Dabrafenib + Trametinib for Brain Tumors

(PNOC037 Trial)

Recruiting at 1 trial location

Overseen By Kelly Hitchner

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Francisco

Must be taking: Dabrafenib, Trametinib

Must not be taking: Investigational agents

Disqualifiers: IDH1/2 mutation, Histone H3 mutation, NF-1, 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: 30

Duration: 12-24 months

96 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two drugs, dabrafenib and trametinib, when used less frequently or stopped altogether for certain brain tumors. These kinase inhibitors block abnormal proteins that promote tumor growth. The study targets patients with low-grade gliomas that have a specific gene mutation called BRAF V600. Suitable participants have had a BRAF V600 mutant brain tumor and are currently on these drugs or have used them before. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Do I need to stop my current medications to join the trial?

The trial does not specify that you must stop all current medications, but it does mention that certain medications affected by the induction of specific enzymes should be avoided or used cautiously. It's important to discuss your current medications with the study team to ensure there are no interactions with the trial drugs.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of dabrafenib and trametinib is well-tolerated in patients with BRAF V600 mutations. One study found that this treatment led to better responses and longer periods without disease progression compared to standard chemotherapy. It also demonstrated a better safety profile, with fewer serious side effects.

Another study focused on children and teenagers with similar genetic markers and found the treatment promising, particularly for those with difficult-to-treat brain tumors. Although side effects can occur, these studies suggest that dabrafenib and trametinib are generally well-tolerated by patients with BRAF-altered gliomas. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about dabrafenib and trametinib for brain tumors because these treatments specifically target the BRAF V600 mutation, which is a common driver in low-grade gliomas. Unlike traditional chemotherapy and radiation, which can affect healthy cells too, these drugs are targeted therapies designed to disrupt the cancer cells' growth pathways. Moreover, dabrafenib and trametinib are taken orally, offering a non-invasive option compared to some standard treatments. By honing in on the genetic mutations underlying the tumors, these medications hold promise for more effective and potentially less toxic cancer management.

What evidence suggests that this trial's treatments could be effective for low-grade gliomas with a BRAF V600 mutation?

This trial will evaluate the combination of dabrafenib and trametinib for treating brain tumors, specifically gliomas with the BRAF V600 mutation. Studies have shown that using dabrafenib and trametinib together effectively treats these tumors. Research indicates that patients with this mutation often experience better survival rates and outcomes with these targeted treatments. Early findings suggest that this drug combination can block abnormal proteins that promote tumor growth, helping to prevent the tumor from spreading. Additionally, this combination has shown promising results in children and teenagers whose conditions have returned or are difficult to treat. The treatment typically has manageable side effects, making it a suitable option for patients with this specific genetic change. Participants in this trial will be assigned to different arms, including those where treatment stops after a certain period and those where treatment is gradually reduced. ^{5 6 7 8 9}

Who Is on the Research Team?

Sabine Mueller, MD, PHD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for patients with low-grade gliomas, a type of brain tumor, that have a specific genetic change called BRAF V600 mutation. Details on who can join or reasons for exclusion are not provided.

Inclusion Criteria

I am between 1 and 24 years old.

My low-grade glioma is WHO Grade I or II with a confirmed BRAF V600 mutation.

My tumor can be measured and is larger than twice the thickness of a CT scan slice.

Exclusion Criteria

My tumor has specific known genetic changes.

My HIV is stable and not severely weakening my immune system.

Participants who are receiving any other investigational agents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dabrafenib and trametinib for a minimum of 12 cycles and up to a maximum of 24 cycles

12-24 months

Monthly visits for each cycle

Weaning or Stopping

Participants either stop treatment or continue with a weaning regimen for 6 additional cycles

6 months

Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Follow-up at 30 days, then periodically up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Dabrafenib
• Trametinib

Trial Overview The study tests the effectiveness of reducing doses of dabrafenib and trametinib, medications that block proteins causing tumor growth in patients with certain brain tumors. It aims to find the best dosing strategy after initial treatment lasting 12-24 months.

How Is the Trial Designed?

