Abemaciclib for Bladder Cancer

(CLONEVO Trial)

Not currently recruiting at 3 trial locations

Overseen By GUONC Research Team

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Weill Medical College of Cornell University

Must not be taking: Strong CYP3A inhibitors

Disqualifiers: Metastatic cancer, Second malignancy, Infections, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for bladder cancer using the drug Abemaciclib. The goal is to assess its effect on tumors before surgery. It targets individuals with muscle-invasive bladder cancer who cannot or choose not to undergo standard chemotherapy. Eligible participants must have a diagnosis of muscle-involved bladder cancer and be medically fit for surgery. This trial provides an opportunity to explore a new approach to treating bladder cancer. As an Early Phase 1 trial, the research focuses on understanding how the treatment works in people, allowing participants to be among the first to receive it.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot take strong CYP3A inhibitors within 7 days before starting the study drug, and you should not require continuous treatment with them during the trial.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot take strong CYP3A inhibitors within 7 days before starting the study drug. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that Abemaciclib is likely to be safe for humans?

Research has shown that Abemaciclib, the treatment tested in this trial, has promising safety results from earlier studies. For example, one study found it was well-tolerated when given before surgery to patients with muscle-invasive bladder cancer. This indicates that while the drug targets cancer cells, it usually doesn't cause severe side effects for most people.

However, Abemaciclib remains in early testing stages for bladder cancer, so researchers continue to collect safety information. If there are any concerns, discussing them with the trial team or a doctor is advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for bladder cancer, which often include chemotherapy or immunotherapy, Abemaciclib offers a unique approach by targeting specific enzymes called CDK4 and CDK6. These enzymes are crucial for cell division, and by inhibiting them, Abemaciclib can potentially stop cancer cells from multiplying. Researchers are excited about this treatment because it represents a more targeted approach, potentially leading to fewer side effects and better outcomes for patients. Additionally, its oral administration makes it more convenient compared to some traditional therapies that require intravenous delivery.

What evidence suggests that Abemaciclib might be an effective treatment for bladder cancer?

Research has shown that Abemaciclib may help treat bladder cancer. One study found that patients who took Abemaciclib before surgery experienced a 31% reduction in tumor size, indicating significant shrinkage. This is promising because smaller tumors are often easier to treat. Abemaciclib blocks specific proteins, particularly CDK4/6, that aid cancer cell growth. Although more research is necessary, these early results suggest that Abemaciclib could effectively combat bladder cancer. Participants in this trial will receive Abemaciclib 200 mg orally every 12 hours to further evaluate its effectiveness. ^{1 2 5 6 7}

Who Is on the Research Team?

Bishoy Faltas, MD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with muscle-invasive bladder cancer (MIBC) stages T2-T4, who can't or won't use cisplatin-based chemo. They must be fit for surgery, not have had recent major surgery or anti-cancer therapy, and agree to contraception if applicable.

Inclusion Criteria

My blood tests, liver function, and ability to take pills are all within normal ranges.

I finished radiotherapy at least 14 days ago and have recovered from its immediate effects.

My bladder cancer is mostly urothelial and confirmed by tissue analysis.

Exclusion Criteria

I agree to use birth control as advised by my doctor.

I do not have serious or uncontrolled health conditions.

Subjects unwilling or unable to comply with the protocol

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Abemaciclib at 200 mg every 12 hours for at least 4 weeks

4 weeks

Regular visits for monitoring toxicity and dose adjustments

Surgery

Radical cystectomy is performed after the treatment phase

1 week

1 visit (in-person) for surgery

Follow-up

Participants are monitored for survival endpoints and adverse events for 3 years after surgery

3 years

Periodic visits for history, physical, and blood tests

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib

Trial Overview The trial tests Abemaciclib as a neoadjuvant treatment in bladder cancer patients. It's a single-arm study where all participants receive the drug before their tumors are surgically removed, allowing comparison of tissue samples before and after treatment.

How Is the Trial Designed?

Group I: All Subjects Experimental Treatment 1 Intervention

Abemaciclib 200 mg oral, every 12 hours

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

Dovitinib was administered to 13 patients with treatment-resistant non-muscle-invasive urothelial carcinoma, achieving biologically active concentrations in urothelial tissue but only an 8% complete response rate, indicating limited clinical efficacy.

