Low Grade GliomaPhase 1/2NCT06712875
MAPK Inhibition Combined With Anti-PD1 Therapy for BRAF-altered Pediatric Gliomas
A Phase 1/2 study testing Trametinib and Nivolumab and Dabrafenib, trametinib, nivolumab in people with Low Grade Glioma and High Grade Glioma, run by Ann & Robert H Lurie Children's Hospital of Chicago at 3 sites in United States.
Trial summary
Pediatric gliomas harboring BRAF-alterations, commonly BRAFV600 mutation or KIAA1549-BRAF fusion, are currently treated with either chemotherapy or mitogen activated protein kinase (MAPK) inhibitors, such as, dabrafenib and/or trametinib. Read more about this study
- Who is it for?
- Ages 1 year to 26 years
- Conditions the study is for
- Low Grade Glioma, High Grade Glioma
- What is being tested?
- Trametinib and Nivolumab and Dabrafenib, trametinib, nivolumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 3 sitesUnited States
- Study dates
- 1 Apr 2025to Jun 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 26 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Cohort A Only:
- Patients with histologically confirmed diagnosis of pediatric high- or low-grade glioma harboring a KIAA1549-BRAF fusion: Low-grade glioma that is recurrent or progressive OR High-grade glioma that is newly diagnosed or recurrent OR
- Patients with NF1-associated gliomas or NF1-altered glioma: Low-grade glioma that is recurrent or progressive OR High-grade glioma that is newly diagnosed or recurrent OR Transforming glioma that is newly diagnosed or recurrent
- Cohort B Only:
- Patients with histologically confirmed diagnosis of pediatric low-grade glioma harboring a BRAFV600 mutation that is recurrent or progressive OR
- Patients with histologically confirmed diagnosis of non-brainstem pediatric high-grade glioma harboring BRAFV600 mutation that is newly diagnosed, recurrent, or progressive
Show all 22Show fewer
- All Cohorts:
- Patients must be ≥1 and ≤26 years of age at the time of enrollment.
- Patients must have a performance status of Karnofsky >50% for patients >16 years old and Lansky >50% for patients <16 years old.
- Patients must have adequate organ and bone marrow function
- The effects of dabrafenib, trametinib, and nivolumab on the developing human fetus are unknown. For this reason, patients of childbearing potential (POCBP) and patients with sperm-producing reproductive capacity (PWSPRC) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from time of informed consent for the duration of study participation and for 30 days following completion of therapy. POCBP must have a negative pregnancy test.
- Patients with neurological deficits that are stable for a minimum of 1 week prior to enrollment are eligible.
- Note: A baseline detailed neurological exam should clearly document the neurological status of the patient at the time of enrollment on the study.
- Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to enrollment. Total dexamethasone dose at time of enrollment must be less than or equal to 2 mg/day total or 0.5 mg/kg/day, whichever is smaller.
- LGG Only
- Patients must have received a prior BRAF inhibitor (first or second generation), MEK inhibitor, or a combination. The response to this therapy must be known and information provided at study enrollment.
- Patients must have recovered from acute treatment-related toxicities (defined as <Grade 1, excludes alopecia) prior to entering this study.
- HGG Only
- Patients must have received prior radiotherapy >12 weeks prior to enrollment.
- Patients must have recovered from acute treatment-related toxicities (defined as <Grade 1, excludes alopecia) prior to entering this study.
- NF1 patients with transforming gliomas and high-grade gliomas are eligible regardless of prior systemic therapy.
- Patients who have received prior radiation therapy must have experienced progression post-radiation OR have measurable disease defined as residual tumor >1cm in at least one dimension
Who cannot join
- Patients with disseminated disease.
- Patients who have had prior radiation therapy <12 weeks prior to registration.
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1) (with the exception of alopecia).
- Patients who receiving any other investigational agents. Note: There will be a 21-day washout period for all chemotherapeutic agents, a washout period of two half-lives for any targeted agents (e.g., MAPK inhibitors), and/or a washout period of 4 weeks for any antibody therapies (e.g., bevacizumab).
