Riluzole + Sorafenib for Melanoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

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

35 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests the safety and best dose of combining riluzole and sorafenib tosylate for patients with advanced solid tumors or melanoma that don't respond to standard treatments. Riluzole may slow tumor growth, and sorafenib tosylate blocks processes needed for tumor growth. The combination aims to kill more tumor cells.

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.

What data supports the effectiveness of the drug Riluzole + Sorafenib for Melanoma?

Sorafenib has been studied in various clinical trials for melanoma, showing it can inhibit tumor growth by targeting specific proteins involved in cancer cell proliferation. It is generally well tolerated, with mild to moderate side effects. ^{1 2 3 4 5}

Is the combination of Riluzole and Sorafenib safe for humans?

Sorafenib has been tested in various clinical trials for melanoma and is generally well tolerated, with mild to moderate side effects like skin issues, diarrhea, and tiredness. There is no specific safety data available for the combination of Riluzole and Sorafenib, but Sorafenib alone has shown a manageable safety profile in humans. ^{1 2 6 7 8}

What makes the drug combination of Riluzole and Sorafenib unique for treating melanoma?

The combination of Riluzole and Sorafenib for melanoma is unique because it pairs Riluzole, a drug typically used for neurological conditions, with Sorafenib, a multi-kinase inhibitor that targets tumor growth and blood supply. This novel approach aims to enhance the effectiveness of treatment by combining different mechanisms of action, which is not common in standard melanoma therapies. ^{1 2 4 9 10}

Research Team

Janice M. Mehnert

Principal Investigator

Rutgers Cancer Institute of New Jersey

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

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

Phase II trial of sorafenib in combination with carboplatin and paclitaxel in patients with metastatic uveal melanoma: SWOG S0512. [2021]

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

Sorafenib in melanoma. [2020]

3. Australia pubmed.ncbi.nlm.nih.gov

Medical management of malignant melanoma. [2022]

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

DOC-MEK: a double-blind randomized phase II trial of docetaxel with or without selumetinib in wild-type BRAF advanced melanoma. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Darovasertib, a novel treatment for metastatic uveal melanoma. [2023]

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

Adverse Event Management in Patients with BRAF V600E-Mutant Non-Small Cell Lung Cancer Treated with Dabrafenib plus Trametinib. [2020]

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

Trametinib: A Targeted Therapy in Metastatic Melanoma. [2020]

8. Poland pubmed.ncbi.nlm.nih.gov

The outcomes of Polish patients with advanced BRAF-positive melanoma treated with vemurafenib in a safety clinical trial. [2020]

9. Germany pubmed.ncbi.nlm.nih.gov

Multiple colon ulcerations, perforation and death during treatment of malignant melanoma with sorafenib. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Sorafenib in advanced melanoma: a Phase II randomised discontinuation trial analysis. [2020]