Riluzole + Sorafenib for Melanoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Warfarin, CYP3A4 modulators

Disqualifiers: HIV, Hepatitis B/C, Cardiac disease, others

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

Compensation: Varies

Number of Visits: 2

Duration: 28 days per course

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of drugs, riluzole (also known as Rilutek, Tiglutik, Exservan, Glentek, or Riluzol) and sorafenib (specifically Sorafenib Tosylate), to determine if they can jointly stop or slow the growth of melanoma and other hard-to-treat, metastatic solid tumors. Researchers aim to identify the safest and most effective dose of these drugs when used together. Suitable participants have solid tumors that do not respond to standard treatments or opt out of them. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but if you are on medications that affect certain liver enzymes (CYP3A4, CYP2B6, CYP2C8), the principal investigator will review your case. They may try to switch you to other medications if possible.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of riluzole and sorafenib tosylate is generally safe and well-tolerated. One study found this combination safe for patients with advanced solid tumors. Although specific safety data for this combination is limited, sorafenib alone is known to be safe for humans, suggesting that serious side effects are uncommon. Patients have generally shown some positive response to the treatment, indicating potential benefits. As this is a phase 1 trial, the main goal is to ensure safety and determine the best dose, so researchers will closely monitor for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of riluzole and sorafenib for treating melanoma because it targets the disease in a novel way. Unlike traditional treatments like immunotherapy or targeted therapies that focus on specific genetic mutations, riluzole works by interfering with glutamate signaling, which may help slow down the growth of melanoma cells. Sorafenib, on the other hand, inhibits multiple kinases involved in tumor growth and blood vessel formation. This dual approach may offer a more comprehensive way to tackle melanoma, potentially leading to improved outcomes for patients.

What evidence suggests that this treatment might be an effective treatment for melanoma?

This trial will evaluate the combination of riluzole and sorafenib tosylate for melanoma. Studies have shown that using these drugs together can be safe and manageable for patients with advanced solid tumors, such as melanoma. Riluzole may slow tumor growth, while sorafenib tosylate blocks enzymes that tumors need to grow. Together, these drugs aim to kill more tumor cells than when used separately. Previous research has shown that combinations with sorafenib can improve progression-free survival, meaning the disease remains stable for a longer period, in melanoma patients. These findings suggest that this drug combination could effectively treat melanoma by stopping tumor growth. ^{1 2 3 4 6}

Who Is on the Research Team?

Janice M. Mehnert

Principal Investigator

Rutgers Cancer Institute of New Jersey

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors or melanoma that's spread and can't be cured or controlled. They must have proper liver, kidney, and blood function, no serious wounds or infections, and not be on certain drugs affecting the liver enzymes. Pregnant women can't join; participants must use birth control.

Inclusion Criteria

My brain lesions were treated, I'm stable for 4 weeks, not on steroids or certain seizure meds.

Your kidney function, as measured by creatinine levels, is normal or only slightly elevated.

You have enough infection-fighting white blood cells in your body.

Exclusion Criteria

I haven't had any major abdominal issues like a fistula, perforation, or abscess in the last 6 months.

I need medication for irregular heartbeats.

I have not had a serious lung bleeding event in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive riluzole orally twice daily and sorafenib tosylate once or twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per course

Visits on days 2, 8, 10, and 15 of each course

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with assessments including changes in BCL-2, BIM, and MCL-1 expression, and microvesicle quantification.

2-3 years

What Are the Treatments Tested in This Trial?

Interventions

• Laboratory Biomarker Analysis
• Pharmacological Study
• Riluzole
• Sorafenib Tosylate

Trial Overview

The trial tests combining Riluzole with Sorafenib Tosylate to see if they're more effective together against tumor growth in patients with advanced cancer. It aims to find the safest dose of Sorafenib when used with Riluzole by monitoring how patients' bodies respond.

How Is the Trial Designed?

