Meclofenamate for Brain Cancer

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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Cancer that has spread to the brain, or brain metastasis, is difficult to treat. 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. But, in this study, it will be used to prevent new brain metastasis. This is the first time that meclofenamate will be used in patients with brain metastasis. This is a pilot study which means that the purpose of this study is to determine if a larger clinical trial of meclofenamate is possible in patients with brain metastasis. This study also aims to find out what effects, good and/or bad meclofenamate has on the patient and the cancer that has spread to the brain. The investigators also want to learn more about potential effects that this drug may have in the digestive system.

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.

What data supports the effectiveness of the drug Meclofenamate for brain cancer?

Preclinical research suggests that Meclofenamate, originally an anti-inflammatory drug, can make glioblastoma cells more sensitive to the chemotherapy drug temozolomide by disrupting certain cell communication pathways and structures within the tumor. ^{1 2 3 4 5}

How does the drug Meclofenamate differ from other treatments for brain cancer?

Meclofenamate is unique because it was originally developed as a nonsteroidal anti-inflammatory drug (NSAID) and has shown potential in making glioblastoma cells more sensitive to temozolomide, a common chemotherapy drug, by disrupting the tumor's cellular communication and structure. ^{1 2 3 6 7}

Research Team

Adrienne Boire, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cance Center

Eligibility Criteria

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

I may have multiple brain metastases.

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

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

Exclusion Criteria

My cancer has spread to the lining of my brain and spinal cord.

Platelet count ≤ 70,000/mm3

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

References

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

Phase I/II trial of meclofenamate in progressive MGMT-methylated glioblastoma under temozolomide second-line therapy-the MecMeth/NOA-24 trial. [2022]

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

Phase I trial of dimethyl fumarate, temozolomide, and radiation therapy in glioblastoma. [2022]

3. Greece 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. [2012]

4. England pubmed.ncbi.nlm.nih.gov

A phase 1b randomised, placebo-controlled trial of nabiximols cannabinoid oromucosal spray with temozolomide in patients with recurrent glioblastoma. [2022]

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

Neurocognitive functioning and quality of life in patients with recurrent malignant gliomas treated on a phase Ib trial evaluating topotecan by convection-enhanced delivery. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Mebendazole plus lomustine or temozolomide in patients with recurrent glioblastoma: A randomised open-label phase II trial. [2022]

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

Temodar offers promise for treating astrocytomas. [2018]