Despite showing pharmacodynamic activity by reducing pFGFR3 levels, the high frequency of severe toxicity (grade 3-4 events in all patients) led to the conclusion that long-term use of dovitinib is not feasible, and patient selection based solely on pFGFR3 expression may not effectively predict treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Trial of Dovitinib in BCG-Unresponsive Urothelial Carcinoma with FGFR3 Mutations or Overexpression: Hoosier Cancer Research Network Trial HCRN 12-157. Hahn, NM., Bivalacqua, TJ., Ross, AE., et al.[2019]

Neoadjuvant chemotherapy has been shown to improve overall survival in patients with locally advanced muscle-invasive bladder cancer, but its use in clinical practice remains low due to ongoing controversies regarding adjuvant chemotherapy.

Recent advancements include the approval of atezolizumab, a checkpoint inhibitor, for metastatic bladder cancer, alongside other promising therapies targeting mutational signatures, such as VEGF and HER2-directed agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic therapy in muscle-invasive and metastatic bladder cancer: current trends and future promises. Aragon-Ching, JB., Trump, DL.[2017]

In a study of 114 BCG-unresponsive non-muscle-invasive bladder cancer patients with a median follow-up of 71.2 months, bladder-sparing treatment (BST) showed similar long-term overall survival and cancer-specific survival rates compared to early radical cystectomy (RC).

BST resulted in a high-grade recurrence-free rate of 37% and an 83% rate of progression-free survival from muscle-invasive disease, suggesting it may be a safe option for selected patients, particularly non-smokers and those without lymphovascular invasion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bladder-sparing Treatment in Patients with Bacillus Calmette-Guerin-unresponsive Non-muscle-invasive Bladder Cancer: An Analysis of Long-term Survival Outcomes. Tan, WS., Grajales, V., Contieri, R., et al.[2023]

Urothelial carcinoma, the most common urological cancer, is primarily treated with Bacillus Calmette-Guerin (BCG) immunotherapy for superficial cases and cisplatin-based chemotherapy for metastatic disease, with vinflunine as the standard second-line option in Europe.

Novel PD-1/PD-L1 inhibitors like atezolizumab, nivolumab, and pembrolizumab have shown promise in treating bladder cancer, particularly for patients who cannot tolerate cisplatin, and are generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy for Bladder Cancer]. Büchler, T.[2019]

In the BC2001 trial involving 458 patients with muscle-invasive bladder cancer, the addition of chemotherapy (5-fluorouracil and mitomycin C) to radiotherapy led to significant improvements in local control and bladder cancer-specific survival.

While patients experienced a decline in health-related quality of life (HRQoL) immediately after treatment, their quality of life returned to baseline levels within 6 months, and the addition of chemotherapy did not negatively impact long-term HRQoL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported Quality of Life Outcomes in Patients Treated for Muscle-invasive Bladder Cancer with Radiotherapy ± Chemotherapy in the BC2001 Phase III Randomised Controlled Trial. Huddart, RA., Hall, E., Lewis, R., et al.[2021]

Recent advances in bladder cancer research have identified key molecular pathways and driver genes that differentiate low-grade from high-grade tumors, which can help in personalizing treatment strategies for patients.

The use of urine as a non-invasive liquid biopsy for bladder cancer is promising, potentially allowing for better monitoring of recurrence and reducing the need for invasive procedures like cystoscopies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular Oncology of Bladder Cancer from Inception to Modern Perspective. Lokeshwar, SD., Lopez, M., Sarcan, S., et al.[2023]

Cisplatin and gemcitabine are the most commonly used first-line treatment for advanced bladder cancer, showing comparable efficacy and better tolerance than the traditional four-drug regimen, especially for patients who cannot receive cisplatin due to comorbidities.

Recent advancements in molecular characterization of advanced bladder cancer have revealed actionable genetic alterations, leading to the development of targeted therapies that may significantly improve treatment outcomes by matching specific mutations with appropriate treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of genomics in the management of advanced bladder cancer. Guancial, EA., Rosenberg, JE.[2018]

In a study of 44 patients with muscle-invasive bladder cancer (MIBC), the combination of neoadjuvant gemcitabine and cisplatin with atezolizumab resulted in 69% of patients achieving non-muscle-invasive downstaging, indicating a promising efficacy for this treatment regimen.

