164 Participants Needed

Dabrafenib + Trametinib for Brain Tumors

Recruiting at 70 trial locations
NP
Overseen ByNovartis Pharmaceuticals
Age: Any Age
Sex: Any
Trial Phase: Phase 4
Sponsor: Novartis Pharmaceuticals
Must be taking: Dabrafenib, Trametinib
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

What is the purpose of this trial?

This trial is studying the effects of two cancer medications, dabrafenib and trametinib, in children. These drugs work by stopping signals that make cancer cells grow. Dabrafenib and trametinib have shown benefits in various BRAF-mutant tumors, including melanoma, lung cancer, and thyroid cancer. The goal is to see how these treatments affect children over time.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must already be receiving dabrafenib and/or trametinib treatment to participate.

What data supports the effectiveness of the drug combination Dabrafenib and Trametinib for treating brain tumors?

Research shows that the combination of Dabrafenib and Trametinib is effective in treating brain tumors with a specific mutation (BRAF V600E). It has been approved by the FDA for treating low-grade glioma in children, showing a higher response rate compared to other treatments. Additionally, it has shown positive results in treating other cancers with the same mutation, like melanoma, which often spreads to the brain.12345

Is the combination of Dabrafenib and Trametinib safe for humans?

The combination of Dabrafenib and Trametinib has been generally well tolerated in humans, with most side effects being mild or moderate and manageable. It has been used safely in patients with various types of cancer, including melanoma and brain tumors, without new safety concerns.12346

How is the drug Dabrafenib + Trametinib unique for treating brain tumors?

Dabrafenib + Trametinib is unique because it targets the BRAF V600E mutation, a common driver in some brain tumors, and has shown dramatic clinical responses and reduced skin-related side effects compared to other treatments. This combination has been effective in treating other cancers with the same mutation, like melanoma, and is now being explored for brain tumors.12478

Research Team

NP

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

This trial is for pediatric patients with various brain tumors who are already participating in Novartis-sponsored studies and receiving dabrafenib/trametinib. They must have shown compliance, be likely to benefit from continued treatment, and not have severe unresolved toxicities related to the drugs. Those previously on chemotherapy can join after switching to the experimental arm.

Inclusion Criteria

In the opinion of the investigator is likely to benefit from continued treatment
Written informed consent, according to local guidelines, signed by the subjects and/or by the parents or legal guardian prior to any study related screening procedures are performed
I am willing and able to follow the study's schedule and procedures.
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Exclusion Criteria

Subject has permanently discontinued from study treatment in the parent protocol due to any reason
My medication (dabrafenib/trametinib) is approved and paid for in my country.
I have been part of a study where I received dabrafenib and/or trametinib with another drug.
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Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dabrafenib and/or trametinib as per their previous treatment in the parent study

Duration not specified

Long-term Follow-up

Participants are monitored for long-term effects, including developmental and clinical assessments

Up to approximately 7 years

Treatment Details

Interventions

  • Dabrafenib
  • Trametinib
Trial OverviewThe study is a long-term follow-up focusing on children treated with dabrafenib and/or trametinib for brain tumors. It aims to assess the ongoing effects of these medications over an extended period after initial trials.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Dabrafenib and/or trametinibExperimental Treatment2 Interventions
Patients in this study may receive one of the following treatments received in the parent study which are: * Patients who received monotherapy of either of dabrafenib or trametinib * Patients who received combination of dabrafenib and trametinib * Patients who discontinued treatment on parent study are still offered to participate in long-term follow-up

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?

Novartis Pharmaceuticals

Lead 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

In a case series of 4 patients with BRAF V600E primary brain tumors, dual therapy with dabrafenib and trametinib led to near-complete or complete clinical responses in three patients after 8 weeks, demonstrating significant efficacy.
The combination therapy not only showed greater effectiveness than dabrafenib alone but also helped reduce skin-related side effects, such as keratosis, highlighting its potential to improve patient tolerability during treatment.
Dual BRAF/MEK therapy in BRAF V600E-mutated primary brain tumors: a case series showing dramatic clinical and radiographic responses and a reduction in cutaneous toxicity.Bernstein, A., Mrowczynski, OD., Greene, A., et al.[2023]
Dabrafenib plus trametinib demonstrated significant efficacy in treating BRAFV600E mutation-positive high-grade glioma, with a 33% objective response rate in 45 patients, including complete and partial responses.
In the low-grade glioma cohort, the treatment showed even higher efficacy, with a 69% objective response rate in 13 patients, indicating that this combination therapy could be a promising option for patients with these types of tumors.
Dabrafenib plus trametinib in patients with BRAFV600E-mutant low-grade and high-grade glioma (ROAR): a multicentre, open-label, single-arm, phase 2, basket trial.Wen, PY., Stein, A., van den Bent, M., et al.[2022]
In a phase I/II study involving 139 pediatric patients with relapsed/refractory malignancies, trametinib was found to have a recommended dose of 0.032 mg/kg for children under 6 years and 0.025 mg/kg for those 6 years and older, with manageable safety profiles and no dose-limiting toxicities when combined with dabrafenib.
Among 49 patients with BRAF V600-mutant low-grade gliomas, the combination therapy of dabrafenib and trametinib showed a higher objective response rate of 25% compared to 15% for trametinib alone, indicating improved efficacy with the combination treatment.
Efficacy and Safety of Trametinib Monotherapy or in Combination With Dabrafenib in Pediatric BRAF V600-Mutant Low-Grade Glioma.Bouffet, E., Geoerger, B., Moertel, C., et al.[2023]

References

Dual BRAF/MEK therapy in BRAF V600E-mutated primary brain tumors: a case series showing dramatic clinical and radiographic responses and a reduction in cutaneous toxicity. [2023]
Dabrafenib plus trametinib in patients with BRAFV600E-mutant low-grade and high-grade glioma (ROAR): a multicentre, open-label, single-arm, phase 2, basket trial. [2022]
Efficacy and Safety of Trametinib Monotherapy or in Combination With Dabrafenib in Pediatric BRAF V600-Mutant Low-Grade Glioma. [2023]
Dabrafenib plus trametinib is effective in the treatment of BRAF V600-mutated metastatic melanoma patients: analysis of patients from the dabrafenib plus trametinib Named Patient Program (DESCRIBE II). [2023]
FDA Approval Summary: Dabrafenib in combination with trametinib for BRAF V600E mutation-positive low-grade glioma. [2023]
Dabrafenib plus Trametinib: a Review in Advanced Melanoma with a BRAF (V600) Mutation. [2022]
Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial. [2022]
Cerebral infarction after treatment with dabrafenib plus trametinib for BRAF-V600E-positive non-small cell lung cancer: A case report. [2023]