Dabrafenib + Trametinib for Brain Tumors

Not currently recruiting at 83 trial locations

Overseen By Novartis Pharmaceuticals

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: Novartis Pharmaceuticals

Must be taking: Dabrafenib, Trametinib

Disqualifiers: Severe toxicities, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Duration not specified

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on understanding the long-term effects of two cancer treatments, dabrafenib (a BRAF inhibitor) and trametinib (a MEK inhibitor), in children with brain tumors. Participants will either continue the treatment received in a previous study or start treatment if they previously received chemotherapy. The trial aims to determine how these treatments work over time and identify who might benefit the most. Suitable candidates include children already receiving dabrafenib or trametinib who have demonstrated adherence to a treatment plan. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, aiming to understand how it benefits more patients.

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 is the safety track record for dabrafenib and trametinib?

Research shows that dabrafenib and trametinib are usually well-tolerated by patients. Studies have found that using these two drugs together leads to better responses and longer periods without disease progression compared to standard chemotherapy for certain brain tumors. This often results in patients living longer without their condition worsening.

The FDA has approved dabrafenib and trametinib for treating certain cancers, indicating their safety. However, like many treatments, they can have side effects. Common side effects of this combination include fever, rash, and chills, which are generally manageable with proper care.

In young patients, this combination has demonstrated a better safety profile than traditional chemotherapy, usually causing fewer or less severe side effects compared to older treatments.

Overall, while possible side effects exist, research indicates that dabrafenib and trametinib are generally safe when used under medical supervision. Always discuss potential risks and benefits with a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about dabrafenib and trametinib for brain tumors because they specifically target genetic mutations that drive tumor growth. Unlike standard treatments like surgery, radiation, or chemotherapy, which can affect both healthy and cancerous cells, these drugs inhibit the BRAF and MEK pathways that are often mutated in certain brain tumors. This targeted approach not only aims to halt tumor progression more effectively but also has the potential to reduce side effects by sparing healthy tissues.

What is the effectiveness track record for dabrafenib and trametinib in treating brain tumors?

Research has shown that the drugs dabrafenib and trametinib can effectively treat certain brain tumors. In this trial, participants may receive dabrafenib alone, trametinib alone, or a combination of both. Studies have found that using these two drugs together leads to significant tumor shrinkage in 58% of patients with brain tumors that have spread to the brain. The TADPOLE trial reported a 47% overall response rate, with some patients experiencing nearly two years without disease progression. This combination proved more effective at shrinking tumors than standard chemotherapy. Dabrafenib alone has also produced positive results for patients with brain tumors. These findings support the use of these treatments for brain tumors, offering hope for better management of the condition. ^{6 7 8 9 10}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Dabrafenib
• Trametinib

Trial Overview The 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.

How Is the Trial Designed?

Group I: Dabrafenib and/or trametinib Experimental Treatment 2 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

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

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

Dabrafenib, a selective BRAF kinase inhibitor, was found to be safe and well-tolerated in a phase 1 trial involving 184 patients with incurable solid tumors, with a recommended phase 2 dose established at 150 mg twice daily.

The treatment showed significant efficacy, particularly in patients with Val600 BRAF-mutant melanoma, where 69% of patients experienced a response, and notable reductions in brain metastases were observed in 90% of patients with untreated brain lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial. Falchook, GS., Long, GV., Kurzrock, R., et al.[2022]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

A 61-year-old man with BRAF V600E-mutated lung adenocarcinoma experienced cerebral infarction after treatment with dabrafenib and trametinib, highlighting a potential risk associated with this therapy.

Despite being considered safe in previous trials, this case suggests that clinicians should monitor for signs of cerebral infarction during treatment, especially in patients with complications like disseminated intravascular coagulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebral infarction after treatment with dabrafenib plus trametinib for BRAF-V600E-positive non-small cell lung cancer: A case report. Taniguchi, Y., Tamiya, A., Yanagisawa, A., et al.[2023]

The FDA approved the combination of dabrafenib and trametinib for treating pediatric patients with low-grade glioma (LGG) with a BRAFV600E mutation, marking the first systemic therapy approved for this condition.

