Meclofenamate for Brain Cancer

Not currently recruiting at 7 trial locations

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Antiplatelets, Anticoagulants

Disqualifiers: Progressive systemic disease, Leptomeningeal metastases, Primary brain tumor, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore whether meclofenamate, a drug previously used for pain relief, can slow or prevent the growth of brain metastasis (cancer that has spread to the brain). Researchers seek to determine the feasibility of a larger study and observe the drug's effects on brain metastasis and the digestive system. Suitable participants have at least one brain metastasis that has not been recently treated with surgery or radiation. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to new treatment options for brain metastasis.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on anti-platelet or anti-coagulation therapy. It's best to discuss your specific medications with the trial team.

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

Research has shown that meclofenamate has been safely used in the past to treat pain, suggesting it might be safe for other uses. Studies have found that in lab tests, meclofenamate can slow the growth of brain tumors. While this is encouraging, this study marks the first time it is being tested for this specific use in patients.

Earlier research indicated that most patients tolerated meclofenamate well, experiencing no serious side effects. However, like any medication, some side effects can occur. Since this study focuses on brain tumors, researchers will carefully monitor for any new or unexpected effects.

This study serves as a small test to determine if a larger study is worthwhile. It will help researchers understand how the drug affects brain tumors and any possible effects on the digestive system. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for brain cancer, which typically involve surgery, radiation, and chemotherapy, meclofenamate is an oral medication that offers a different approach. This drug is known as a nonsteroidal anti-inflammatory drug (NSAID) and has a unique potential to reduce inflammation and possibly inhibit tumor growth. Researchers are excited about meclofenamate because it targets cancer cells in a novel way, focusing on the inflammation pathways that other treatments do not specifically address. This could make it a valuable addition to existing therapies, possibly enhancing their effectiveness and offering new hope for patients with brain cancer.

What evidence suggests that meclofenamate might be an effective treatment for brain metastasis?

Research has shown that meclofenamate can slow the growth of brain tumors in lab studies. It has also been tested on other brain cancers, such as glioblastoma, affecting how cancer cells adhere and communicate. Originally used for pain relief, researchers are now exploring its potential to halt new cancer growth in the brain. Although human studies on brain tumors are limited, these early results suggest it might help control the disease. In this trial, all enrolled patients will receive the study drug, meclofenamate, at 100 mg PO BID. ^{1 3 4 6 7}

Who Is on the Research Team?

Adrienne Boire, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cance Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with recurrent or progressive brain metastasis from solid tumors, visible on MRI. Participants must have a stable systemic disease or no evidence of disease and can't be pregnant, have had recent surgery, active bleeding issues, severe allergies to NSAIDs like meclofenamate, certain heart conditions, uncontrolled systemic cancer growth, or poor kidney/liver function.

Inclusion Criteria

Systemic disease must be well-controlled or NED in the opinion of the patient's primary oncologist

I may have multiple brain metastases.

I have had surgery or SRS for some, but not all, of my recurrent cancer lesions.

Exclusion Criteria

Platelet count ≤ 70,000/mm3

International normalized ratio (INR) > 1.6 and a Partial Thromboplastin Time (PTT) > 40 seconds

AST or ALT > 200 U/L

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive meclofenamate at 100 mg PO BID to prevent new brain metastasis

2 months

Regular visits for monitoring and MRI evaluations

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Periodic visits for adverse event monitoring and progression-free survival assessment

What Are the Treatments Tested in This Trial?

Interventions

• Meclofenamate

Trial Overview The study tests Meclofenamate's effectiveness in preventing new brain metastases in patients whose cancer has spread to the brain. It's a pilot study aimed at seeing if larger trials are feasible and understanding the drug's impact on both the patient and their brain metastasis.

How Is the Trial Designed?

Group I: Meclofenamate Experimental Treatment 1 Intervention

All enrolled patients will receive the study drug, meclofenamate at 100 mg PO BID.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

Temodar is a promising new drug for treating brain tumors and other cancers, currently being researched for its effectiveness against solid tumors, glioblastoma multiforme, and metastatic melanoma.

