Eribulin Mesylate for Advanced Bladder Cancer

Recruiting at 26 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Platinum-based chemotherapy

Must not be taking: Antiretrovirals

Disqualifiers: Brain metastasis, Uncontrolled illness, HIV, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 14

Duration: 21 days per cycle

132 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I/II trial studies the effect of eribulin mesylate and to see how well it works in treating patients with cancer of the urothelium that has spread to nearby tissue (locally advanced) or to other places in the body (metastatic)and kidney dysfunction. Drugs used in chemotherapy, such as eribulin mesylate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Chemotherapy drugs may have different effects in patients who have changes in their kidney function.

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

The trial protocol does not specify if you need to stop taking your current medications. However, the eligibility of patients taking medications that might affect the trial drug will be reviewed by the principal investigator.

What data supports the effectiveness of the drug Eribulin Mesylate for advanced bladder cancer?

A study showed that a combination of gemcitabine and eribulin was effective and tolerable for patients with metastatic urothelial carcinoma who couldn't use cisplatin-based treatments, suggesting potential benefits of eribulin in similar conditions. ^{1 2 3 4 5}

What safety data exists for Eribulin Mesylate in humans?

A trial sponsored by the National Cancer Institute evaluated the safety of a combination of gemcitabine and Eribulin Mesylate in patients with metastatic urothelial carcinoma, indicating that it has been tested for safety in humans. ^{1 3 6 7 8}

How is the drug Eribulin Mesylate different from other treatments for advanced bladder cancer?

Eribulin Mesylate is unique because it is being studied in combination with gemcitabine for patients who cannot receive cisplatin, a common but often ineligible treatment for advanced bladder cancer. This combination aims to offer a new option with potentially better tolerability and effectiveness for these patients. ^{1 3 9 10 11}

Research Team

David I. Quinn

Principal Investigator

City of Hope Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with advanced or metastatic urothelial cancer that can't be removed by surgery. They should have had some prior chemotherapy, but not the drug being tested. Participants need to have a life expectancy over 6 months, acceptable organ function, and agree to use contraception. Those with HIV on antiretroviral therapy, unstable brain metastasis, or severe illnesses are excluded.

Inclusion Criteria

My doctor expects me to live more than 6 months.

My bladder cancer cannot be removed with surgery and has spread.

My cancer is confirmed to be urothelial carcinoma.

Exclusion Criteria

I am HIV-negative or if positive, not on antiretroviral therapy and have a CD4+ count > 500/mm3.

Patients may not be receiving any other investigational agents

I am not pregnant or breastfeeding if I am to be treated with E7389.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive eribulin mesylate intravenously on days 1 and 8 of a 21-day cycle

21 days per cycle

2 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Monthly visits for 12 months, then every 3 months for up to 24 months

Treatment Details

Interventions

• Eribulin Mesylate

Trial Overview The trial is testing Eribulin Mesylate's effectiveness in patients with kidney dysfunction and locally advanced or metastatic urothelial cancer. It includes laboratory biomarker analysis and pharmacological studies to understand how the drug works when kidneys aren't functioning normally.

Participant Groups

Group I: Treatment (eribulin mesylate) Experimental Treatment 3 Interventions

Patients receive eribulin mesylate IV over 1-2 minutes on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Eribulin Mesylate is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Halaven for:

• Metastatic breast cancer
• Unresectable or metastatic liposarcoma

Approved in European Union as Halaven for:

• Locally advanced or metastatic breast cancer
• Adult patients with unresectable liposarcoma who have received prior anthracycline containing therapy (unless unsuitable) for advanced or metastatic disease

Approved in Canada as Halaven for:

• Metastatic breast cancer
• Unresectable or metastatic liposarcoma

Approved in Japan as Halaven for:

• Inoperable or recurrent breast cancer
• Soft tissue sarcoma (liposarcoma)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a trial involving 24 patients with metastatic urothelial carcinoma who were ineligible for cisplatin-based treatments, the combination of gemcitabine and eribulin resulted in a 50% objective response rate, indicating that half of the patients showed a positive response to the treatment.

