27 Participants Needed

Trametinib + Ceritinib for Melanoma

Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. Specifically, you must stop medications that affect the heart's rhythm, certain enzyme-affecting drugs, warfarin, unstable doses of corticosteroids, and some anticonvulsants at least one week before starting the trial.

What data supports the effectiveness of the drug combination Trametinib and Ceritinib for treating melanoma?

Research shows that combining Trametinib with Ceritinib can effectively inhibit tumor growth in certain types of melanoma that lack common mutations, by targeting specific cellular pathways. Additionally, Trametinib has been shown to improve survival in melanoma patients when used with other drugs.12345

What safety information is available for Trametinib in combination therapies?

Trametinib, when used in combination with other drugs like dabrafenib, has been shown to have a manageable safety profile, though it can cause side effects such as fever, fatigue, and nausea. These side effects have been effectively managed in patients with melanoma, suggesting that the combination can be safe with proper monitoring and management.12678

How is the drug combination of Trametinib and Ceritinib unique for treating melanoma?

Trametinib is a MEK inhibitor that targets a specific pathway in melanoma cells, often used in combination with other drugs like dabrafenib to improve effectiveness and delay resistance. The combination with Ceritinib, which is typically used for lung cancer, may offer a novel approach by targeting different pathways, potentially enhancing treatment efficacy for melanoma.127910

What is the purpose of this trial?

The main purpose of this study is to determine the risks and benefits of ceritinib (ZYKADIA) given in combination with trametinib (MEKINIST) in patients who have progressed on prior melanoma therapy.

Research Team

ZE

Zeynep Eroglu, M.D.

Principal Investigator

H. Lee Moffitt Cancer Center and Research Institute

Eligibility Criteria

This trial is for adults with advanced melanoma that can't be surgically removed and who have already tried certain therapies without success. They must be in relatively good health, able to use birth control, and have tumors measurable by standard criteria. People with severe allergies to the drugs' ingredients, uncontrolled brain metastases, recent heart issues, or those on conflicting medications are excluded.

Inclusion Criteria

My last cancer treatment did not include BRAF/MEK inhibitors.
I agree to use effective birth control during and for 90 days after the study.
I have had radiation treatment before.
See 7 more

Exclusion Criteria

I have stable brain metastases not needing steroids, or no brain metastases.
I have had cancer before, but it's under control and I'm not currently on cancer treatment.
I am on medication that cannot be stopped for the study, including those affecting heart rhythm or requiring careful monitoring.
See 5 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive trametinib and ceritinib in 4-week cycles

12 months
Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years
Every 3 months for the first year, then every 6 months

Treatment Details

Interventions

  • Ceritinib
  • Trametinib
Trial Overview The study tests a combination of two drugs: Trametinib and Ceritinib. It aims to see if this combo is effective for patients whose melanoma has worsened despite previous treatments including PD1/PD-L1 inhibitors (and BRAF/MEK inhibitors if they have a specific mutation).
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Trametinib + Ceritinib TreatmentExperimental Treatment2 Interventions
Study treatment will be given in cycles. Each cycle will be 4 weeks (28 days). Post-Treatment (follow-up) Period: Participants will return to the study site between 30-40 days after the last dose of trametinib + ceritinib for an end-of-treatment assessment. Additional follow-up will occur for related Adverse Events (AEs) that are not resolved by this time and related Serious Adverse Events (SAEs) that occur after the time of this visit. Participants will be followed for survival every 3 months for the first year following end of treatment, and then every 6 months for up to 5 years after end of treatment.

Ceritinib is already approved in United States for the following indications:

🇺🇸
Approved in United States as Danyelza for:
  • High-risk neuroblastoma in the bone or bone marrow

Find a Clinic Near You

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials
576
Recruited
145,000+

Novartis Pharmaceuticals

Industry Sponsor

Trials
2,963
Recruited
4,275,000+
Founded
1996
Headquarters
Basel, Switzerland
Known For
Precision medicine
Top Products
Gleevec, Cosentyx, Entresto, Kisqali
Dr. Vas Narasimhan profile image

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye profile image

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

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 phase III study involving patients with BRAF V600 mutation-positive melanoma, trametinib significantly improved quality of life (QOL) compared to chemotherapy, with patients reporting better global health status and less functional impairment.
Patients treated with trametinib experienced improvements in symptoms like pain and insomnia, while chemotherapy led to worsening symptoms and a decline in overall health, highlighting trametinib's potential as a more tolerable treatment option.
Functional and symptom impact of trametinib versus chemotherapy in BRAF V600E advanced or metastatic melanoma: quality-of-life analyses of the METRIC study.Schadendorf, D., Amonkar, MM., Milhem, M., et al.[2023]
The study found that the combination of encorafenib and trametinib showed the highest anti-tumor activity, effectively suppressing cell proliferation and inducing apoptosis in both BRAF and NRAS mutant melanoma cells.
Encouragingly, this combination also delayed the development of resistance more effectively than currently approved treatments, suggesting it could lead to better outcomes for patients with melanoma.
Head-to-Head Comparison of BRAF/MEK Inhibitor Combinations Proposes Superiority of Encorafenib Plus Trametinib in Melanoma.Schulz, A., Raetz, J., Karitzky, PC., et al.[2022]

References

Combined therapy with dabrafenib and trametinib in BRAF-mutated metastatic melanoma in a real-life setting: the INT Milan experience. [2017]
Functional and symptom impact of trametinib versus chemotherapy in BRAF V600E advanced or metastatic melanoma: quality-of-life analyses of the METRIC study. [2023]
Ceritinib Enhances the Efficacy of Trametinib in BRAF/NRAS-Wild-Type Melanoma Cell Lines. [2020]
Head-to-Head Comparison of BRAF/MEK Inhibitor Combinations Proposes Superiority of Encorafenib Plus Trametinib in Melanoma. [2022]
Concurrent MEK2 mutation and BRAF amplification confer resistance to BRAF and MEK inhibitors in melanoma. [2022]
Adverse Event Management in Patients with BRAF V600E-Mutant Non-Small Cell Lung Cancer Treated with Dabrafenib plus Trametinib. [2020]
Open-label, phase IIa study of dabrafenib plus trametinib in East Asian patients with advanced BRAF V600-mutant cutaneous melanoma. [2020]
Management of Treatment-Related Adverse Events with Agents Targeting the MAPK Pathway in Patients with Metastatic Melanoma. [2019]
Trametinib in metastatic melanoma. [2016]
BRAFi/MEKi in patients with metastatic melanoma: predictive factors of complete response. [2019]
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