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

Recruiting now · Phase 1

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

In brief

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.

Key facts

Study ID

NCT04485559

Run by

University of California, San Francisco

People needed

50

Starts

2020-12-09

Expected to finish

2027-12-31

Last updated by the study team

2026-06-17

Who can join

Age: 1 and older, up to 25. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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)

You may not qualify if…

• 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

Where it is running

• University Of Texas Southwestern Medical Center — Dallas, Texas, United States (enrolling)
• Children's Hospital Los Angeles — Los Angeles, California, United States (enrolling)
• University of California, San Diego Rady Children's Hospital — San Diego, California, United States (enrolling)
• University of California, San Francisco — San Francisco, California, United States (enrolling)
• Children's National Medical Center — Washington D.C., District of Columbia, United States (enrolling)
• University of Florida — Gainesville, Florida, United States (enrolling)
• Ann & Robert H. Lurie Children's Hospital of Chicago — Chicago, Illinois, United States (enrolling)
• Riley Hospital for Children — Indianapolis, Indiana, United States (enrolling)
• John Hopkins University — Baltimore, Maryland, United States (enrolling)
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (enrolling)
• University of Alabama at Birmingham, Children's of Alabama — Birmingham, Alabama, United States (enrolling)
• Children's Minnesota — Minneapolis, Minnesota, United States (enrolling)
• Washington University in St. Louis — St Louis, Missouri, United States (enrolling)
• Joseph M. Sanzari Children's Hospital at Hackensack University Medical Center — Hackensack, New Jersey, United States (enrolling)
• New York University — New York, New York, United States (enrolling)
• Dana Farber Cancer Institute — Boston, Massachusetts, United States
• Doernbecher Children's Hospital Oregon Health & Science University — Portland, Oregon, United States

Full record on ClinicalTrials.gov

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