- Patients who have a history of allergic reactions attributed to compounds of similar chemical or biological composition to dabrafenib, trametinib, or nivolumab.
- Patients who have received MAPK inhibitor and checkpoint blockade combination therapy.
Show all 28Show fewer
- Note: Patients may have received MAPK inhibitor monotherapy or checkpoint blockade monotherapy.
- Patients who previously discontinued BRAF inhibitor (type 1 inhibitor or dimer inhibitor, such as, DAY101), MEK inhibitor, or the combination because of grade 3 or higher toxicity or clinically significant grade 2 toxicity requiring discontinuation of therapy are not eligible.
- Patients with the following:
- Known autoimmune disorders
- Immune disorders
- Immunodeficiencies
- Patients with Crohn's disease, ulcerative colitis, or other inflammatory bowel disease.
- Patients with active pancreatitis or history of pancreatitis within the last 3 months.
- Patients with active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis requiring treatment with systemic steroids.
- Patients who have a known active Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C infection are ineligible. Patient must have documented evidence of negative tests for the presence of HIV, Hepatitis B surface antigen, and Hepatitis C (anti-HCV antibody OR Hep C RNA-qualitative).
- Patients who have received a major surgical procedure ≤ 28 days of beginning study treatment, or minor surgical procedures (including VP shunt placement or stereotactic biopsy of the tumor) ≤ 7 days are not eligible.
- Patients who are taking herbal preparations. These medications include but are not limited to St. John's wort, kava, ephedra (ma hung), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng. Cannabis products of any type are not allowed throughout the study. Patients should stop using these herbal medications or cannabis products 7 days prior to enrollment.
- Patients who are pregnant. Patients of childbearing potential must have a negative serum or urine pregnancy test. (If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.)
- Patients who are lactating (unless they have agreed to not breastfeed). Breastfeeding patients are excluded from this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies.
- Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic, or other organ dysfunction), that in the opinion of the investigator would compromise the patient's ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results.
- Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen for this trial.
- Patients with bulky tumor on imaging are ineligible. Bulky tumor is defined as:
- Tumor with any evidence of clinically significant uncal herniation or midline shift
- Tumor with diameter of >5cm in one dimension on T2/FLAIR except for those patients with newly diagnosed HGG treated following irradiation without signs of tumor progression. For the latter group, a maximum diameter of contrast enhancing solid or necrotic tumor and of T2/FLAIR abnormality will be 5 cm and 8 cm, respectively.
- Tumor that in the opinion of the site investigator, shows significant mass effect
- Metastatic disease: Patients with ≤ 5 separate foci of metastatic disease not causing mass effect on adjacent parenchyma and each measuring less than 0.5 cm in maximum diameter will be eligible for this arm of the study. Patients with leptomeningeal disease are eligible.
- Multi-focal disease (patients with multi-focal parenchymal disease will be eligible if the sum of the product of the maximum perpendicular diameters of all measurable non-contiguous lesions is less than 16 cm2 based on the T2/FLAIR abnormality).
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Monica Newmark, 3122274847, mnewmark@luriechildrens.org
Ashley Plant-Fox, MD, 312-227-4874, aplant@luriechildrens.org
- Not yet recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Sameer Farouk, faroukss@mskcc.org
- Not yet recruiting
Children's National Hospital
Washington D.C., District of Columbia, 20010
Hameenat Adekoya, 202-476-3898, HAdekoya@childrensnational.org
About this study
Official title: A Pilot Study Evaluating the Toxicity and Clinical Benefit of Mitogen-activated Protein Kinase (MAPK) Pathway Inhibition Combined With Programmed Cell Death-1 Checkpoint Blockade (Anti-PD1) for the Treatment of BRAF-altered Pediatric Gliomas
Pediatric gliomas harboring BRAF-alterations, commonly BRAFV600 mutation or KIAA1549-BRAF fusion, are currently treated with either chemotherapy or mitogen activated protein kinase (MAPK) inhibitors, such as, dabrafenib and/or trametinib. Unfortunately, some BRAF-altered gliomas can progress or have rebound growth after discontinuation of therapy. Data from BRAFV600E-mutant melanoma has shown potential synergy between MAPK inhibition and anti-programmed cell death 1 (anti-PD1) checkpoint blockade. Anti-PD1 therapy, such as, nivolumab can block the PD1 receptor on T cells, a marker of T cell exhaustion, allowing a continued or more robust anti-tumor immune response. Here, investigators will combine MAPK inhibition with anti-PD1 therapy in recurrent, refractory low grade BRAF-altered glioma and newly diagnosed or recurrent BRAF-altered or NF-altered high grade glioma.
