Abemaciclib for Bladder Cancer

(CLONEVO Trial)

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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

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)

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.

What data supports the idea that Abemaciclib for Bladder Cancer is an effective drug?

The available research does not provide specific data supporting the effectiveness of Abemaciclib for treating bladder cancer. Instead, it discusses other treatments like chemotherapy and targeted therapies for bladder cancer. For example, cisplatin and gemcitabine are commonly used, and new therapies are being developed to target specific genetic changes in bladder cancer. While Abemaciclib is used for other conditions, there is no direct evidence here showing its effectiveness for bladder cancer. ^{1 2 3 4 5}

What safety data exists for Abemaciclib in bladder cancer treatment?

The provided research does not contain specific safety data for Abemaciclib (also known as Verzenio, LY2835219, Ramiven) in the treatment of bladder cancer. The studies focus on other treatments such as gemcitabine, cisplatin, lapatinib, dovitinib, and various immunotherapies for bladder cancer. Therefore, no safety data for Abemaciclib in this context is available from the given research. ^{4 6 7 8 9}

Is Abemaciclib a promising drug for bladder cancer?

The provided research articles do not mention Abemaciclib as a treatment for bladder cancer. They focus on other drugs like gemcitabine, cisplatin, and emerging targeted therapies. Therefore, there is no information here to suggest that Abemaciclib is a promising drug for bladder cancer. ^{2 8 9 10 11}

How is the drug Abemaciclib unique for treating bladder cancer?

Abemaciclib is unique for treating bladder cancer because it is a targeted therapy that works by inhibiting specific proteins (CDK4 and CDK6) involved in cell division, which is different from traditional chemotherapy that targets all rapidly dividing cells. This approach may offer a more personalized treatment option compared to the standard chemotherapy regimens like cisplatin and gemcitabine. ^{2 8 9 10 12}

Research Team

Bishoy Faltas, MD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

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

I am 18 years old or older.

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.

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

References

1. Netherlands 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. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

The role of genomics in the management of advanced bladder cancer. [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Molecular Oncology of Bladder Cancer from Inception to Modern Perspective. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Systemic therapy in muscle-invasive and metastatic bladder cancer: current trends and future promises. [2017]

5. Switzerland 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. [2021]

6. United States 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. [2019]

7. Czech Republic pubmed.ncbi.nlm.nih.gov

[Immunotherapy for Bladder Cancer]. [2019]

8. China 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. [2023]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Cisplatin, Gemcitabine, and Lapatinib as Neoadjuvant Therapy for Muscle-Invasive Bladder Cancer. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Bacillus Calmette-Guérin versus gemcitabine for intravesical therapy in high-risk superficial bladder cancer: a randomised prospective study. [2022]

11. United States 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. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

A phase II trial of neoadjuvant nab-paclitaxel, carboplatin, and gemcitabine (ACaG) in patients with locally advanced carcinoma of the bladder. [2022]