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Trametinib and Everolimus for Treatment of Pediatric and Young Adult Patients With Recurrent Gliomas (PNOC021)

Primary Purpose

Recurrent World Health Organization (WHO) Grade II Glioma, Low-grade Glioma, High Grade Glioma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Everolimus
Trametinib
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent World Health Organization (WHO) Grade II Glioma focused on measuring Mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), MAPK, PI3K

Eligibility Criteria

1 Year - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Participants must have histologically confirmed diagnosis of an LGG (WHO grade I-II) that is recurrent or progressive after prior treatment (biologic, chemotherapy or radiation therapy) or must have a histologically confirmed diagnosis of a high grade glioma (HGG) (WHO grade III-VI)

    • Participants with LGG who have had surgery alone are not eligible.
    • Participants with neurofibromatosis type 1 (NF-1) are eligible but must have available tissue per study requirements neurofibromatosis (NF) status will be collected
    • Participants with spinal cord primaries or disseminated disease are eligible
  • For enrollment, snap frozen tissue (150 mg) or 10 unstained 10 um formalin-fixed, paraffin-embedded (FFPE) slides for comprehensive genomic testing or results of prior testing is required

    • If clinical comprehensive testing has already been performed, the requirement for submission of tissue may be waived after discussion and review of results with study chairs
  • Participants must have evaluable disease
  • Prior therapy: Participants must have received prior therapy other than surgery and must have fully recovered from the acute toxic effects of all prior chemotherapy, biologics, immunotherapy, or radiotherapy prior to entering this study

    • Myelosuppressive chemotherapy: Participants must have received their last dose of known myelosuppressive anticancer chemotherapy at least three weeks prior to study registration or at least six weeks if they had received nitrosourea. Biologic agents: Participant must have recovered from any acute toxicity potentially related to the agent and received their last dose of the biologic agent >= 7 days prior to study registration. For biologic agents that have a prolonged half-life, at least three half-lives must have elapsed prior to registration

      • Participants may have received prior treatment with a MEK or mTOR inhibitor but must not have developed severe (grade III or IV) clinically significant toxicity. (Participants who developed grade III or IV toxicity which was not presumed by the treating physician to be medically significant should be discussed with the study chair or co-chair)
    • Monoclonal antibody treatment: Participants must have received their last dose at least four weeks prior to study registration
    • Radiation: Participants must have: had their last fraction of local irradiation to the primary tumor, craniospinal irradiation (> 24 Gy) or total body irradiation > 12 weeks prior to registration; investigators are reminded to review potentially eligible cases to confirm disease progression and avoid confusion with pseudo-progression
    • Bone marrow transplant: Participants must be: >= 6 months since allogeneic bone marrow transplant prior to registration; >= 3 months since autologous bone marrow/stem cell prior to registration
    • Corticosteroids: Participants who are receiving steroids must be on a stable or decreasing dose for at least 1 week prior to registration
  • Karnofsky >= 50 for participants > 16 years of age and Lansky >= 50 for participants =< 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
  • Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 (unsupported)
  • Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
  • Hemoglobin >= 8 m/dL (may be supported)
  • International normalized ratio (INR) =< 1.5
  • Creatinine clearance or radioisotope growth factor receptor (rGFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

    • 1 to < 2 years: 0.6 (male), 0.6 (female)
    • 2 to < 6 years: 0.8 (male), 0.8 (female)
    • 6 to < 10 years: 1 (male), 1 (female)
    • 10 to < 13 years: 1.2 (male), 1.2 (female)
    • 13 to < 16 years: 1.5 (male), 1.4 (female)
    • >= 16 years: 1.7 (male), 1.4 (female)
  • Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
  • Serum glutamate pyruvate transaminase (SGPT) alanine aminotransferase (ALT) =< 3 x ULN
  • Serum albumin >= 2 g/dL
  • Sodium, potassium, calcium and magnesium within 1.5 x institutional lower limit of normal (LLN) or ULN
  • Participants must have cholesterol level < 350 mg/dL and triglycerides < 400 mg/dL before starting therapy. In case one or both of these are exceeded, the participant can only be included after initiation of appropriate lipid lowering medication and documentation of cholesterol < 350 mg/dL and triglycerides < 400mg/dl before start of therapy
  • Participants with seizure disorder may be enrolled if well controlled. Participants must be on non-enzyme inducing anticonvulsants which are not excluded on study therapy
  • Participants with neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration
  • Corrected QT (QTc) interval =< 450 msecs
  • Left ventricular ejection fraction (LVEF) >= 50%
  • Pulse oximeter (Ox) > 93% on room air
  • Hypertension

