18 Participants Needed

Pemetrexed + Avelumab for Bladder Cancer

AS
Overseen ByAmishi Shah
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: M.D. Anderson Cancer Center
Must be taking: Folic acid, Vitamin B12, Dexamethasone
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

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, you must be able to interrupt nonsteroidal anti-inflammatory drugs (NSAIDs) around the time of pemetrexed administration. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Pemetrexed and Avelumab for bladder cancer?

Avelumab has been shown to prolong overall survival in advanced urothelial carcinoma when used as a maintenance treatment after initial chemotherapy. Pemetrexed has demonstrated a favorable response rate of about 30% with minimal toxicity in advanced urothelial carcinoma, suggesting potential effectiveness when combined with other treatments.12345

Is the combination of Pemetrexed and Avelumab safe for humans?

Pemetrexed has shown minimal toxicity when used alone for advanced urothelial cancer, and it has been used safely in combination with other drugs like cisplatin. Avelumab, also known as Bavencio, is generally considered safe as it is approved for use in other conditions, but specific safety data for the combination of Pemetrexed and Avelumab in bladder cancer is not provided in the available research.36789

How is the drug combination of Pemetrexed and Avelumab unique for treating bladder cancer?

The combination of Pemetrexed and Avelumab is unique because it pairs a chemotherapy drug (Pemetrexed) with an immune checkpoint inhibitor (Avelumab), which may enhance the body's immune response against bladder cancer cells, potentially offering a novel approach compared to traditional chemotherapy alone.1361011

What is the purpose of this trial?

This phase II trial studies how well pemetrexed and avelumab work in treating patients with MTAP-deficient urothelial cancer that has spread to other places in the body. Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving pemetrexed and avelumab may work better in treating patients with MTAP-deficient urothelial cancer.

Research Team

AY

Amishi Y. Shah

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with MTAP-deficient metastatic urothelial cancer, who can stop NSAIDs as required, have measurable disease, normal organ function tests, and no severe autoimmune diseases. Participants must not be pregnant or breastfeeding and agree to use effective contraception.

Inclusion Criteria

Platelets >= 100 x 10^9/L.
I have a mild or well-controlled autoimmune condition that doesn't majorly affect my immune system.
I can stop taking NSAIDs as required around my pemetrexed treatment.
See 14 more

Exclusion Criteria

I haven't taken high doses of steroids or immunosuppressants in the last 2 weeks.
I have not had major surgery or am fully recovered if I did within the last 28 days.
True positive test results for hepatitis A, B, or C during screening.
See 15 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pemetrexed IV on day 1 and avelumab IV starting cycle 2, with cycles repeating every 21 days

Up to 2 years
Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years
Follow-up at 30 and 120 days, then every 3 months

Treatment Details

Interventions

  • Avelumab
  • Pemetrexed
Trial Overview The study examines the effectiveness of combining pemetrexed (a drug that blocks enzymes needed for cell growth) with avelumab (an immunotherapy antibody) in treating patients whose cancer has spread beyond the bladder.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (pemetrexed, avelumab)Experimental Treatment2 Interventions
Patients receive pemetrexed IV over 10 minutes on day 1. Starting cycle 2, patients also receive avelumab IV over 60 minutes. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

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

🇪🇺
Approved in European Union as Bavencio for:
  • Merkel cell carcinoma
  • Renal cell carcinoma
  • Urothelial carcinoma
🇺🇸
Approved in United States as Bavencio for:
  • Merkel cell carcinoma
  • Renal cell carcinoma
  • Urothelial carcinoma
🇯🇵
Approved in Japan as Bavencio for:
  • Merkel cell carcinoma
  • Renal cell carcinoma
  • Urothelial carcinoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials
3,107
Recruited
1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Findings from Research

Avelumab maintenance therapy after platinum-based chemotherapy in advanced urothelial carcinoma significantly improves overall response rate (ORR), progression-free survival (PFS), and overall survival (OS), especially in patients with PD-L1 positive tumors, compared to those receiving best supportive care.
While avelumab is effective, it is associated with a high rate of treatment-related adverse events (TRAEs) in 86.7% of patients, with 32.4% experiencing severe adverse events, indicating the need for careful patient monitoring during treatment.
Clinical Evaluation of Avelumab in the Treatment of Advanced Urothelial Carcinoma: Focus on Patient Selection and Outcomes.Ten Eyck, JE., Kahlon, N., Masih, S., et al.[2022]
The standard treatment for locally advanced and metastatic transitional cell carcinoma includes the four-drug combination MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) or the two-drug combination GC (gemcitabine and cisplatin).
New studies suggest that pemetrexed, either alone or in combination with gemcitabine, shows promise for improved efficacy and reduced toxicity, indicating a need for further research into these new treatment options.
Pemetrexed in transitional cell carcinoma of the urothelium.von der Maase, H.[2022]
In a phase II clinical trial involving 42 patients with advanced urothelial carcinoma, the combination of pemetrexed and cisplatin resulted in a high objective response rate of 64.3%, indicating significant efficacy as a first-line treatment.
The treatment was well tolerated, with manageable toxicity; while 28.6% of patients experienced grade 3 or 4 neutropenia, there were no cases of febrile neutropenia reported.
Phase II study of pemetrexed in combination with cisplatin in patients with advanced urothelial cancer: the PECULIAR study (KCSG 10-17).Choi, YJ., Lee, SH., Lee, JL., et al.[2018]

References

Clinical Evaluation of Avelumab in the Treatment of Advanced Urothelial Carcinoma: Focus on Patient Selection and Outcomes. [2022]
Pemetrexed in transitional cell carcinoma of the urothelium. [2022]
Phase II study of pemetrexed in combination with cisplatin in patients with advanced urothelial cancer: the PECULIAR study (KCSG 10-17). [2018]
Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer. [2023]
Current and Future Landscape of Immune Checkpoint Inhibitors in Urothelial Cancer. [2020]
A phase II trial of pemetrexed plus gemcitabine in locally advanced and/or metastatic transitional cell carcinoma of the urothelium. [2022]
FDA Approval Summary: Atezolizumab or Pembrolizumab for the Treatment of Patients with Advanced Urothelial Carcinoma Ineligible for Cisplatin-Containing Chemotherapy. [2020]
Brief communication: use of the multitargeted antifolate pemetrexed (Alimta) in genitourinary cancer. [2022]
Pembrolizumab in the treatment of advanced urothelial cancer. [2018]
Atezolizumab in invasive and metastatic urothelial carcinoma. [2019]
11.United Statespubmed.ncbi.nlm.nih.gov
Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]
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