In a clinical trial with 110 patients, the combination therapy showed a significantly higher overall response rate of 47% compared to 11% for the standard treatment of carboplatin and vincristine, along with longer progression-free survival of 20.1 months versus 7.4 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Dabrafenib in combination with trametinib for BRAF V600E mutation-positive low-grade glioma. Barbato, MI., Nashed, J., Bradford, D., et al.[2023]

In a compassionate-use setting involving 271 patients with BRAF V600-mutant unresectable or metastatic melanoma, the combination of dabrafenib and trametinib demonstrated a high overall response rate of 67.3% and a median overall survival of 20.0 months for BRAFi-naive patients.

The treatment was well tolerated with no new safety concerns, showing significant clinical activity even in patients with brain metastases, indicating its effectiveness across different treatment lines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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). Atkinson, V., Sandhu, S., Hospers, G., et al.[2023]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

The combination of dabrafenib and trametinib significantly improves progression-free survival and overall survival in patients with unresectable or metastatic melanoma with a BRAF (V600E/K) mutation, compared to monotherapy with dabrafenib or vemurafenib, based on results from two large phase III studies.

This combination therapy is well-tolerated, showing no increase in overall toxicity compared to monotherapy, and results in fewer skin-related adverse events, likely due to reduced activation of the MAPK pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dabrafenib plus Trametinib: a Review in Advanced Melanoma with a BRAF (V600) Mutation. Dhillon, S.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11341626/

The effects of dabrafenib and/or trametinib treatment in Braf ... Based on current literature outcomes, dabrafenib and/or trametinib may lead to the median PFS of 6.10 months and median OS as 22.73 months for ...

2. onclive.com onclive.com/view/longterm-and-brain-mets-data-demonstrate-strong-dabrafenibtrametinib-efficacy-in-melanoma

Long-Term and Brain Mets Data Demonstrate Strong ... An analysis of the phase II COMBI-MB trial results showed that dabrafenib plus trametinib achieved an intracranial response (IR) rate of 58% in ...

3. nature.com nature.com/articles/nrclinonc.2012.109

BRAF kinase inhibitor shows efficacy in brain metastases In a phase III clinical trial presented at the annual ASCO conference, the selective BRAF inhibitor dabrafenib was shown to improve ...

4. lilabeanfoundation.com lilabeanfoundation.com/better-treatment-option-for-some-low-grade-glioma-patients-becomes-a-reality

Better Treatment Option for some Low-Grade Glioma ... This came after the TADPOLE trial showed an overall response rate of 47% and median progression-free survival of 20.1 months for the Tafinlar + Mekinist ...

5. cancer.gov cancer.gov/news-events/cancer-currents-blog/2022/glioma-brain-cancer-dabrafenib-trametinib

Dabrafenib–Trametinib Combo Better than Chemo for ... The combination of dabrafenib (Tafinlar) and trametinib (Mekinist) was safer and better than standard chemotherapy at shrinking tumors and keeping them at bay.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12133646/

The safety and efficacy of dabrafenib plus trametinib for ... In a phase 2 study, dabrafenib was beneficial in 39.2% of patients with metastatic brain melanoma who had never received medication before, as ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/202806s022lbl.pdf

TAFINLAR (dabrafenib) - accessdata.fda.gov TAFINLAR is not for use in treating people with colorectal cancer or wild-type BRAF solid tumors. Your healthcare provider will perform a test to make sure ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4109288/

RAF Inhibitor Dabrafenib (GSK2118436) is Active in ... A Phase I trial of dabrafenib was conducted to evaluate safety and tolerability in patients with incurable solid tumours. Efficacy at the ...

9. novartis.com novartis.com/us-en/sites/novartis_us/files/tafinlar.pdf

tafinlar.pdf TAFINLAR is not for use in treating people with colorectal cancer or wild-type BRAF solid tumors. Your healthcare provider will perform a test to make sure ...

10. nejm.org nejm.org/doi/full/10.1056/NEJMoa2303815

Dabrafenib plus Trametinib in Pediatric Glioma with BRAF ... Dabrafenib plus trametinib resulted in significantly more responses, longer progression-free survival, and a better safety profile than standard chemotherapy ...