The most common serious side effect was neutropenia, affecting 36% of patients, but no patients were unable to undergo surgery due to adverse events, suggesting that the treatment is relatively safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Atezolizumab With Gemcitabine and Cisplatin in Patients With Muscle-Invasive Bladder Cancer: A Multicenter, Single-Arm, Phase II Trial. Funt, SA., Lattanzi, M., Whiting, K., et al.[2023]

Intravesical gemcitabine showed a high complete response rate of 84.8% at 3 months in patients with intermediate and high-risk non-muscle invasive bladder cancer (NMIBC), indicating its efficacy as a first-line adjuvant therapy during BCG shortages.

The treatment was well-tolerated, with 78.8% of patients completing the full induction therapy, and common side effects included dysuria and fatigue, suggesting a favorable safety profile for short-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine as first-line therapy for high-grade non-muscle invasive bladder cancer: results from a tertiary center in the contemporary BCG-shortage era. Zeng, J., Funk, J., Lee, BR., et al.[2023]

In a study of 64 patients with high-risk superficial bladder cancer, bacillus Calmette-Guérin (BCG) treatment resulted in a significantly lower recurrence rate (28.1%) compared to gemcitabine (53.1%), indicating that BCG is more effective for this condition.

Gemcitabine was better tolerated than BCG, with fewer patients needing delayed treatment or withdrawal, suggesting it could be a suitable alternative for those who cannot tolerate BCG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bacillus Calmette-Guérin versus gemcitabine for intravesical therapy in high-risk superficial bladder cancer: a randomised prospective study. Porena, M., Del Zingaro, M., Lazzeri, M., et al.[2022]

The combination of gemcitabine, cisplatin, and lapatinib (GCL) as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) was found to be excessively toxic, leading to the early termination of the trial after enrolling six patients.

Despite attempts to reduce the lapatinib dose to improve tolerance, the treatment still resulted in significant grade 3/4 toxicities, including diarrhea, nausea/vomiting, and thrombocytopenia, indicating that this combination therapy may not be safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin, Gemcitabine, and Lapatinib as Neoadjuvant Therapy for Muscle-Invasive Bladder Cancer. Narayan, V., Mamtani, R., Keefe, S., et al.[2022]

Citations

1. firstwordpharma.com firstwordpharma.com/story/6320946

Lilly to present new clinical data for Verzenio (abemaciclib ... In a poster presentation, Lilly will share updated safety and efficacy results from the Phase 1a/1b study of LY4170156 in patients with platinum ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04238819

NCT04238819 | A Study of Abemaciclib (LY2835219) in ... The study's purpose is to see if the drug, abemaciclib, is safe and effective when given with other drugs to kill cancer cells.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5409046/

CDK4/6 Inhibitors in Cancer Therapy: A Novel Treatement ... Patients with metastatic bladder cancer (mBC) treated with cisplatin-based chemotherapy have a limited median survival of only around 14 months ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-01489

A Study of Abemaciclib (LY2835219) in Combination With ... The study's purpose is to see if the drug, abemaciclib, is safe and effective when given with other drugs to kill cancer cells.

5. urotoday.com urotoday.com/video-lectures/advanced-bladder-cancer/video/mediaitem/4907-clonevo-study-targeting-cyclin-d1-amplifications-in-bladder-cancer-with-abemaciclib-bishoy-faltas.html

CLONEVO Study: Targeting Cyclin D1 Amplifications in ... The study enrolled patients for 4-8 weeks of oral abemaciclib before cystectomy, achieving 31% pathologic downstaging with just four weeks of treatment and ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK601722/

Clinical Review - Abemaciclib (Verzenio) - NCBI Bookshelf - NIH At the interim analysis 1 for OS (April 1, 2021), OS data were immature. There were 95 deaths (42 in the abemaciclib + ET arm and 53 in the ET arm) in ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.4520

CLONEVO: Preoperative abemaciclib for cisplatin- ... This first trial of short-term preoperative abema in MIBC demonstrated promising efficacy and tolerability while modulating cell cycle-dependent pathways.