fusion Positive Advanced Solid Tumors
|
Phase 2 | |
Recruiting |
NCT05562791 -
A Study of 68Gallium PSMA-PET/CT Scans in People With Bladder Cancer
|
Phase 1 | |
Completed |
NCT00199849 -
NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine
|
Phase 1 | |
Completed |
NCT02781428 -
To Detect the Sensitivity of the UroMark Assay
|
||
Recruiting |
NCT04738630 -
Study of HX008 for the Treatment of BCG-Unresponsive Non-muscle Invasive Bladder Cancer
|
Phase 2 | |
Completed |
NCT03980041 -
Study to Evaluate the Efficacy/Safety of IPI-549 in Combination With Nivolumab in Patients With Advanced Urothelial Carcinoma (MARIO-275)
|
Phase 2 | |
Active, not recruiting |
NCT03978624 -
Window of Opportunity Study of Pembrolizumab Alone and in Combinations in Bladder Cancer
|
Phase 2 | |
Completed |
NCT04534309 -
Behavioral Weight Loss Program for Cancer Survivors in Maryland
|
N/A |