Pemetrexed for Bladder Cancer

Overseen By Study Coordinator, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Northwestern University

Must be taking: Folic acid, Vitamin B12, Steroids

Must not be taking: Investigational agents

Disqualifiers: Prior pemetrexed, Uncontrolled illness, Cardiac disease, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 21 days per cycle

64 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how effectively the drug pemetrexed treats certain types of bladder cancer and other solid tumors that have metastasized. The researchers aim to determine if pemetrexed can shrink or halt the growth of these tumors, particularly in patients with specific genetic changes. These changes can reduce the activity of certain proteins or enzymes. Suitable candidates for this trial have metastatic bladder cancer that has not responded to other treatments and possess specific genetic mutations identified by their doctor. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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 stop taking nonsteroidal anti-inflammatory drugs (NSAIDs) or high-dose aspirin around the time of pemetrexed treatment. There is also a 28-day washout period required after stopping any prior chemotherapy, radiation, or investigational agents before starting the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Previous studies have shown that patients generally tolerate pemetrexed well. Common side effects include tiredness, nausea, and low blood cell counts, but most individuals manage these effects with standard care. Research indicates that serious side effects are rare. Pemetrexed has treated various types of cancer, and its safety is well understood from its use in other conditions. While side effects can occur, they are usually manageable and not severe for most patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pemetrexed is unique because it offers a distinct approach by disrupting the folate-dependent processes cancer cells need to multiply. Unlike traditional therapies for bladder cancer, which often involve cisplatin-based chemotherapy, pemetrexed specifically hinders the formation of DNA and RNA in cancer cells by blocking key enzymes. This targeted action might be more effective for certain patients and could result in fewer side effects compared to broader chemotherapy options. Researchers are excited about pemetrexed's potential to improve outcomes for those with bladder cancer by offering a more precise treatment pathway.

What evidence suggests that pemetrexed might be an effective treatment for bladder cancer?

Research has shown that pemetrexed, a drug that prevents cancer cells from using folic acid to create DNA, has potential in treating various solid tumors. Studies indicate that pemetrexed can work against bladder cancer and other solid tumors, but it generally has a low success rate, with only about 5% of patients responding well. However, patients with specific genetic changes in the MLL4 protein or KDM6A gene might find pemetrexed more effective. These genetic changes appear in a significant number of cancers, suggesting that patients with these mutations might respond better to the treatment. While research continues, this trial will evaluate pemetrexed as a possible new option for some patients with advanced bladder cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Devalingam Mahalingam, MBBChBAO

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

This trial is for patients with metastatic urothelial bladder cancer and other solid tumors that have spread, who also have specific genetic mutations (loss of function in MLL4-protein/KMT2D-gene or UTX-protein/KDM6A-gene or MTAP enzyme). Details on inclusion and exclusion criteria are not provided.

Inclusion Criteria

Patients of child-bearing potential and their partners must agree to adequate contraception

Patients must be able to understand and sign a written informed consent

Patients must have the ability to comply with supplemental therapies

Exclusion Criteria

Patients with uncontrolled intercurrent illnesses

Patients who received specified treatments/procedures within minimum intervals before study drug

Patients receiving other investigational agents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive pemetrexed intravenously over 10 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

21 days per cycle

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 3 months for up to 12 months.

12 months

4 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Pemetrexed

Trial Overview The trial is testing the effectiveness of Pemetrexed, a medication that inhibits tumor cells from using folic acid to create DNA, potentially killing them. It's aimed at improving treatment response in patients with certain genetic alterations.

How Is the Trial Designed?

Group I: Treatment (pemetrexed) Experimental Treatment 3 Interventions

Patients receive pemetrexed IV over 10 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood and urine sample collection on study as well as CT throughout the trial.

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

Approved in United States as Alimta for:

• Malignant pleural mesothelioma
• Non-small cell lung cancer

Approved in European Union as Alimta for:

• Malignant pleural mesothelioma
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Pemetrexed is a multitargeted antifolate that has demonstrated effectiveness against various solid tumors, including those in the genitourinary tract.

It shows promising results when used in combination with other chemotherapy agents like gemcitabine, suggesting potential for further research in advanced and adjuvant treatment settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief communication: use of the multitargeted antifolate pemetrexed (Alimta) in genitourinary cancer. Misset, JL.[2022]

Pemetrexed is an FDA-approved anti-folate agent used to treat malignant pleural mesothelioma and previously treated non-small cell lung cancer, showing efficacy in these patient populations.

