Eribulin + Chemotherapy for Bladder Cancer

Recruiting at 304 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

Trial Summary

What is the purpose of this trial?

This phase III trial compares the usual chemotherapy treatment to eribulin plus gemcitabine in treating patients with urothelial cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Chemotherapy drugs, such as eribulin, gemcitabine, docetaxel, paclitaxel, and sacituzumab govitecan 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. This trial aims to see whether adding eribulin to standard of care chemotherapy may work better in treating patients with metastatic urothelial cancer.

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.

What data supports the effectiveness of the drug combination Eribulin and chemotherapy for bladder cancer?

Research shows that combinations of drugs like docetaxel and gemcitabine have been used effectively in treating advanced bladder cancer, with promising results in terms of response rates. These drugs are part of the combination being studied, suggesting potential effectiveness for the new treatment. ^{1 2 3 4 5}

Is the combination of Eribulin and chemotherapy safe for treating bladder cancer?

Studies have shown that the combination of gemcitabine and docetaxel, which are part of the chemotherapy regimen, has been evaluated for safety in treating advanced bladder cancer. These studies generally focus on the side effects and how well patients tolerate the treatment, indicating that while there are side effects, the treatment is considered manageable for many patients. ^{2 5 6 7 8}

What makes the Eribulin + Chemotherapy treatment unique for bladder cancer?

This treatment is unique because it combines eribulin, a drug not commonly used for bladder cancer, with other chemotherapy agents like gemcitabine and docetaxel, offering an option for patients who cannot use standard cisplatin-based treatments. ^{1 2 9 10 11}

Research Team

Sarmad Sadeghi

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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 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]

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 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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Weekly chemotherapy with docetaxel, gemcitabine and cisplatin in advanced transitional cell urothelial cancer: a phase II trial. [2022]

2. United States 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. [2023]

3. France pubmed.ncbi.nlm.nih.gov

[The role of new drugs in the treatment of locally advanced urothelial tumors of the bladder]. [2022]

4. United States 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. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Gemcitabine and docetaxel as first-line treatment for advanced urothelial carcinoma: a phase II study. [2022]

6. England 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. [2022]

7. Switzerland 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. [2022]

8. United States 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. [2022]

9. 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]

10. England pubmed.ncbi.nlm.nih.gov

Gemcitabine in the treatment of bladder cancer. [2022]

11. Switzerland 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. [2022]