Read the detailed description
This is a pilot study evaluating the toxicity and early efficacy of dabrafenib and/or trametinib combined with nivolumab for the treatment of BRAF-altered or NF altered gliomas. While dabrafenib, trametinib, and nivolumab have been used for pediatric gliomas in previous studies, this will be the first pediatric study evaluating the combination of these agents.
This study will evaluate the use of dabrafenib, trametinib, and nivolumab in patients in recurrent, refractory, or progressive low grade gliomas harboring BRAFV600 mutations who have previously been treated with MAPK inhibition alone. The same combination will be explored in newly diagnosed or recurrent BRAFV600 mutant high grade glioma.
This study will also evaluate the use of trametinib and nivolumab in patients with recurrent, refractory, or progressive low grade gliomas harboring a KIAA1549 BRAF fusion who have previously been treated with MAPK inhibition alone. The same combination will be explored in NF altered transforming or high grade glioma or high grade glioma harboring a KIAA1549 BRAF fusion.
The objective of this study is to understand the safety and tolerability of the combination of dabrafenib, trametinib, and/or nivolumab in pediatrics. Secondarily, this study will evaluate for an early efficacy signal of the combination therapy and compare to historical treatment response to MAPK inhibition alone.
- Conditions
- Low Grade Glioma, High Grade Glioma
- Being tested
- Trametinib and Nivolumab, Dabrafenib, trametinib, nivolumab
- Keywords
- BRAF, BRAFV600, KIAA1549 BRAF fusion, nivolumab, dabrafenib, trametinib, MAPK inhibition combined with anti-PD1 immunotherapy, recurrent low grade glioma, high grade glioma
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trametinib and NivolumabDrug
Trametinib combined with nivolumab (Cohort A)
Dabrafenib, trametinib, nivolumabDrug
Dabrafenib + trametinib combined with nivolumab (Cohort B)
| Study group | Role | What they receive |
|---|---|---|
| Trametinib combined with nivolumab (Cohort A) | Experimental | Patients with histologically confirmed diagnosis of pediatric high- or low-grade glioma harboring a KIAA1549-BRAF fusion. Patients with NF1-associated gliomas or NF1-altered glioma.
Patients in Cohort A will receive trametinib and nivolumab combination therapy. Trametinib will be administered at 0.025 mg/kg/dose orally once daily.
Nivolumab will be administered at 6 mg/kg/dose intravenously every 4 weeks.
Cycle length will be every 28 days. Treatment will include 1 year or 13 cycles of combination therapy, whichever comes first. For patients with high grade glioma, therapy can be continued beyond the 13 cycles if they are deemed to have clinical benefit from the therapy. Patients will be followed for up to 5 years to evaluate clinical endpoints. Receives: Drug: Trametinib and Nivolumab |
| Dabrafenib + trametinib combined with nivolumab (Cohort B) | Experimental | Patients with histologically confirmed diagnosis of pediatric low-grade glioma harboring a BRAFV600 mutation that is recurrent or progressive or non-brainstem pediatric high-grade glioma harbor ng BRAFV600 mutation that is newly diagnosed, recurrent, or progressive.
Cohort B will receive trametinib, nivolumab dabrafenib combination therapy. Trametinib will be administered at 0.025 mg/kg/dose orally once daily.
Nivolumab will be administered at 6 mg/kg/dose intravenously every 4 weeks. Dabrafenib will be administered at a dose of 5.25 mg/kg/day orally divided into two doses, which shall be taken 12 hours apart.
