What is the mechanism of action of this treatment?

The most common treatments for Thyroid Cancer, particularly those involving BRAF and MEK inhibition, include targeted therapies like Dabrafenib and Trametinib. These drugs work by inhibiting the BRAF V600E mutation and the MEK enzyme, respectively, which are part of the MAPK/ERK signaling pathway that promotes cancer cell growth and survival. By blocking this pathway, these treatments can reduce tumor growth and proliferation. This is particularly important for Thyroid Cancer patients with BRAF V600E mutations, as these targeted therapies can offer a more effective and personalized treatment option compared to traditional chemotherapy, potentially leading to better outcomes and fewer side effects.

What side effects are associated with this type of intervention?

The most common side effects of treatments for thyroid cancer using BRAF and MEK inhibitors like Dabrafenib and Trametinib include fatigue, pyrexia (fever), headache, and decreased neutrophil count. Other frequently observed side effects are nausea, skin rash, and increased liver function tests. These adverse events are consistent across various studies involving these drugs for different types of cancers.

What prior FDA approvals exist?

The FDA has approved the combination of dabrafenib and trametinib for the treatment of BRAF V600E mutation-positive differentiated thyroid carcinoma that is refractory to radioactive iodine and has progressed following prior VEGFR targeted therapy. This combination targets the BRAF and MEK pathways, which are crucial in the proliferation of cancer cells with BRAF mutations. Other similar treatments include single-agent BRAF inhibitors like vemurafenib, which have shown efficacy in various BRAF-mutant cancers.

What other types of research exist?

Promising novel alternatives to Dabrafenib plus Trametinib for thyroid cancer patients include selective RET inhibitors such as Selpercatinib and Pralsetinib. These agents have shown efficacy in inducing tumor shrinkage and stabilizing progressive metastatic disease in RET-mutated thyroid cancers. Additionally, other potent and selective RET inhibitors like TPX-0046 and BOS172738 are currently being tested in clinical trials and may offer new treatment options.

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Kinase Inhibitor

Dabrafenib + Trametinib for Thyroid Cancer

Phase 3

Waitlist Available

Research Sponsored by Novartis Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

BRAFV600E mutation positive tumor sample as per Novartis designated central laboratory result

Radio active iodine refractory disease

Must not have

Previous treatment with BRAF inhibitor and/or MEK inhibitor

Concomitant RET Fusion Positive Thyroid cancer

Timeline

Screening 3 weeks

Treatment Varies

Follow Up screening, week 4, week 8, week 12, week 20 and every 12 weeks after week 20, up to approximately 2 years

Awards & highlights

Pivotal Trial

Summary

This trial tests two drugs, dabrafenib and trametinib, on adults with a specific type of advanced thyroid cancer. These patients have a genetic mutation and have not responded to other treatments. The drugs work by blocking proteins that help cancer cells grow.

Who is the study for?

Adults over 18 with advanced thyroid cancer that's not responding to radioactive iodine and has a specific mutation (BRAFV600E) can join. They must have tried at least one but no more than two prior therapies targeting VEGFR, be in decent physical condition, and have at least one tumor that can be measured. People who've had certain other cancers or treatments recently, or those with eye disease risks, cannot participate.

What is being tested?

The trial is testing the effectiveness of combining Dabrafenib and Trametinib against placebos in patients whose thyroid cancer has worsened despite previous treatment. Participants will be randomly assigned to either the drug combo or placebo group in a 2:1 ratio based on their past treatments.

What are the potential side effects?

Potential side effects from Dabrafenib and Trametinib may include fever, fatigue, skin rash, headache, joint pain, nausea, vomiting; however individual experiences may vary.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My tumor has the BRAFV600E mutation.

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My thyroid cancer does not respond to radioactive iodine treatment.

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My thyroid cancer has spread and was confirmed by lab tests.

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I need assistance with daily activities due to my health condition.

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My condition worsened after 1 or 2 treatments targeting VEGFR.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have been treated with BRAF or MEK inhibitors before.

Select...

My thyroid cancer is RET fusion positive.

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I have a history or risk of eye blood vessel blockage or swelling.

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I haven't had radiation for bone metastasis in the last 2 weeks or any other radiation in the last 4 weeks.

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I haven't taken any kinase inhibitor drugs in the last 2 weeks.

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My thyroid cancer is anaplastic or medullary.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ screening, week 4, week 8, week 12, week 20 and every 12 weeks after week 20, up to approximately 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~screening, week 4, week 8, week 12, week 20 and every 12 weeks after week 20, up to approximately 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and screening, week 4, week 8, week 12, week 20 and every 12 weeks after week 20, up to approximately 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Progression Free Survival

Secondary study objectives

Duration of response

Number of participants with trametinib associated serous retinopathy ocular events

Overall Response Rate

+1 more

Side effects data

From 2021 Phase 3 trial • 552 Patients • NCT03551626

68%

Pyrexia

32%

Headache

30%

Blood creatine phosphokinase increased

27%

Diarrhoea

26%

Fatigue

26%

Chills

24%

Asthenia

23%

Nausea

21%

Arthralgia

21%

Rash

15%

Vomiting

15%

Myalgia

14%

Alanine aminotransferase increased

14%

Cough

13%

Lipase increased

13%

Aspartate aminotransferase increased

12%

Influenza like illness

12%

Oedema peripheral

Pain in extremity

Neutropenia

Abdominal pain

Constipation

Muscle spasms

Back pain

Blood alkaline phosphatase increased

Decreased appetite

Hypophosphataemia

Dyspnoea

Erythema

Hypertension

Amylase increased

Hyperglycaemia

Dry skin

Dizziness

Abdominal pain upper

Pain

Pruritus

Oropharyngeal pain

Ejection fraction decreased

Atrial fibrillation

Erysipelas

Cellulitis

Basal cell carcinoma

Pulmonary embolism

100%

80%

60%

40%

20%

Study treatment Arm

Dabrafenib+Trametinib (On-treatment)

Dabrafenib+Trametinib (Post-treatment Follow-up)

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Dabrafenib plus trametinibExperimental Treatment2 Interventions

Participants will be treated with dabrafenib twice daily and trametinib once daily

Group II: Placebo dabrafenib plus placebo trametinibPlacebo Group2 Interventions

Participants will receive placebo dabrafenib twice daily and placebo trametinib once daily

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Trametinib

2014

Completed Phase 2

~1630

Dabrafenib

2011

Completed Phase 3

~4120

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Thyroid Cancer, particularly those involving BRAF and MEK inhibition, include targeted therapies like Dabrafenib and Trametinib. These drugs work by inhibiting the BRAF V600E mutation and the MEK enzyme, respectively, which are part of the MAPK/ERK signaling pathway that promotes cancer cell growth and survival. By blocking this pathway, these treatments can reduce tumor growth and proliferation. This is particularly important for Thyroid Cancer patients with BRAF V600E mutations, as these targeted therapies can offer a more effective and personalized treatment option compared to traditional chemotherapy, potentially leading to better outcomes and fewer side effects.

Combined BRAF and MEK inhibition with PD-1 blockade immunotherapy in BRAF-mutant melanoma.Real-World Experience with Targeted Therapy for the Treatment of Anaplastic Thyroid Carcinoma.Factors predictive of response, disease progression, and overall survival after dabrafenib and trametinib combination treatment: a pooled analysis of individual patient data from randomised trials.