Eribulin + Chemotherapy for Bladder Cancer

Recruiting at 324 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must be taking: Enfortumab vedotin, PD1/PDL1 antibody

Must not be taking: CYP3A inhibitors, CYP2C8 inducers

Disqualifiers: Pregnancy, CNS treatment, QTc prolongation, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: Variable, based on disease progression or toxicity

184 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding eribulin (a type of chemotherapy) to the usual chemotherapy can more effectively treat urothelial cancer that has spread. Participants are divided into three groups: one receiving standard chemotherapy, one receiving only eribulin, and another receiving both eribulin and gemcitabine. The trial aims to determine if these combinations can halt the growth or spread of cancer cells. Suitable candidates have urothelial cancer that has metastasized and have not responded to other treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are taking strong or moderate CYP3A or CYP2C8 inhibitors or inducers, you may need to stop them at least 2 weeks before starting the trial if you are assigned to certain treatment groups.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that eribulin is generally well-tolerated by patients. In past studies, about 79% of patients completed their full treatment cycles. Common side effects included fatigue and painful urination. However, severe neutropenia, a low white blood cell count, was a significant side effect, occurring in 12% of patients and lasting more than a week for some.

The FDA has already approved eribulin for treating advanced breast cancer, providing extensive safety information about its use. Gemcitabine, when combined with eribulin, has been studied for its effectiveness in treating bladder cancer. Although limited safety information exists on this combination, eribulin's prior approval and general tolerability are promising signs.

Overall, the treatment appears manageable, and many patients tolerate it well. However, like any treatment, it carries risks, and potential participants should discuss these with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer new combinations and approaches for tackling bladder cancer. Unlike traditional chemotherapies often used in this condition, like cisplatin or carboplatin with gemcitabine, the investigational treatments include eribulin, which works by inhibiting microtubule dynamics essential for cell division. In Arm II, eribulin is used alone, providing a simpler regimen that might reduce side effects. Arm III combines eribulin with gemcitabine, potentially enhancing effectiveness by attacking cancer cells through multiple mechanisms. These innovative approaches could lead to better outcomes and broaden the options available for patients battling bladder cancer.

What evidence suggests that this trial's treatments could be effective for metastatic urothelial cancer?

Research has shown that combining eribulin with gemcitabine, which participants in this trial may receive, may effectively treat advanced bladder cancer. In one study, this combination helped 50% of patients who couldn't take cisplatin, a common cancer drug. These patients lived for about 11.9 months on average, and their cancer did not worsen for about 5.3 months. This suggests the treatment might help control the cancer for a while. Eribulin, tested in this trial, is already used to treat other cancers, such as breast cancer, where it has helped patients live longer. This indicates it could also benefit bladder cancer patients. ^{3 6 7 8 9}

Who Is on the Research Team?

Sarmad Sadeghi

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults with metastatic urothelial cancer who've had platinum-based and PD1/PDL1 antibody therapy, possibly enfortumab vedotin. They should have good organ function, no immediate CNS treatment needs, not be pregnant or breastfeeding, and willing to use contraception. Excluded are those with recent gemcitabine progression or unresolved toxicities from past treatments.

Inclusion Criteria

I am not taking, nor plan to take, certain medications that affect enzyme levels if I'm assigned to a specific treatment group.

Participant must have complete blood count (CBC), complete metabolic panel including liver function tests, and lactate dehydrogenase (LDH) obtained with 28 days prior to registration

My scans show metastatic urothelial carcinoma.

Exclusion Criteria

I am not pregnant or nursing and will use effective birth control during and after the study.

Participants must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

Participant must not have a known history of corrected QT (QTc) prolongation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive chemotherapy regimens based on the arm they are randomized to, with cycles repeating every 21 or 28 days in the absence of disease progression or unacceptable toxicity.

Variable, based on disease progression or toxicity

Multiple visits per cycle for IV administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 6 months for 2 years, then annually until death or 3 years from registration.

Up to 3 years

Every 6 months for 2 years, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• Eribulin Mesylate
• Gemcitabine Hydrochloride
• Paclitaxel

Trial Overview The study compares standard chemotherapy alone versus adding the drug Eribulin either alone or with Gemcitabine in treating metastatic urothelial cancer. It aims to find out if Eribulin can improve outcomes when combined with usual chemotherapy drugs.

How Is the Trial Designed?