Cycle length will be every 28 days. Treatment will include 1 year or 13 cycles of combination therapy, whichever comes first. For patients with high grade glioma, therapy can be continued beyond the 13 cycles if they are deemed to have clinical benefit from the therapy. Patients will be followed for up to 5 years to evaluate clinical endpoints. Receives: Drug: Dabrafenib, trametinib, nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety based on number of participants with treatment-related adverse events based on scoring from CTCAE v4.0
This study will utilize a rolling 6 design and enroll 12 evaluable patients in each cohort (Cohort A and B). Two dose levels will be utilized to assess safety and tolerability. Dose level 1 includes 100% dosing of dabrafenib and/or trametinib and nivolumab. A dose level -1 will be utilized if dose level 1 is not tolerable and will include 100% dosing of nivolumab with 70% dosing of dabrafenib and/or trametinib.
Measured: The dose limiting toxicity (DLT) period is 28 days.
Secondary outcomes (4)
Response assessment
Objective response rate will be utilized to assess response to combination therapy. Magnetic resonance imaging (MRI) will be evaluated for response utilizing RANO/iRANO criteria. Best response and duration of response be assessed. An objective response is a partial or complete response (PR or CR) sustained for at least 12 weeks.
Measured: From enrollment through end of treatment at 1 year
Assessment of "Better Response"
At enrollment, information will be entered by the study team regarding prior treatment with MAPK inhibition alone. The best response and duration of this response will be recorded. This will be compared to response on study treatment. A "better response" would be considered an improvement of best response from stable disease to partial response, partial response to complete response, or progressive disease to stable disease OR a similar best response that is maintained for 12 weeks longer or more.
Measured: From enrollment to the end of treatment at 1 year
Progression free survival
Progression will be determined by magnetic resonance imaging (MRI) assessment using RANO/iRANO criteria.
Measured: From enrollment through long term follow up (5 years post treatment)
Overall Survival (OS)
Overall survival will be assessed by time to event (death).
Measured: Time of enrollment through long term follow up (5 years post treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2024
- Study start1 Apr 2025
- Primary completionDec 2028 (estimated)
- Study completionJun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Low Grade GliomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Pilot study evaluating toxicity and early efficacy
- Masking
- None (open label)
- Enrolment
- 27 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ann & Robert H Lurie Children's Hospital of Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ashley S. Plant, MD, Ann & Robert H Lurie Children's Hospital of Chicago
- Investigators
- Ashley Plant-Fox, MD, Principal investigator, Ann & Robert H Lurie Children's Hospital of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06712875
- Sponsor's protocol ID
- LCH24C02
- Status last verified
- Jul 2026
- First submitted
- 26 Nov 2024
- Last updated
- 10 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: I do not plan to provide individual participant data except in de-identified format in publication or amongst study investigators
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study Evaluating the Toxicity and Clinical Benefit of Mitogen-activated Protein Kinase (MAPK) Pathway Inhibition Combined With Programmed Cell Death-1 Checkpoint Blockade (Anti-PD1) for the Treatment of BRAF-altered Pediatric Gliomas
- ClinicalTrials.gov ID
- NCT06712875
- Acronym / sponsor ID
- LCH24C02
- Conditions
- Low Grade Glioma, High Grade Glioma
- Keywords
- BRAF, BRAFV600, KIAA1549 BRAF fusion, nivolumab, dabrafenib, trametinib, MAPK inhibition combined with anti-PD1 immunotherapy, recurrent low grade glioma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 27 participants (estimated)
- Lead sponsor
- Ann & Robert H Lurie Children's Hospital of ChicagoUniversity, hospital or other
- Study start
- 1 Apr 2025 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Jun 2029 (estimated)
- First posted
- 2 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pediatric gliomas harboring BRAF-alterations, commonly BRAFV600 mutation or KIAA1549-BRAF fusion, are currently treated with either chemotherapy or mitogen activated protein kinase (MAPK) inhibitors, such as, dabrafenib and/or trametinib. Unfortunately, some BRAF-altered gliomas can progress or have rebound growth after discontinuation of therapy. Data from BRAFV600E-mutant melanoma has shown potential synergy between MAPK inhibition and anti-programmed cell death 1 (anti-PD1) checkpoint blockade. Anti-PD1 therapy, such as, nivolumab can block the PD1 receptor on T cells, a marker of T cell exhaustion, allowing a continued or more robust anti-tumor immune response. Here, investigators will combine MAPK inhibition with anti-PD1 therapy in recurrent, refractory low grade BRAF-altered glioma and newly diagnosed or recurrent BRAF-altered or NF-altered high grade glioma.
