Atezolizumab +/− Eribulin Mesylate for Bladder Cancer

Recruiting at 21 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Immunostimulants

Disqualifiers: Organ transplant, Autoimmune disease, Cardiovascular disease, Active infections, others

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

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 24

Duration: Up to 52 weeks

72 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, certain treatments like systemic immunosuppressive medications and some investigational agents must be stopped before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Atezolizumab for bladder cancer?

Atezolizumab has shown effectiveness in treating advanced bladder cancer, with studies indicating a 15% response rate and 36% one-year survival in patients who had previously received chemotherapy. It is approved for use in patients who cannot take cisplatin, with a 24% response rate and 57% one-year survival in this group. ^{1 2 3 4 5}

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

Atezolizumab (also known as Tecentriq) has been shown to have a favorable safety profile in treating advanced bladder cancer, with manageable side effects compared to traditional chemotherapy. While specific safety data for the combination with Eribulin Mesylate (Halaven) in bladder cancer is not provided, Atezolizumab alone has been well-tolerated in clinical trials. ^{1 2 3 4 6}

How is the drug Atezolizumab +/− Eribulin Mesylate unique for bladder cancer treatment?

Atezolizumab is unique because it is a monoclonal antibody that blocks PD-L1, helping the immune system attack bladder cancer cells more effectively, and it has shown durable responses in patients who have not responded to traditional chemotherapy. It is approved for use in patients who cannot tolerate cisplatin or whose cancer has progressed after platinum-based chemotherapy, offering a new option where few existed before. ^{1 2 3 4 5}

What is the purpose of this trial?

This phase II trial studies the side effects of atezolizumab with or without eribulin mesylate and how well they work in treating patients with urothelial cancer that has come back (recurrent), spread to nearby tissues or lymph nodes (locally advanced), or spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, 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. Giving atezolizumab and eribulin mesylate may work better at treating urothelial cancer compared to atezolizumab alone.

Research Team

Anishka D'Souza

Principal Investigator

City of Hope Comprehensive Cancer Center LAO

Eligibility Criteria

Adults over 18 with recurrent, locally advanced or metastatic urothelial cancer who've had platinum-based treatment within the last year. They must have recovered from previous treatments' side effects, have a life expectancy of at least 12 weeks, and measurable disease. HIV-positive patients can join if they meet certain criteria. Exclusions include autoimmune diseases, severe heart or liver conditions, recent major surgery or vaccinations, current serious infections, history of lung problems like pneumonitis, and prior bone marrow or organ transplants.

Inclusion Criteria

My cancer is advanced and cannot be removed by surgery.

I can provide a sample of my tumor for testing.

My cancer came back or got worse within a year after platinum-based treatment.

Exclusion Criteria

I do not have any unmanaged ongoing illnesses.

I have had a bone marrow or organ transplant.

I have recently undergone chemotherapy, radiotherapy, or targeted therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive atezolizumab with or without eribulin mesylate in 21-day cycles

Up to 52 weeks

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

Every 3 or 6 months

Treatment Details

Interventions

• Atezolizumab
• Eribulin Mesylate

Trial Overview The trial is testing how well Atezolizumab works alone versus combined with Eribulin Mesylate in treating urothelial cancer that has returned after treatment or spread to other parts of the body. Atezolizumab is an immunotherapy drug while Eribulin Mesylate is a chemotherapy drug; both aim to stop cancer growth by different mechanisms.

Participant Groups

Group I: Arm II (atezolizumab, eribulin mesylate) Experimental Treatment 5 Interventions

Patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle and eribulin mesylate IV over 2-3 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and CT with contrast throughout the trial. Patients may undergo biopsy during screening and on study.

Group II: Arm I (atezolizumab) Experimental Treatment 4 Interventions

Patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and CT with contrast throughout the trial. Patients may undergo biopsy during screening and on study.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]

Atezolizumab, an anti-PD-L1 monoclonal antibody, has shown durable responses in treating locally advanced and metastatic urothelial cancer, especially in patients who have failed platinum-based chemotherapy or are ineligible for cisplatin.

The treatment with atezolizumab has a more favorable toxicity profile compared to traditional cytotoxic chemotherapy, making it a promising option for patients with advanced bladder cancer, although further research is needed to identify additional predictive markers for response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab in invasive and metastatic urothelial carcinoma. Crist, M., Balar, A.[2019]

Atezolizumab, a monoclonal antibody targeting PD-L1, showed a 23% response rate and a median overall survival of 15.9 months in 119 patients with metastatic urothelial cancer who were unfit for cisplatin, indicating its efficacy as a front-line treatment.

In patients whose tumors progressed after first-line chemotherapy, atezolizumab had a 15% response rate and a median overall survival of 7.9 months, with better outcomes (26% response rate) in those with high PD-L1 expression, demonstrating its potential effectiveness based on biomarker status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Atezolizumab (Tecentriq®): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. Bernard-Tessier, A., Bonnet, C., Lavaud, P., et al.[2019]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

In a study of 115 patients with metastatic urothelial carcinoma treated with atezolizumab (ATZ) after failing first-line chemotherapy, the objective response rate was 28.7%, indicating that ATZ is effective in this patient population.

The treatment was well tolerated, with 98% of patients experiencing adverse events, but only 21.2% had severe (grade 3-4) treatment-related adverse events, suggesting a manageable safety profile similar to previous clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences. Tural, D., Ölmez, ÖF., Sümbül, AT., et al.[2022]

References

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

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]

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

Atezolizumab in invasive and metastatic urothelial carcinoma. [2019]

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

[Atezolizumab (Tecentriq®): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. [2019]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. [2019]

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

Safety and Efficacy of Atezolizumab in Understudied Populations with Pretreated Urinary Tract Carcinoma: Subgroup Analyses of the SAUL Study in Real-World Practice. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences. [2022]