The median overall survival for these patients was 11.9 months, suggesting that this treatment regimen may provide a viable option for patients who cannot tolerate cisplatin, although common side effects included fatigue, neutropenia, and anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II California Cancer Consortium Trial of Gemcitabine-Eribulin Combination in Cisplatin-Ineligible Patients With Metastatic Urothelial Carcinoma: Final Report (NCI-9653). Sadeghi, S., Groshen, SG., Tsao-Wei, DD., et al.[2022]

In a long-term follow-up of the BLC2001 study involving 101 patients with advanced urothelial carcinoma, erdafitinib demonstrated a 40% objective response rate, indicating its efficacy in this patient population with specific FGFR alterations.

The safety profile of erdafitinib remained consistent over time, with 71% of patients experiencing grade 3-4 adverse events, but no new safety concerns were identified, suggesting it is a manageable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma: long-term follow-up of a phase 2 study. Siefker-Radtke, AO., Necchi, A., Park, SH., et al.[2022]

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 Phase 1 safety study involving six patients with non-muscle-invasive bladder cancer (NMIBC), intravesical administration of pembrolizumab was well tolerated, with no dose-limiting toxicities observed during dose escalation.

The treatment resulted in low-grade adverse events such as dysuria and fatigue, and importantly, there was no evidence of systemic absorption or immune effects, suggesting a localized action of the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PemBla: A Phase 1 study of intravesical pembrolizumab in recurrent non-muscle-invasive bladder cancer. Woodcock, VK., Chen, JL., Purshouse, K., et al.[2023]

The combination of gemcitabine and irinotecan (Irinogem) showed promising efficacy in treating metastatic bladder cancer, with 8 out of 13 evaluable patients achieving an objective response, including 2 complete responses and 6 partial responses, and a median progression-free survival of 8.78 months.

The treatment was associated with manageable toxicity, with no toxic deaths reported, although some patients experienced significant side effects like neutropenia and diarrhea. However, the study's early closure due to funding issues limits the ability to draw definitive conclusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of gemcitabine and irinotecan in patients with locally advanced or metastatic bladder cancer. Chaudhary, UB., Verma, N., Keane, T., et al.[2022]

References

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

Phase II California Cancer Consortium Trial of Gemcitabine-Eribulin Combination in Cisplatin-Ineligible Patients With Metastatic Urothelial Carcinoma: Final Report (NCI-9653). [2022]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma: long-term follow-up of a phase 2 study. [2022]

3. 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]

4. Pakistan pubmed.ncbi.nlm.nih.gov

Clinical efficacy of intravesical gemcitabine combined with ubenimex in patients with non-muscle-invasive bladder carcinoma after transurethral resection of bladder tumor. [2022]

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

Trastuzumab, paclitaxel, carboplatin, and gemcitabine in advanced human epidermal growth factor receptor-2/neu-positive urothelial carcinoma: results of a multicenter phase II National Cancer Institute trial. [2022]

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

PemBla: A Phase 1 study of intravesical pembrolizumab in recurrent non-muscle-invasive bladder cancer. [2023]

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

A phase II study of gemcitabine and irinotecan in patients with locally advanced or metastatic bladder cancer. [2022]

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

Safety of repeat blue light cystoscopy with hexaminolevulinate (HAL) in the management of bladder cancer: Results from a phase III, comparative, multi-center study. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Gemcitabine for unresectable, locally advanced or metastatic bladder cancer. [2022]

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

Paclitaxel and gemcitabine chemotherapy for advanced transitional-cell carcinoma of the urothelial tract: a phase II trial of the Minnie pearl cancer research network. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Second-line systemic therapy for metastatic urothelial carcinoma of the bladder. [2013]