Detailed description
This is a pilot study evaluating the toxicity and early efficacy of dabrafenib and/or trametinib combined with nivolumab for the treatment of BRAF-altered or NF altered gliomas. While dabrafenib, trametinib, and nivolumab have been used for pediatric gliomas in previous studies, this will be the first pediatric study evaluating the combination of these agents.
This study will evaluate the use of dabrafenib, trametinib, and nivolumab in patients in recurrent, refractory, or progressive low grade gliomas harboring BRAFV600 mutations who have previously been treated with MAPK inhibition alone. The same combination will be explored in newly diagnosed or recurrent BRAFV600 mutant high grade glioma.
This study will also evaluate the use of trametinib and nivolumab in patients with recurrent, refractory, or progressive low grade gliomas harboring a KIAA1549 BRAF fusion who have previously been treated with MAPK inhibition alone. The same combination will be explored in NF altered transforming or high grade glioma or high grade glioma harboring a KIAA1549 BRAF fusion.
The objective of this study is to understand the safety and tolerability of the combination of dabrafenib, trametinib, and/or nivolumab in pediatrics. Secondarily, this study will evaluate for an early efficacy signal of the combination therapy and compare to historical treatment response to MAPK inhibition alone.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Pilot study evaluating toxicity and early efficacy
| Arm | Type | Receives |
|---|---|---|
| Trametinib combined with nivolumab (Cohort A) | Experimental | Drug: Trametinib and NivolumabPatients with histologically confirmed diagnosis of pediatric high- or low-grade glioma harboring a KIAA1549-BRAF fusion. Patients with NF1-associated gliomas or NF1-altered glioma. Patients in Cohort A will receive trametinib and nivolumab combination therapy. Trametinib will be administered at 0.025 mg/kg/dose orally once daily. Nivolumab will be administered at 6 mg/kg/dose intravenously every 4 weeks. Cycle length will be every 28 days. Treatment will include 1 year or 13 cycles of combination therapy, whichever comes first. For patients with high grade glioma, therapy can be continued beyond the 13 cycles if they are deemed to have clinical benefit from the therapy. Patients will be followed for up to 5 years to evaluate clinical endpoints. |
| Dabrafenib + trametinib combined with nivolumab (Cohort B) | Experimental | Drug: Dabrafenib, trametinib, nivolumabPatients with histologically confirmed diagnosis of pediatric low-grade glioma harboring a BRAFV600 mutation that is recurrent or progressive or non-brainstem pediatric high-grade glioma harbor ng BRAFV600 mutation that is newly diagnosed, recurrent, or progressive. Cohort B will receive trametinib, nivolumab dabrafenib combination therapy. Trametinib will be administered at 0.025 mg/kg/dose orally once daily. Nivolumab will be administered at 6 mg/kg/dose intravenously every 4 weeks. Dabrafenib will be administered at a dose of 5.25 mg/kg/day orally divided into two doses, which shall be taken 12 hours apart. Cycle length will be every 28 days. Treatment will include 1 year or 13 cycles of combination therapy, whichever comes first. For patients with high grade glioma, therapy can be continued beyond the 13 cycles if they are deemed to have clinical benefit from the therapy. Patients will be followed for up to 5 years to evaluate clinical endpoints. |
Who may qualify
- Ages
- 1 year to 26 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (22 listed)
- Patients with histologically confirmed diagnosis of pediatric high- or low-grade glioma harboring a KIAA1549-BRAF fusion: Low-grade glioma that is recurrent or progressive OR High-grade glioma that is newly diagnosed or recurrent OR
- Patients with NF1-associated gliomas or NF1-altered glioma: Low-grade glioma that is recurrent or progressive OR High-grade glioma that is newly diagnosed or recurrent OR Transforming glioma that is newly diagnosed or recurrent
- Patients with histologically confirmed diagnosis of pediatric low-grade glioma harboring a BRAFV600 mutation that is recurrent or progressive OR
- Patients with histologically confirmed diagnosis of non-brainstem pediatric high-grade glioma harboring BRAFV600 mutation that is newly diagnosed, recurrent, or progressive
- Patients must be ≥1 and ≤26 years of age at the time of enrollment.