Group I: Arm III (eribulin, gemcitabine) Experimental Treatment 6 Interventions

Patients receive eribulin IV over 2-5 minutes and gemcitabine IV on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI throughout the trial and may undergo bone scan at the discretion of the treating physician. Patients also undergo blood and urine sample collection on the trial.

Group II: Arm II (eribulin) Experimental Treatment 5 Interventions

Patients receive eribulin IV over 2-5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI throughout the trial and may undergo bone scan at the discretion of the treating physician. Patients also undergo blood and urine sample collection on the trial. (CLOSED TO ACCRUAL)

Group III: Arm I (standard of care chemotherapy) Active Control 8 Interventions

See Detailed Description.

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

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

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

Gemcitabine, a newer chemotherapy agent, has shown promising activity against bladder cancer, both as a single agent and in combination with cisplatin, offering a favorable toxicity profile compared to traditional treatments.

The standard treatment for advanced bladder cancer in the US remains the M-VAC regimen, but ongoing trials are exploring the effectiveness of gemcitabine combined with other agents, which may lead to improved treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine in the treatment of bladder cancer. Ryan, CW., Vogelzang, NJ.[2022]

In a Phase II trial involving 29 patients with advanced urothelial carcinoma, the combination of gemcitabine and docetaxel showed an overall response rate of 17%, indicating it can be an effective second-line treatment option for this patient group.

The treatment was associated with moderate toxicity, primarily granulocytopenia, anorexia, and fatigue, highlighting the need for careful monitoring, especially due to reported thromboembolic symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of gemcitabine and docetaxel in patients with advanced carcinoma of the urothelium: a trial of the Eastern Cooperative Oncology Group. Dreicer, R., Manola, J., Schneider, DJ., et al.[2022]

In a study of 312 patients with high-risk non-muscle-invasive bladder cancer, treatment with sequential intravesical gemcitabine and docetaxel resulted in significantly better high-grade recurrence-free survival compared to BCG therapy, with 81% recurrence-free at 24 months versus 69% for BCG.

Gemcitabine and docetaxel also had a lower treatment discontinuation rate (2.9%) compared to BCG (9.2%), suggesting it may be a more tolerable option during the ongoing BCG shortage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Sequential Intravesical Gemcitabine and Docetaxel vs Bacillus Calmette-Guérin for the Treatment of Patients With High-Risk Non-Muscle-Invasive Bladder Cancer. McElree, IM., Steinberg, RL., Mott, SL., et al.[2023]

The sequential treatment of gemcitabine and cisplatin followed by docetaxel showed a promising objective response rate of 55.2% in 38 patients with advanced urothelial carcinoma, indicating its efficacy as a first-line therapy.

The treatment was generally well tolerated, with manageable side effects; although 27% experienced severe neutropenia during the GP regimen, there were no toxic deaths reported, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential gemcitabine and cisplatin followed by docetaxel as first-line treatment of advanced urothelial carcinoma: a multicenter phase II study of the Hellenic Oncology Research Group. Boukovinas, I., Androulakis, N., Vamvakas, L., et al.[2022]

In a phase 2 trial involving 22 patients with advanced urothelial cancer who had previously failed platinum-based chemotherapy, the combination of docetaxel and ifosfamide showed an objective response rate of 25%, with 20% achieving complete responses, particularly in those with lymph node-only recurrences.

The treatment was well tolerated, with mild to moderate side effects, and serious toxicities were relatively low, suggesting that this combination therapy could be a viable option for patients with specific recurrence patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel and ifosfamide as second line treatment for patients with advanced or metastatic urothelial cancer after failure of platinum chemotherapy: a phase 2 study. Krege, S., Rembrink, V., Börgermann, C., et al.[2019]

In a study of 60 patients with non-muscle invasive bladder cancer (NMIBC), the combination of intravesical gemcitabine and docetaxel (Gem/Doce) demonstrated better quality of life outcomes compared to the traditional BCG treatment after 6 months of maintenance therapy.

The Gem/Doce treatment also resulted in fewer side effects than BCG, suggesting it could be a safer and effective alternative for NMIBC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of Life, Efficacy, and Safety of Sequential Intravesical Gemcitabine + Docetaxel versus BCG for Non-Muscle Invasive Urinary Bladder Cancer: A Pilot Study. Pareek, T., Parmar, K., Sharma, AP., et al.[2022]

Current treatments for muscle-invasive bladder cancer, including radical cystectomy and chemotherapy, have a cure rate of only about 50%, with many patients developing metastases within two years.