It offers adult patients with anaplastic astrocytoma a convenient treatment option with minimal side effects, providing hope for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temodar offers promise for treating astrocytomas. Armstrong, T., Hancock, C.[2018]

In a phase II trial involving 88 patients with recurrent glioblastoma, the addition of mebendazole (MBZ) to either temozolomide (TMZ) or lomustine (CCNU) did not improve overall survival (OS) beyond the pre-set benchmark of 55% at 9 months, with OS rates of 36.6% and 45% for the TMZ-MBZ and CCNU-MBZ arms, respectively.

The study found that while MBZ was well tolerated, with no treatment-related deaths, a significant portion of patients had poor performance status, which likely impacted the overall survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mebendazole plus lomustine or temozolomide in patients with recurrent glioblastoma: A randomised open-label phase II trial. Patil, VM., Menon, N., Chatterjee, A., et al.[2022]

The combination of ranimustine (MCNU) and recombinant human mutant TNF-alpha (TNF-SAM2) was found to be safe and well-tolerated in 26 patients with newly diagnosed malignant astrocytomas, with no severe or life-threatening toxicities reported.

While the treatment showed promising results in patients with anaplastic astrocytoma, leading to a median survival time of 330 weeks, it did not demonstrate improved efficacy in glioblastoma patients compared to historical controls receiving MCNU alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant mutant human tumor necrosis factor-alpha (TNF-SAM2) immunotherapy with ranimustine chemotherapy and concurrent radiation therapy for malignant astrocytomas. Fukushima, T., Yamamoto, M., Oshiro, S., et al.[2012]

In a phase I study involving 12 patients with newly diagnosed glioblastoma, dimethyl fumarate (DMF) was safely combined with standard treatments of radiotherapy and temozolomide, with no dose-limiting toxicities observed.

The recommended phase 2 dose (RP2D) for DMF was established at 240 mg three times daily, and the median progression-free survival was 8.7 months, with a median overall survival of 13.8 months, indicating potential efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of dimethyl fumarate, temozolomide, and radiation therapy in glioblastoma. Shafer, D., Tombes, MB., Shrader, E., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8767701/

Phase I/II trial of meclofenamate in progressive MGMT ... Phase I/II trial of meclofenamate in progressive MGMT-methylated glioblastoma under temozolomide second-line therapy—the MecMeth/NOA-24 trial.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35045869/

Phase I/II trial of meclofenamate in progressive MGMT ... This study is set up to assess toxicity and first indications of efficacy of MFA repurposed in the setting of a very difficult-to-treat recurrent tumor.

3. clinicaltrials.eu clinicaltrials.eu/trial/study-of-meclofenamate-sodium-and-temozolomide-for-patients-with-progressive-mgmt-methylated-glioblastoma/

Study of Meclofenamate Sodium and Temozolomide for ... Meclofenamate Sodium is being tested in this trial to see if it can help treat a type of brain cancer called glioblastoma. Researchers want to find out if ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02429570

Study Details | NCT02429570 | Meclofenamate in Subjects ... Meclofenamate is a drug which has been shown to reduce brain metastasis growth in the laboratory. This medicine has been used in the past to treat pain.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8563322/

Meclofenamate causes loss of cellular tethering and ... Meclofenamate causes loss of cellular tethering and decoupling of functional networks in glioblastoma.

6. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-021-05977-0

Phase I/II trial of meclofenamate in progressive MGMT ... It will review safety data and recruitment data. It will also provide a recommendation for the further proceeding of the trial to the ...

7. withpower.com withpower.com/trial/phase-brain-neoplasms-3-2015-37932

Meclofenamate for Brain Cancer · Info for Participants The combination of ranimustine (MCNU) and recombinant human mutant TNF-alpha (TNF-SAM2) was found to be safe and well-tolerated in 26 patients with newly ...