    • Participants 3-17 years of age must have a blood pressure that is =< 95th percentile for age, height, and gender at the time of registration
    • Participants who are >= 18 years of age must have a blood pressure that is < 140/90 mm of Hg at the time of registration
  • Participants must agree to use adequate contraception: The effects of trametinib and everolimus on the developing human fetus are unknown. For this reason, women of child-bearing potential and males of child fathering potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 4 months after completion of trametinib and everolimus administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • A legal parent/guardian or participant must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate per institutional guidelines

Exclusion Criteria:

  • Participants who are receiving any other investigational agent for treatment of their tumor
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to everolimus or trametinib
  • Participants without available tissue from prior surgery. (If clinical comprehensive testing has already been performed, the requirement for submission of tissue may be waived after discussion and review of results with study chairs)
  • Participant is receiving any of the following medications within 7 days prior to enrollment (If participants require (re)initiation of these agents after enrollment and prior to start of therapy they will not be eligible to initiate study therapy):

    • Known strong inducers or inhibitors of CYP3A4/5, including enzyme inducing anti-convulsant drugs (EIACDs), grapefruit, grapefruit hybrids, pomelos, starfruit, and Seville oranges
    • Substrates of CYP3A4/5 with a narrow therapeutic index
    • Herbal preparations/medications (except for vitamins) including, but not limited to: St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, black cohosh and ginseng. Participants should stop using all herbal medications at least 7 days prior to enrollment
    • As part of the enrollment/informed consent procedures, the participant and/or legal parent or guardian will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product
  • Women of childbearing potential who are pregnant or breast-feeding

    • Female participants of childbearing potential must have a negative serum or urine pregnancy test within 72 hours of enrollment AND within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Human immunodeficiency virus (HIV) positive participants will be ineligible if HIV therapy regimen has not been stable for at least 4 weeks or there is intent to change the regimen within 8 weeks following enrollment, or if they are severely immunocompromised
  • Participants with known hepatitis B or C are not eligible
  • Participants with any clinically significant unrelated systemic illness (serious infectious or significant cardiac, pulmonary, hepatic or other organ dysfunction), which in the opinion of the investigator would interfere with the study procedures or results
  • Participants with other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) including heart failure that meets New York Heart Association (NYHA) class II or above are excluded

Sites / Locations

  • University of Alabama at Birmingham, Children's of AlabamaRecruiting
  • Children's Hospital Los AngelesRecruiting
  • University of California, San Diego Rady Children's HospitalRecruiting
  • University of California, San FranciscoRecruiting
  • Children's National Medical CenterRecruiting
  • University of FloridaRecruiting
  • Ann & Robert H. Lurie Children's Hospital of ChicagoRecruiting
  • Riley Hospital for ChildrenRecruiting
  • John Hopkins UniversityRecruiting
  • Dana Farber Cancer InstituteRecruiting
  • Children's MinnesotaRecruiting
  • Washington University in St. LouisRecruiting
  • Joseph M. Sanzari Children's Hospital at Hackensack University Medical CenterRecruiting
  • New York UniversityRecruiting
  • Doernbecher Children's Hospital Oregon Health & Science UniversityRecruiting
  • Children's Hospital of PhiladelphiaRecruiting
  • Texas Children's HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (trametinib, everolimus)

