52 Participants Needed

Drug Combinations for Advanced Melanoma

HA
Overseen ByHussein A Tawbi
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on certain treatments like corticosteroids or immunosuppressive medications, you may need to adjust or stop them before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Dabrafenib and Trametinib for advanced melanoma?

Research shows that the combination of Dabrafenib and Trametinib is more effective and safer than using a BRAF inhibitor alone for treating metastatic melanoma, leading to improved survival rates and better outcomes for patients with BRAF mutations.12345

Is the combination of dabrafenib and trametinib safe for humans?

The combination of dabrafenib and trametinib is generally considered safe, with most patients experiencing mild to moderate side effects that can be managed with dose adjustments. However, some serious side effects like heart issues and high fever can occur, so it's important to monitor and manage these during treatment.25678

How is the drug combination of Dabrafenib, Encorafenib, Nivolumab, and Trametinib unique for treating advanced melanoma?

This drug combination is unique because it combines BRAF and MEK inhibitors (Dabrafenib, Encorafenib, and Trametinib) with an immune checkpoint inhibitor (Nivolumab), potentially addressing both tumor growth and immune system activation, which may improve outcomes in patients with advanced melanoma.49101112

What is the purpose of this trial?

This phase II trial studies the side effects and how well nivolumab with trametinib and dabrafenib, or encorafenib and binimetinib work in treating patients with BRAF-mutated stage III-IV melanoma that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as nivolumab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Trametinib, dabrafenib, encorafenib, and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known if nivolumab with trametinib and dabrafenib, or encorafenib and binimetinib may work better in treating patients with BRAF-mutated melanoma.

Research Team

Hussein A. Tawbi | MD Anderson Cancer ...

Hussein A. Tawbi

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with stage III-IV melanoma that's spread or can't be surgically removed, specifically those with a BRAF V600 mutation. It includes patients who've had prior treatments except for BRAFi/MEKi and requires stable brain metastases if present. Participants must have good organ function, not need high steroid doses, and agree to contraception.

Inclusion Criteria

I've had treatments for melanoma but not with BRAFi or MEKi. Any side effects from previous treatments are minimal.
Your hemoglobin level is higher than 9.0 grams per deciliter within one week before you join the study.
Your liver enzymes (AST/ALT) should not be more than three times the normal level.
See 13 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive nivolumab, dabrafenib, and trametinib or encorafenib and binimetinib in cycles of 28 days for up to 3 years

Up to 3 years
Every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

3 years
30 days post-treatment, then every 3 months

Treatment Details

Interventions

  • Dabrafenib
  • Encorafenib
  • Laboratory Biomarker Analysis
  • Nivolumab
  • Pharmacological Study
  • Trametinib
Trial Overview The study tests how well nivolumab (an immunotherapy drug) works with trametinib and dabrafenib or encorafenib and binimetinib (targeted therapies) in treating advanced melanoma. The goal is to see which combination better inhibits tumor growth by blocking enzymes needed for cell growth.
Participant Groups
3Treatment groups
Experimental Treatment
Group I: Arm C (NEB)Experimental Treatment5 Interventions
Patients receive nivolumab IV over 30 minutes on day 1 and 15, encorafenib PO QD on days 1-28, and binimetinib PO BID on days 1-28. Cycles repeats every 28 days for up to 3 years in the absence of disease progression or unacceptable toxicity.
Group II: Arm B (NT, closed to accrual)Experimental Treatment4 Interventions
Patients receive nivolumab IV over 30 minutes on day 1 and 15, and trametinib PO QD on days 1-28. Cycles repeats every 28 days for up to 3 years in the absence of disease progression or unacceptable toxicity.
Group III: Arm A (NDT, CLOSED)Experimental Treatment5 Interventions
Patients receive nivolumab IV over 30 minutes on day 1, dabrafenib PO BID on days 1-28, and trametinib PO QD on days 1-28. Cycles repeats every 28 days for up to 3 years in the absence of disease progression or unacceptable toxicity.