Group I: Treatment (riluzole and sorafenib tosylate) Experimental Treatment 4 Interventions

Patients receive riluzole PO BID and sorafenib tosylate PO QD or BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Rilutek for:

• Amyotrophic lateral sclerosis (ALS)

Approved in European Union as Riluzole for:

• Amyotrophic lateral sclerosis (ALS)

Approved in United States as Tiglutik for:

• Amyotrophic lateral sclerosis (ALS)

Approved in United States as Exservan for:

• Amyotrophic lateral sclerosis (ALS)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a safety study involving 75 patients with BRAFV600 mutation-positive metastatic melanoma, vemurafenib demonstrated an objective response rate of 46%, with a median progression-free survival of 7.4 months, indicating its efficacy in treating this aggressive cancer.

The safety profile was consistent with previous studies, with 97.3% of patients experiencing adverse events, primarily skin-related issues, and nearly half reporting severe toxicity (grade 3-5), highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The outcomes of Polish patients with advanced BRAF-positive melanoma treated with vemurafenib in a safety clinical trial. Rutkowski, P., Kozak, K., Mackiewicz, J., et al.[2020]

Dabrafenib plus trametinib has been approved for treating non-small cell lung cancer (NSCLC) with the BRAF V600E mutation, showing a response rate of approximately 65% and a median progression-free survival of 10-11 months based on clinical trials.

While the combination therapy has a manageable safety profile, it presents unique toxicities such as pyrexia, fatigue, and nausea, which may be unfamiliar to oncologists treating lung cancer, but can be effectively managed using strategies developed from experience in melanoma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Event Management in Patients with BRAF V600E-Mutant Non-Small Cell Lung Cancer Treated with Dabrafenib plus Trametinib. Chalmers, A., Cannon, L., Akerley, W.[2020]

Sorafenib is a well-tolerated multi-kinase inhibitor that targets several pathways involved in tumor growth, showing mild to moderate side effects like skin issues, diarrhea, and fatigue.

While sorafenib has limited effectiveness as a standalone treatment for melanoma, combining it with dacarbazine has shown promising results in increasing response rates and progression-free survival, although these findings need further validation in larger Phase III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sorafenib in melanoma. Mangana, J., Levesque, MP., Karpova, MB., et al.[2020]

Darovasertib, a new oral inhibitor of protein kinase C (PKC), has received orphan drug designation for treating uveal melanoma, a cancer with a high risk of metastasis and poor prognosis.

In clinical trials, darovasertib has shown greater potency and a better safety profile compared to other PKC inhibitors, and when combined with MEK inhibitors, it produces a synergistic effect, enhancing its potential efficacy in treating uveal melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darovasertib, a novel treatment for metastatic uveal melanoma. Cao, L., Chen, S., Sun, R., et al.[2023]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01303341

Riluzole and Sorafenib Tosylate in Treating Patients With ...

This phase I trial studies the side effects and best dose of sorafenib tosylate when given together with riluzole in treating patients with solid tumors or ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10085060/

A phase I trial of riluzole and sorafenib in patients with ...

Conclusion: Combination therapy with riluzole and sorafenib was safe and tolerable in patients with advanced solid tumors. The partial response ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3885142/

Metastatic melanoma – a review of current and future drugs

However, sorafenib in combination with dacarbazine resulted in a significant improvement in PFS in patients with advanced melanoma [96]. Additionally, ...

4.

withpower.com

withpower.com/trial/phase-1-neoplasms-1-2011-815ea

Riluzole + Sorafenib for Melanoma · Info for Participants

Riluzole may slow tumor growth, and sorafenib tosylate blocks processes needed for tumor growth. The combination aims to kill more tumor cells. Show more. Will ...

5.

aging.networkofcare.org

aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT01303341?keyword=%22Stage%20III%20Cutaneous%20Melanoma%22

Riluzole and Sorafenib Tosylate in Treating Patients ...

Riluzole may stop or slow the growth of tumor cells. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell ...

6.

sciensage.info

sciensage.info/index.php/JASR/article/download/2410/1692

Deciphering Riluzole: Illuminating Unexplored Avenues in ...

Additionally, radiation therapy is more effective against glioma and melanoma with riluzole pretreatment. In combination with chemotherapeutic ...