In clinical trials, rash occurred in 17-22% of patients treated with pemetrexed, and this report highlights a specific case of rash due to urticarial vasculitis, contributing to the understanding of pemetrexed's side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed-associated urticarial vasculitis. Lopes, G., Vincek, V., Raez, LE.[2015]

Pemetrexed disodium (Alimta) was the first drug approved by the US FDA in February 2004 for treating malignant pleural mesothelioma, a rare cancer, highlighting its significance in oncology.

In August 2004, pemetrexed also received accelerated approval for use as a second-line treatment for non-small-cell lung cancer, demonstrating its efficacy in targeting folate-dependent processes crucial for cancer cell growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed disodium. Gibbs, D., Jackman, A.[2019]

In a phase 2 trial involving 46 patients with advanced urothelial cancer, the combination of pemetrexed and gemcitabine showed moderate antitumor activity, achieving an overall response rate of 31.8%.

While the treatment resulted in a median overall survival of 13.4 months, it also caused significant side effects, with 75% of patients experiencing severe neutropenia and 11% developing febrile neutropenia, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 trial of pemetrexed disodium and gemcitabine in advanced urothelial cancer (E4802): a trial of the Eastern Cooperative Oncology Group. Dreicer, R., Li, H., Cooney, MM., et al.[2022]

Pemetrexed is a multitargeted antifolate that effectively inhibits key enzymes involved in cancer cell growth and is active against various solid tumors, including non-small-cell lung cancer and ovarian cancer.

A recent randomized trial found that administering pemetrexed followed by gemcitabine on specific days every 21 days resulted in the best efficacy and lowest toxicity, highlighting an optimized treatment sequence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical studies of pemetrexed and gemcitabine combinations. Adjei, AA.[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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

In a study of 29 non-small-cell lung cancer patients treated with pemetrexed, 21% developed acute kidney injury (AKI) despite having an initial eGFR above the recommended threshold of 45 mL/min, indicating potential renal toxicity even in patients considered safe for treatment.

Patients with a baseline eGFR below 60 mL/min were more likely to experience AKI, suggesting that careful monitoring and management of renal function and risk factors are essential when administering pemetrexed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed induced acute kidney injury in patients with non-small cell lung cancer: reversible and chronic renal damage. Rombolà, G., Vaira, F., Trezzi, M., et al.[2021]

Pemetrexed, a treatment for malignant pleural mesothelioma and non-small cell lung cancer, has been associated with a new toxicity resembling scleroderma, as seen in two cases involving painful induration and edema of the lower extremities.

This adverse effect can be mistaken for erysipelas due to similar symptoms, but it lacks fever; recognizing this toxicity is crucial for timely diagnosis and management, and folate and vitamin B12 supplementation may help reduce its incidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pemetrexed-induced scleroderma-like changes in the lower legs]. Corbaux, C., Marie, J., Meraud, JP., et al.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4425381/

The Safety and Efficacy of Single-Agent Pemetrexed in ... The results show that although well-tolerated, pemetrexed had limited efficacy, with an objective response rate of 5% and median progression-free survival of ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S009377540270050X

Pemetrexed in bladder, head and neck, and cervical cancers Pemetrexed is a novel multitargeted antifolate analog. The drug has shown encouraging activity in a wide range of solid tumors, including cervix, ...

3. journal.waocp.org journal.waocp.org/article_30997_f53f3e04686d22504cc6147c6229e86e.pdf

RESEARCH ARTICLE Pemetrexed in Treating Patients with ... Our current study evaluated the efficacy and safety of pemetrexed based regimens on response and safety for patients with metastatic bladder cancer. Our results.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06630416?term=PEMFEXY&viewType=Table&rank=8

Study Details | NCT06630416 | Pemetrexed Response in ... This phase II trial tests how well pemetrexed works in treating patients with urothelial bladder cancer and other solid tumors that have spread from where ...

5. bcan.org bcan.org/clinicaltrials/pemetrexed-response-in-relation-to-tumor-alterations-of-gene-status-for-the-treatment-of-patients-with-metastatic-urothelial-bladder-cancer-and-other-solid-tumors/

Pemetrexed Response in Relation to Tumor Alterations of ... This phase II trial tests how well pemetrexed works in treating patients with urothelial bladder cancer and other solid tumors that have spread.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03193788?term=AREA%5BConditionSearch%5D(%22Transitional%20Cell%20Carcinoma%22)%20AND%20AREA%5BInterventionSearch%5D(%22antiemetics%22)&rank=2

Pemetrexed Maintenance in Patients With Urothelial ... This study aims to verify superiority of pemetrexed maintenance to observation for patient without disease progression after 1 st line cisplatin-based ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25845990/

The safety and efficacy of single-agent pemetrexed in ... Results: One hundred and twenty-nine patients were treated with pemetrexed. The objective response rate was 5% (95% confidence interval: 1%-9%), and the median ...