Eribulin Mesylate for Advanced Bladder Cancer

Not currently recruiting at 27 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the chemotherapy drug eribulin mesylate works for patients with advanced bladder cancer that cannot be treated with surgery. The researchers aim to determine if this drug can effectively stop or slow cancer growth, particularly in patients with kidney issues. The trial is suitable for patients with measurable urothelial cancer that has spread and who have previously undergone up to two chemotherapy treatments, including at least one platinum-based option. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering patients the opportunity to be among the first to receive this potentially beneficial therapy.

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.

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

Research has shown that eribulin mesylate is generally well-tolerated by patients with advanced bladder cancer. In past studies, 78.8% of patients completed the entire treatment. Common side effects included painful urination and tiredness, but most patients managed these effectively.

Additionally, eribulin mesylate has a low rate of nerve damage, occurring in about 25% of patients and mostly mild. No significant allergic reactions were reported. Overall, the treatment appears safe, with side effects that most patients can handle. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for advanced bladder cancer, which often include chemotherapy regimens like cisplatin or gemcitabine, eribulin mesylate offers a unique approach. Eribulin is derived from a natural marine sponge and works by disrupting the microtubule network in cancer cells, which is crucial for their division and growth. This mechanism of action is different from traditional chemotherapy, potentially leading to fewer side effects and improved outcomes. Researchers are excited about eribulin because it could provide a new line of defense against cancer cells that have become resistant to conventional therapies.

What evidence suggests that eribulin mesylate might be an effective treatment for advanced bladder cancer?

Research shows that eribulin mesylate, the treatment under study in this trial, might help treat advanced bladder cancer. Studies have found that eribulin can boost the body's natural killer cells, which are part of the immune system and help fight cancer. While this trial focuses on eribulin mesylate alone, other studies suggest that combining it with cancer drugs like gemcitabine and cisplatin may be more effective than using those drugs alone. Additionally, combining eribulin with treatments like atezolizumab or avelumab has shown promise in improving results. Overall, early evidence suggests that eribulin mesylate could be a helpful option for treating advanced bladder cancer. ^{1 3 6 7 8}

Who Is on the Research Team?

David I. Quinn

Principal Investigator

City of Hope Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11592921/

Low-Dose Eribulin Promotes NK Cell-Mediated ...

Mechanistically, eribulin enhanced NK cell migration and cytotoxicity against BCa cells, promoted an anti-tumor NK cell phenotype, and reduced ...

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withpower.com

withpower.com/trial/eribulin-mesylate-for-advanced-bladder-cancer-b5c1d

Eribulin Mesylate for Advanced Bladder Cancer

In a long-term follow-up of the BLC2001 study involving 101 patients with advanced urothelial carcinoma, erdafitinib demonstrated a 40% objective response rate, ...

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A trial looking at eribulin mesylate for advanced bladder ...

The researchers think that combining eribulin mesylate with gemcitabine and cisplatin may be better than gemcitabine and cisplatin alone. The aim of this trial ...

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clinicaltrials.gov/study/NCT03237780

Study Details | NCT03237780 | Atezolizumab With or ...

Giving atezolizumab and eribulin mesylate may work better at treating urothelial cancer compared to atezolizumab alone. Detailed Description. PRIMARY OBJECTIVES ...

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sciencedirect.com

sciencedirect.com/science/article/abs/pii/S2405456921000626

Urothelial Cancer Avelumab in Combination with Eribulin ...

The combination of eribulin and avelumab shows promise in mUC. We observed that treatment was better tolerated and efficacious at lower doses of eribulin.

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01126749

Study Details | NCT01126749 | Eribulin Mesylate ...

The purpose of this study is to determine whether Patients with Locally Advanced or Metastatic Bladder Cancer who receive Eribulin Mesylate Administered in ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4557013/

Eribulin in Cancer Treatment - PMC - PubMed Central

Eribulin was found to be safe, with low incidence of neuropathy (25%, all G 1/2) or cumulative toxicities and with an absence of hypersensitivity reaction [50].

8.

withpower.com

withpower.com/trial/phase-2-carcinoma-9-2006-be5f1?lat=34.60184&lng=-117.81218

Eribulin Mesylate for Advanced Bladder Cancer

What safety data exists for Eribulin Mesylate in humans? A trial sponsored by the National Cancer Institute evaluated the safety of a combination of ...