Key exclusion criteria (28 listed)
- Patients with disseminated disease.
- Patients who have had prior radiation therapy <12 weeks prior to registration.
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1) (with the exception of alopecia).
- Patients who receiving any other investigational agents. Note: There will be a 21-day washout period for all chemotherapeutic agents, a washout period of two half-lives for any targeted agents (e.g., MAPK inhibitors), and/or a washout period of 4 weeks for any antibody therapies (e.g., bevacizumab).
- Patients who have a history of allergic reactions attributed to compounds of similar chemical or biological composition to dabrafenib, trametinib, or nivolumab.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Trametinib and NivolumabTrametinib combined with nivolumab (Cohort A) | Drug | Trametinib combined with nivolumab (Cohort A) |
| Dabrafenib, trametinib, nivolumabDabrafenib + trametinib combined with nivolumab (Cohort B) | Drug | Dabrafenib + trametinib combined with nivolumab (Cohort B) |
Primary outcome
Safety based on number of participants with treatment-related adverse events based on scoring from CTCAE v4.0
Time frame: The dose limiting toxicity (DLT) period is 28 days.
This study will utilize a rolling 6 design and enroll 12 evaluable patients in each cohort (Cohort A and B). Two dose levels will be utilized to assess safety and tolerability. Dose level 1 includes 100% dosing of dabrafenib and/or trametinib and nivolumab. A dose level -1 will be utilized if dose level 1 is not tolerable and will include 100% dosing of nivolumab with 70% dosing of dabrafenib and/or trametinib.
4 secondary outcomes
Response assessment
Time frame: From enrollment through end of treatment at 1 year
Assessment of "Better Response"
Time frame: From enrollment to the end of treatment at 1 year
Progression free survival
Time frame: From enrollment through long term follow up (5 years post treatment)
Overall Survival (OS)
Time frame: Time of enrollment through long term follow up (5 years post treatment)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2026.
- Individual participant dataSharing planned: No. I do not plan to provide individual participant data except in de-identified format in publication or amongst study investigators
Related trials for Low Grade Glioma
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
RecruitingPhase 3
A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma
Low Grade Astrocytoma, Low Grade Glioma
RecruitingPhase 2
Dabrafenib and Trametinib for BRAF V600 Mutant Low-Grade Gliomas
BRAF V600 Mutation, Low-grade Glioma
Active, not recruitingPhase 2
Nivolumab in Patients With IDH-Mutant Gliomas With and Without Hypermutator Phenotype
Glioma, Glioblastoma
Active, not recruitingPhase 3
DAY101 vs. Standard of Care Chemotherapy in Pediatric Participants With Low-Grade Glioma Requiring First-Line Systemic Therapy (LOGGIC/FIREFLY-2)
Low-grade Glioma, Rapidly Accelerated Fibrosarcoma (RAF) Altered Glioma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ashley Plant-Fox, MD principal investigator
Ann & Robert H Lurie Children's Hospital of Chicago
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Trametinib and Nivolumab and Dabrafenib, trametinib, nivolumab in people with Low Grade Glioma and High Grade Glioma, run by Ann & Robert H Lurie Children's Hospital of Chicago at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Monica Newmark (312-227-4847, mnewmark@luriechildrens.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety based on number of participants with treatment-related adverse events based on scoring from CTCAE v4.0 (time frame: The dose limiting toxicity (DLT) period is 28 days.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2026.