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New treatment option for Low Grade Glioma
Official title MAPK Inhibition Combined With Anti-PD1 Therapy for BRAF-altered Pediatric Gliomas
ClinicalTrials.gov ID: NCT06712875
What this study is testing
What is Trametinib and Nivolumab?
Trametinib and Nivolumab is an investigational medicine, being studied as a potential treatment for low grade glioma.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 1 to 26
You may be able to join if
- 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...
- Patients with NF1-associated gliomas or NF1-altered glioma: Low-grade glioma that is recurrent or progressive OR High-grade glioma that is newly...
- 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...
You likely can't join if
- 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...
- Patients who receiving any other investigational agents. Note: There will be a 21-day washout period for all chemotherapeutic agents, a washout...
- Patients who have a history of allergic reactions attributed to compounds of similar chemical or biological composition to dabrafenib, trametinib, or...
- Patients who have received MAPK inhibitor and checkpoint blockade combination therapy. Note: Patients may have received MAPK inhibitor monotherapy or...
See the full eligibility criteria
Who can 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...
- 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...
- 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 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...
- 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...
- 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
What rules you out
- 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)...
- 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. 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...
- 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...
- 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...
- 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...
- 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...
- Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or how well it works 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...
- 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...
- 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 study team makes the final eligibility decision.
Where it's taking place
- Washington D.C., District of Columbia, United States
- Chicago, Illinois, United States
- New York, New York, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 1 year to 26 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Washington D.C., District of Columbia, United States; Chicago, Illinois, United States; New York, New York, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.