Arm Description

Patients receive dosing per their assigned dose level. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Maximum tolerated dose (MTD) of trametinib in combination with everolimus for both continuous and intermittent dosing schedules
We will employ the Bayesian optimal interval (BOIN) design to find the MTD for both continuous and intermittent dosing schedules. The BOIN design is implemented in a simple way similar to the traditional 3+3 design, but is more flexible and possesses superior operating characteristics that are comparable to those of the more complex model-based designs, such as the continual reassessment method (CRM).
Incidence of adverse events for both continuous and intermittent dosing schedules
Toxicities will be graded based on Common Terminology Criteria for Adverse Events (CTCAE) V5 .0 and followed for 30 days after last treatment or until resolution or returned to baseline values.
Dose limiting toxicities (DLTs) of the combination for both continuous and intermittent dosing schedules
Any treatment related adverse event during the first cycle of therapy that leads to a dose reduction or results in delay of treatment > 7 days or which results in the permanent cessation of therapy will be considered dose limiting.
Recommended phase 2 dose (RP2D)
The RP2D rate is selected based on isotonic regression as specified in Liu and Yuan (2015). This computation is implemented by the shiny app "BOIN" available at http://www.trialdesign.org. Specifically, select as the RP2D the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate.
Maximum Concentration (Cmax) of trametinib and everolimus
Plasma trametinib and everolimus concentration-time data will be analyzed using a classic non-compartmental approach and/or population-based compartmental methods using non-linear mixed effects modeling. Individual pharmacokinetic parameters of interest after single and repeated doses (i.e., maximum plasma concentration Cmax from 0 to 24h will be calculated from the pharmacokinetic model. Trametinib and everolimus pharmacokinetics after single dose will be compared to trametinib and everolimus pharmacokinetics after repeated doses.
Area Under the Curve (AUC) of trametinib and everolimus
Plasma trametinib and everolimus concentration-time data will be analyzed using a classic non-compartmental approach and/or population-based compartmental methods using non-linear mixed effects modeling. Individual pharmacokinetic parameters of interest after single and repeated doses (i.e., area under the curve from 0 to 24h will be calculated from the pharmacokinetic model. Trametinib and everolimus pharmacokinetics after single dose will be compared to trametinib and everolimus pharmacokinetics after repeated doses.

Secondary Outcome Measures

Full Information

First Posted
July 13, 2020
Last Updated
September 20, 2023
Sponsor
University of California, San Francisco
Collaborators
Novartis Pharmaceuticals, Pediatric Brain Tumor Foundation, The Lilabean Foundation for Pediatric Brain Cancer Research
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1. Study Identification

Unique Protocol Identification Number
NCT04485559
Brief Title
Trametinib and Everolimus for Treatment of Pediatric and Young Adult Patients With Recurrent Gliomas (PNOC021)
Official Title
PNOC021: A Phase I Trial Evaluating the Combination of Trametinib and Everolimus in Pediatric and Young Adult Patients With Recurrent Low-Grade Gliomas and High Grade Gliomas
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 9, 2020 (Actual)
Primary Completion Date
December 31, 2027 (Anticipated)
Study Completion Date
December 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Francisco
Collaborators
Novartis Pharmaceuticals, Pediatric Brain Tumor Foundation, The Lilabean Foundation for Pediatric Brain Cancer Research

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase I trial studies the side effects and best dose of trametinib and everolimus in treating pediatric and young adult patients with gliomas that have come back (recurrent). Trametinib acts by targeting a protein in cells called MEK and disrupting tumor growth. Everolimus is a drug that may block another pathway in tumor cells that can help tumors grow. Giving trametinib and everolimus may work better to treat low and high grade gliomas compared to trametinib or everolimus alone.
Detailed Description
PRIMARY OBJECTIVES: I. To estimate the recommended phase 2 dose (RP2D) of trametinib given orally in combination with everolimus in pediatric and young adult patients with gliomas. II. To describe the toxicity profile and define the dose limiting toxicities (DLTs) of the combination of trametinib and everolimus in pediatric and young adult patients with recurrent low-grade gliomas (LGG) or high grade glioma (HGG). III. To characterize the pharmacokinetic profile of trametinib and everolimus when given in combination. EXPLORATORY OBJECTIVES: I. To describe the objective response rate and the 2-year progression-free survival (PFS) of LGGs to this therapy in the context of a phase I study. II. To assess quality of life (QOL) and cognitive measures in pediatric and young adult patients with LGG or HGG. III. To identify potential predictive biomarkers to targeted therapy in pediatric and young adult patients with LGGs. IV. To assess endocrine outcomes in pediatric and young adult patients with LGGs. V. To explore magnetic resonance (MR) quantitative measures of relative cerebral blood volume, permeability and apparent diffusion coefficient within the region of hyperintensity on T2-weighted images as markers of disease response and/or progression in comparison to institutional evaluation of disease response and/or progression and quantitative measures of tumor response as determined by central review (based upon both area and volumetric measures). OUTLINE: This is a dose-escalation study. Patients receive a combination of trametinib orally (PO) and everolimus in either of two dosing scheduled (continuous and intermittent). Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, then every 6 months for 5 years from the start of therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent World Health Organization (WHO) Grade II Glioma, Low-grade Glioma, High Grade Glioma
Keywords
Mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), MAPK, PI3K