Dabrafenib is already approved in European Union, United States, Canada, Japan for the following indications:

🇪🇺
Approved in European Union as Tafinlar for:
  • Unresectable or metastatic melanoma with a BRAF V600 mutation
  • Adjuvant treatment of melanoma with a BRAF V600 mutation
🇺🇸
Approved in United States as Tafinlar for:
  • Unresectable or metastatic melanoma with a BRAF V600E mutation
  • Adjuvant treatment of melanoma with a BRAF V600E or V600K mutation
  • Metastatic non-small cell lung cancer with a BRAF V600E mutation
🇨🇦
Approved in Canada as Tafinlar for:
  • Unresectable or metastatic melanoma with a BRAF V600 mutation
  • Adjuvant treatment of melanoma with a BRAF V600 mutation
🇯🇵
Approved in Japan as Tafinlar for:
  • Unresectable or metastatic melanoma with a BRAF V600 mutation

Find a Clinic Near You

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials
3,107
Recruited
1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Findings from Research

Combination therapy with dabrafenib and trametinib for BRAF-mutated metastatic melanoma showed a high overall response rate, with 64.6% of patients achieving a partial response and 6.2% achieving a complete response, indicating its efficacy in treating this condition.
The treatment was found to be relatively safe, with only 8.3% of patients experiencing severe adverse events, and 62.5% of patients remained on treatment, suggesting good tolerability in a real-life clinical setting.
Combined therapy with dabrafenib and trametinib in BRAF-mutated metastatic melanoma in a real-life setting: the INT Milan experience.Cavalieri, S., Di Guardo, L., Cimminiello, C., et al.[2017]
In a study of 78 BRAF inhibitor-naive patients with BRAF V600 mutation-positive metastatic melanoma treated with dabrafenib and trametinib, the median overall survival was over 2 years, with 72% of patients alive at 1 year and 47% at 3 years.
Approximately 20% of patients were progression-free at 3 years, with better outcomes associated with having fewer than three organ metastases and lower baseline lactate dehydrogenase levels, suggesting these factors may help predict durable responses.
Overall Survival and Durable Responses in Patients With BRAF V600-Mutant Metastatic Melanoma Receiving Dabrafenib Combined With Trametinib.Long, GV., Weber, JS., Infante, JR., et al.[2022]
In a study of 66 patients with metastatic BRAF-mutated melanoma treated with dabrafenib and trametinib, 15 patients achieved a complete response (CR), indicating a significant survival benefit from this treatment.
The likelihood of achieving a complete response was higher in patients with smaller lesions (39.3% CR rate) compared to those with larger lesions (10.5% CR rate), suggesting that lesion size and the number of metastatic sites are important factors in treatment outcomes.
BRAFi/MEKi in patients with metastatic melanoma: predictive factors of complete response.Ribero, S., Malavenda, O., Fava, P., et al.[2019]

References

Combined therapy with dabrafenib and trametinib in BRAF-mutated metastatic melanoma in a real-life setting: the INT Milan experience. [2017]
Overall Survival and Durable Responses in Patients With BRAF V600-Mutant Metastatic Melanoma Receiving Dabrafenib Combined With Trametinib. [2022]
BRAFi/MEKi in patients with metastatic melanoma: predictive factors of complete response. [2019]
Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma. [2023]
Dabrafenib and trametinib, alone and in combination for BRAF-mutant metastatic melanoma. [2022]
Interim analysis for post-marketing surveillance of dabrafenib and trametinib combination therapy in Japanese patients with unresectable and metastatic melanoma with BRAF V600 mutation. [2022]
The safety and efficacy of dabrafenib and trametinib for the treatment of melanoma. [2017]
Trametinib (MEKINIST°) Metastatic or inoperable BRAF V600-positive melanoma: a few extra months of life. [2019]
COMBI-r: A Prospective, Non-Interventional Study of Dabrafenib Plus Trametinib in Unselected Patients with Unresectable or Metastatic BRAF V600-Mutant Melanoma. [2023]
10.United Statespubmed.ncbi.nlm.nih.gov
Economic Evaluation of Three BRAF + MEK Inhibitors for the Treatment of Advanced Unresectable Melanoma With BRAF Mutation From a US Payer Perspective. [2023]
11.United Statespubmed.ncbi.nlm.nih.gov
Clinical, Molecular, and Immune Analysis of Dabrafenib-Trametinib Combination Treatment for BRAF Inhibitor-Refractory Metastatic Melanoma: A Phase 2 Clinical Trial. [2022]
Combination dabrafenib and trametinib in the management of advanced melanoma with BRAFV600 mutations. [2018]
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