Group I: Cohort 2: Arm B (Recurrent LGG, Dabrafenib, Trametinib followed by weaning) Experimental Treatment 5 Interventions

Participants with recurrent/progressive BRAF V600 mutant LGGs receive dabrafenib PO twice per day (BID) and trametinib PO once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days for a minimum of 12 cycles and continues until confirmed best response or for up to a maximum of 24 cycles in the absence of disease progression or unacceptable toxicity. Participants then receive dabrafenib PO BID and trametinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Participants also undergo ECHO, MRI, and blood sample collection throughout the study and may optionally undergo lumbar puncture for collection of CSF.

Group II: Cohort 2: Arm A (Recurrent LGG, Dabrafenib, Trametinib followed by treatment stop) Experimental Treatment 5 Interventions

Participants with recurrent/progressive BRAF V600 mutant LGGs receive dabrafenib PO twice per day (BID) and trametinib PO once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days for a minimum of 12 cycles and continues until confirmed best response or for up to a maximum of 24 cycles in the absence of disease progression or unacceptable toxicity. Participants then stop treatment with dabrafenib and trametinib. Participants also undergo ECHO, MRI, and blood sample collection throughout the study and may optionally undergo lumbar puncture for collection of CSF.

Group III: Cohort 1: Arm B (Newly diagnosed, Dabrafenib, Trametinib followed by weaning) Experimental Treatment 5 Interventions

Participants with newly diagnosed BRAF V600 mutant LGGs receive dabrafenib PO twice per day (BID) and trametinib PO once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days for a minimum of 12 cycles and continues until confirmed best response or for up to a maximum of 24 cycles in the absence of disease progression or unacceptable toxicity. Participants then receive dabrafenib PO BID and trametinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Participants also undergo ECHO, MRI, and blood sample collection throughout the study and may optionally undergo lumbar puncture for collection of CSF.

Group IV: Cohort 1: Arm A (Newly diagnosed, Dabrafenib, Trametinib followed by treatment stop) Experimental Treatment 5 Interventions

Participants with newly diagnosed BRAF V600 mutant LGGs receive dabrafenib PO twice per day (BID) and trametinib PO once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days for a minimum of 12 cycles and continues until confirmed best response or for up to a maximum of 24 cycles in the absence of disease progression or unacceptable toxicity. Participants then stop treatment with dabrafenib and trametinib. Participants also undergo ECHO, MRI, and blood sample collection throughout the study and may optionally undergo lumbar puncture for collection of CSF.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Rising Tide Foundation

Collaborator

Trials

17

Recruited

6,200+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11606206/

Dabrafenib plus trametinib in low-grade versus high-grade ... Dabrafenib plus trametinib is associated with favorable outcomes in gliomas, especially among those with lower age, BRAF V600 mutation, longer dual blockage ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07110246

NCT07110246 | Dabrafenib and Trametinib for BRAF V600 ... This phase II trial studies how well de-escalating the drugs dabrafenib and trametinib works in treating patients with low-grade gliomas ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.00558

Phase II Trial of Dabrafenib Plus Trametinib in Relapsed/ ... Dabrafenib plus trametinib is a promising targeted therapy option for children and adolescents with relapsed/refractory BRAF V600–mutant HGG.

4. journals.lww.com journals.lww.com/md-journal/fulltext/2024/12060/emerging_paradigm__molecularly_targeted_therapy.27.aspx

Emerging paradigm: Molecularly targeted therapy with ... Dabrafenib and Trametinib offer a promising targeted therapy for juvenile gliomas with BRAF V600 mutations, with better survival outcomes and manageable safety ...

5. cda-amc.ca cda-amc.ca/sites/default/files/DRR/2025/PX0375_Dabrafenib_Trametinib_CL_report_draft.pdf

Review Report The objective of the Clinical Review is to review and critically appraise the evidence on the beneficial and harmful effects of dabrafenib plus trametinib in ...

6. 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 ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/PMC7715318

LGG-49. SAFETY AND EFFICACY OF TRAMETINIB (T) ... We report interim analysis results of pediatric patients with recurrent/refractory BRAF V600-mutant LGG treated with either T (MEK1/2 inhibitor) monotherapy or ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02684058

NCT02684058 | Study of Efficacy and Safety of Dabrafenib ... The purpose of this study was to investigate the activity of dabrafenib in combination with trametinib in children and adolescent patients with BRAF V600 ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2772610X25000248

Dabrafenib and trametinib either in combination or as ... We report patient data from a MAP for pediatric patients with BRAF-altered gliomas or other rare tumors, seeking clinical benefit from dabrafenib and/or ...