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (trametinib, everolimus)
Arm Type
Experimental
Arm Description
Patients receive dosing per their assigned dose level. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Everolimus
Other Intervention Name(s)
42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001, RAD001, Votubia, Zortress
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Trametinib
Other Intervention Name(s)
GSK1120212, JTP-74057, MEK Inhibitor GSK1120212, Mekinist
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD) of trametinib in combination with everolimus for both continuous and intermittent dosing schedules
Description
We will employ the Bayesian optimal interval (BOIN) design to find the MTD for both continuous and intermittent dosing schedules. The BOIN design is implemented in a simple way similar to the traditional 3+3 design, but is more flexible and possesses superior operating characteristics that are comparable to those of the more complex model-based designs, such as the continual reassessment method (CRM).
Time Frame
Up to 28 days
Title
Incidence of adverse events for both continuous and intermittent dosing schedules
Description
Toxicities will be graded based on Common Terminology Criteria for Adverse Events (CTCAE) V5 .0 and followed for 30 days after last treatment or until resolution or returned to baseline values.
Time Frame
Up to 30 days after the last day of treatment
Title
Dose limiting toxicities (DLTs) of the combination for both continuous and intermittent dosing schedules
Description
Any treatment related adverse event during the first cycle of therapy that leads to a dose reduction or results in delay of treatment > 7 days or which results in the permanent cessation of therapy will be considered dose limiting.
Time Frame
Up to 28 days
Title
Recommended phase 2 dose (RP2D)
Description
The RP2D rate is selected based on isotonic regression as specified in Liu and Yuan (2015). This computation is implemented by the shiny app "BOIN" available at http://www.trialdesign.org. Specifically, select as the RP2D the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate.
Time Frame
Up to 28 days
Title
Maximum Concentration (Cmax) of trametinib and everolimus
Description
Plasma trametinib and everolimus concentration-time data will be analyzed using a classic non-compartmental approach and/or population-based compartmental methods using non-linear mixed effects modeling. Individual pharmacokinetic parameters of interest after single and repeated doses (i.e., maximum plasma concentration Cmax from 0 to 24h will be calculated from the pharmacokinetic model. Trametinib and everolimus pharmacokinetics after single dose will be compared to trametinib and everolimus pharmacokinetics after repeated doses.
Time Frame
Up to 5 years
Title
Area Under the Curve (AUC) of trametinib and everolimus
Description
Plasma trametinib and everolimus concentration-time data will be analyzed using a classic non-compartmental approach and/or population-based compartmental methods using non-linear mixed effects modeling. Individual pharmacokinetic parameters of interest after single and repeated doses (i.e., area under the curve from 0 to 24h will be calculated from the pharmacokinetic model. Trametinib and everolimus pharmacokinetics after single dose will be compared to trametinib and everolimus pharmacokinetics after repeated doses.
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants must have histologically confirmed diagnosis of an LGG (WHO grade I-II) that is recurrent or progressive after prior treatment (biologic, chemotherapy or radiation therapy) or must have a histologically confirmed diagnosis of a high grade glioma (HGG) (WHO grade III-VI) Participants with LGG who have had surgery alone are not eligible. Participants with neurofibromatosis type 1 (NF-1) are eligible but must have available tissue per study requirements neurofibromatosis (NF) status will be collected Participants with spinal cord primaries or disseminated disease are eligible For enrollment, snap frozen tissue (150 mg) or 10 unstained 10 um formalin-fixed, paraffin-embedded (FFPE) slides for comprehensive genomic testing or results of prior testing is required If clinical comprehensive testing has already been performed, the requirement for submission of tissue may be waived after discussion and review of results with study chairs Participants must have evaluable disease Prior therapy: Participants must have received prior therapy other than surgery and must have fully recovered from the acute toxic effects of all prior chemotherapy, biologics, immunotherapy, or radiotherapy prior to entering this study Myelosuppressive chemotherapy: Participants must have received their last dose of known myelosuppressive anticancer chemotherapy at least three weeks prior to study registration or at least six weeks if they had received nitrosourea. Biologic agents: Participant must have recovered from any acute toxicity potentially related to the agent and received their last dose of the biologic agent >= 7 days prior to study registration. For biologic agents that have a prolonged half-life, at least three half-lives must have elapsed prior to registration Participants may have received prior treatment with a mitogen-activated extracellular signal-regulated kinase (MEK) or Mechanistic target