New agents like taxanes (paclitaxel and docetaxel) and gemcitabine show promising results in preliminary phase II studies, suggesting they could enhance treatment outcomes when combined with existing chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The role of new drugs in the treatment of locally advanced urothelial tumors of the bladder]. Antoine, EC., Khayat, D.[2022]

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 study of 31 patients with advanced bladder cancer, the combination of gemcitabine and vinorelbine chemotherapy showed a 47.6% objective response rate in patients who had not received prior chemotherapy, indicating significant efficacy for this treatment.

The treatment was well tolerated, with only 16.1% of patients experiencing severe leukopenia and 12.9% suffering from significant nonhematologic toxicity, suggesting a favorable safety profile for those unsuitable for cisplatin-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine plus vinorelbine chemotherapy in patients with advanced bladder carcinoma who are medically unsuitable for or who have failed cisplatin-based chemotherapy. Türkölmez, K., Bedük, Y., Baltaci, S., et al.[2022]

In a study of 35 patients with advanced transitional cell carcinoma (TCC), a combination of weekly docetaxel, gemcitabine, and cisplatin resulted in a high objective response rate of 65.6%, with 28.5% achieving a complete response.

The treatment was associated with moderate toxicity, including grade 3/4 neutropenia in 28.5% of patients, but no treatment-related deaths occurred, suggesting it is a safe and effective option for chemotherapy-naïve patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly chemotherapy with docetaxel, gemcitabine and cisplatin in advanced transitional cell urothelial cancer: a phase II trial. Pectasides, D., Glotsos, J., Bountouroglou, N., et al.[2022]

The combination of gemcitabine and docetaxel showed a 51.6% overall response rate in 31 patients with advanced urothelial carcinoma, indicating significant efficacy as a first-line treatment.

The treatment was well tolerated, with manageable hematologic toxicities and no toxic deaths, suggesting it could be a safer alternative for patients with compromised renal function or cardiovascular issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and docetaxel as first-line treatment for advanced urothelial carcinoma: a phase II study. Ardavanis, A., Tryfonopoulos, D., Alexopoulos, A., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS4617

A phase III randomized trial of eribulin (E) with gemcitabine ... A phase II CTEP study of gemcitabine-eribulin (GE) in cisplatin ineligible mUC showed ORR of 50%, median OS of 11.9 mo and median PFS of 5.3 mo ...

2. mdpi.com mdpi.com/1660-3397/13/8/5016

Eribulin in Cancer Treatment Eribulin induced significant differences in event-free survival distribution in 29 of 35 (83%) of the solid tumors and in 8 of 8 (100%) of ALL xenografts, as ...

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

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 ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39594830/

Low-Dose Eribulin Promotes NK Cell-Mediated Therapeutic ... Results: We found that localized eribulin instillation significantly reduces bladder tumor burden and improves survival in primary BCa in an NK ...

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

Low-Dose Eribulin Promotes NK Cell-Mediated ... Eribulin is currently used in the treatment of locally advanced or metastatic breast cancer, where it has demonstrated a survival advantage ...

6. halaven.com halaven.com/-/media/Files/Halaven/HALAVEN-Safety-and-Dosing-Brochure.pdf?la=en

SAFETY & DOSING GUIDE Selected Safety Information. Warnings and Precautions. Neutropenia: Severe neutropenia (ANC <500/mm3) lasting >1 week occurred in 12% of patients with mBC.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2010/201532lbl.pdf

Halaven (erbulin mesylate) Injection - accessdata.fda.gov The safety of HALAVEN was not studied in patients with severe ... HALAVEN (eribulin mesylate) Injection is a non-taxane microtubule dynamics inhibitor.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3432792/

Eribulin mesylate in patients with refractory cancers Eribulin mesylate, administered on Days 1 and 8 of a 21-day cycle, exhibits manageable tolerability at 1.4 mg/m 2 . DLT was neutropenia.

9. halaven.com halaven.com/-/media/Files/Halaven/HALAVEN-Full-Prescribing-Information.pdf

HIGHLIGHTS OF PRESCRIBING INFORMATION The pharmacokinetics (PK) of eribulin were within range of values of adult patients with metastatic liposarcoma or other tumors given the same dose per body ...