of rapamycin (mTOR) inhibitor but must not have developed severe (grade III or IV) clinically significant toxicity. (Participants who developed grade III or IV toxicity which was not presumed by the treating physician to be medically significant should be discussed with the study chair or co-chair) Monoclonal antibody treatment: Participants must have received their last dose at least four weeks prior to study registration Radiation: Participants must have: had their last fraction of local irradiation to the primary tumor, craniospinal irradiation (> 24 Gy) or total body irradiation > 12 weeks prior to registration; investigators are reminded to review potentially eligible cases to confirm disease progression and avoid confusion with pseudo-progression Bone marrow transplant: Participants must be: >= 6 months since allogeneic bone marrow transplant prior to registration; >= 3 months since autologous bone marrow/stem cell prior to registration Corticosteroids: Participants who are receiving steroids must be on a stable or decreasing dose for at least 1 week prior to registration Karnofsky >= 50 for participants > 16 years of age and Lansky >= 50 for participants =< 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 (unsupported) Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) Hemoglobin >= 8 m/dL (may be supported) International normalized ratio (INR) =< 1.5 Creatinine clearance or radioisotope growth factor receptor (rGFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows: 1 to < 2 years: 0.6 (male), 0.6 (female) 2 to < 6 years: 0.8 (male), 0.8 (female) 6 to < 10 years: 1 (male), 1 (female) 10 to < 13 years: 1.2 (male), 1.2 (female) 13 to < 16 years: 1.5 (male), 1.4 (female) >= 16 years: 1.7 (male), 1.4 (female) Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age Serum glutamate pyruvate transaminase (SGPT) alanine aminotransferase (ALT) =< 3 x ULN Serum albumin >= 2 g/dL Sodium, potassium, calcium and magnesium within 1.5 x institutional lower limit of normal (LLN) or ULN Participants must have cholesterol level < 350 mg/dL and triglycerides < 400 mg/dL before starting therapy. In case one or both of these are exceeded, the participant can only be included after initiation of appropriate lipid lowering medication and documentation of cholesterol < 350 mg/dL and triglycerides < 400mg/dl before start of therapy Participants with seizure disorder may be enrolled if well controlled. Participants must be on non-enzyme inducing anticonvulsants which are not excluded on study therapy Participants with neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration Corrected QT (QTc) interval =< 450 msecs Left ventricular ejection fraction (LVEF) >= 50% Pulse oximeter (Ox) > 93% on room air Hypertension Participants 3-17 years of age must have a blood pressure that is =< 95th percentile for age, height, and gender at the time of registration Participants who are >= 18 years of age must have a blood pressure that is < 140/90 mm of Hg at the time of registration Participants must agree to use adequate contraception: The effects of trametinib and everolimus on the developing human fetus are unknown. For this reason, women of child-bearing potential and males of child fathering potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 4 months after completion of trametinib and everolimus administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately A legal parent/guardian or participant must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate per institutional guidelines Exclusion Criteria: Participants who are receiving any other investigational agent for treatment of their tumor History of allergic reactions attributed to compounds of similar chemical or biologic composition to everolimus or trametinib Participants without available tissue from prior surgery. (If clinical comprehensive testing has already been performed, the requirement for submission of tissue may be waived after discussion and review of results with study chairs) Participant is receiving any of the following medications within 7 days prior to enrollment (If participants require (re)initiation of these agents after enrollment and prior to start of therapy they will not be eligible to initiate study therapy): Known strong inducers or inhibitors of CYP3A4/5, including enzyme inducing anti-convulsant drugs (EIACDs), grapefruit, grapefruit hybrids, pomelos, starfruit, and Seville oranges Substrates of CYP3A4/5 with a narrow therapeutic index Herbal preparations/medications (except for vitamins) including, but not limited to: St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, black cohosh and ginseng. Participants should stop using all herbal medications at least 7 days prior to enrollment As part of the enrollment/informed consent procedures, the participant and/or legal parent or guardian will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product Women of childbearing potential who are pregnant or breast-feeding Female participants of childbearing potential must have a negative serum or urine pregnancy test within 72 hours of enrollment AND within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required Human immunodeficiency virus (HIV) positive participants will be ineligible if HIV therapy regimen has not been stable for at least 4 weeks or there is intent to change the regimen within 8 weeks following enrollment, or if they are severely immunocompromised Participants with known hepatitis B or C are not eligible Participants with any clinically significant unrelated systemic illness (serious infectious or significant cardiac, pulmonary, hepatic or other organ dysfunction), which in the opinion of the investigator would interfere with the study procedures or results Participants with other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) including heart failure that meets New York Heart Association (NYHA) class II or above are excluded
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Aubrie Dreschler
Phone
415-502-1600
Email
PNOC021@ucsf.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Sabine Mueller, MD, PhD, MAS
Phone
877-827-3222
Email
cancertrials@ucsf.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sabine Mueller
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham, Children's of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Girish Dhall, MD
Phone
205-638-9285
Email
gdhall@peds.uab.edu
First Name & Middle Initial & Last Name & Degree
Gregory Friedman, MD
Email
gfriedman@peds.uab.edu
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ashley Margol, MD
Phone
323-361-8147
Email
amargol@chla.usc.edu
First Name & Middle Initial & Last Name & Degree
Ashley Margol, MD
First Name & Middle Initial & Last Name & Degree
Tom Davidson, MD
Facility Name
University of California, San Diego Rady Children's Hospital
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jennifer Elster, MD
Email
jelster@rchsd.org
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aubrie Drechsler
Phone
415-502-1600
Email
PNOC021@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Sabine Mueller, MD, MPH
Phone
877-827-3222
Email
cancertrials@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Sabine Mueller, MD, PhD, MAS
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lindsay Kilburn, MD
Phone
202-476-5973
Email
lkilburn@cnmc.org
First Name & Middle Initial & Last Name & Degree
Lindsay Kilburn, MD
First Name & Middle Initial & Last Name & Degree
Roger Packer, MD
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610-0265
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elias Sayour, MD, PhD
Phone
352-294-8347
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Angela Waanders, MD, MPH
Phone
312-227-4873
Email
awaanders@luriechildrens.org
Facility Name
Riley Hospital for Children
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Scott Coven, DO, MPH
Phone
317-944-8784
Email
scoven@iu.edu
First Name & Middle Initial & Last Name & Degree
Scott Coven, DO, MPH
First Name & Middle Initial & Last Name & Degree
Daniel Runco, MD, MS
Facility Name
John Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kenneth Cohen, MD, MBA
Phone
410-614-5055
Email
kcohen@jhmi.edu
First Name & Middle Initial & Last Name & Degree
Eric Raabe, MD, PhD
Phone
410-502-5157
Email
eraabe2@jhmi.edu
First Name & Middle Initial & Last Name & Degree
Kenneth Cohen, MD, MBA
First Name & Middle Initial & Last Name & Degree
Eric Raabe, MD, PhD
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Susan Chi
Email
susan_chi@dfci.harvard.edu
First Name & Middle Initial & Last Name & Degree
Tabitha Cooney
Facility Name
Children's Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anne Bendel, MD
Phone
612-626-2778
Email
anne.bendel@childrensmn.org
First Name & Middle Initial & Last Name & Degree
Anne Bendel, MD
First Name & Middle Initial & Last Name & Degree
Maggie Skrypek, MD
Facility Name
Washington University in St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mohamad AbdelBaki, MD
Phone
314-454-6018
Email
Mohameda@wustl.edu
First Name & Middle Initial & Last Name & Degree
Josh Rubin, MD, PhD
Phone
314-286-2790
Email
rubin_j@wustl.edu
Facility Name
Joseph M. Sanzari Children's Hospital at Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Derek Hanson, MD
Phone
551-996-5437
Email
Derek.Hanson@HMHN.org
First Name & Middle Initial & Last Name & Degree
Katharine Offer, MD
Email
Katharine.Offer@HMHN.org
Facility Name
New York University
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sharon Gardner, MD
Phone
212-263-9913
Email
Sharon.Gardner@nyulangone.org
Facility Name
Doernbecher Children's Hospital Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matthew Miller, MD
Phone
503-494-1543
Email
milmatth@ohsu.edu
First Name & Middle Initial & Last Name & Degree
Matthew Miller, MD
First Name & Middle Initial & Last Name & Degree
Christopher Park, MD
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cassie Kline, MD, MAS
Phone
267-426-5026
Email
klinec@email.chop.edu
First Name & Middle Initial & Last Name & Degree
Cassie Kline, MD, MAS
First Name & Middle Initial & Last Name & Degree
Jane Mintrum, MD, PhD
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniela Westerhold
Phone
832-824-4552
Email
diwester@txch.org
First Name & Middle Initial & Last Name & Degree
Faryal Dina
Phone
(832) 824-4167
Email
fxdina@texaschildrens.org
First Name & Middle Initial & Last Name & Degree
Patricia Baxter, MD
First Name & Middle Initial & Last Name & Degree
Donald W Parsons, MD, PHD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Trametinib and Everolimus for Treatment of Pediatric and Young Adult Patients With Recurrent Gliomas (PNOC021)

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