Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma

Running, not enrolling · Phase 1/Phase 2

Conditions studied: Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma, Recurrent Neurofibromatosis Type 1, Recurrent Visual Pathway Glioma, Refractory Neurofibromatosis Type 1, Refractory Visual Pathway Glioma

In brief

This phase I/II trial studies the side effects and the best dose of selumetinib and how well it works in treating or re-treating young patients with low grade glioma that has come back (recurrent) or does not respond to treatment (refractory). Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Key facts

Study ID

NCT01089101

Run by

National Cancer Institute (NCI)

People needed

217

Starts

2010-07-07

Expected to finish

2027-03-18

Last updated by the study team

2026-05-13

Who can join

Age: 3 and older, up to 21. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Imaging evaluations necessary to establish eligibility for study entry must be done within three (3) weeks prior to registration
• All other evaluations necessary to establish eligibility for study entry must be done within two (2) weeks prior to registration
• Patients must start therapy within 7 calendar days of registration
• Laboratory values must be no older than seven (7) days prior to the start of therapy; if a test that is repeated after registration and prior to therapy is outside the limits for eligibility, it must be rechecked within 48 hours prior to the start of therapy; if laboratory values still fail to meet eligibility criteria, the patient may not receive protocol therapy
• All patients must meet the following inclusion and exclusion criteria; NO EXCEPTIONS WILL BE GIVEN
• Participant is willing to sign a screening consent and provide adequate pre-trial tumor material for BRAF testing (both for BRAF V\^600E mutation and BRAF KIAA1549 fusion assessments)
• All patients who are candidates for enrollment in stratum 5 based on their tumor histology must be pre-screened
• Screening may be applied to potential stratum 1 and 2 patients
• Patients whose prior BRAF testing was performed at another lab (Clinical Laboratory Improvement Amendments [CLIA]/College of American Pathologist [CAP] certified or otherwise) must send additional tumor material to Brigham and Women's Hospital (BWH) for confirmation; however, to preserve available tumor material, patients whose tumor material has previously undergone BRAF analysis at the Lindeman and Ligon Labs at Brigham and Women's Hospital using the same procedures as described in this protocol, will not be required to submit additional tumor material for analysis; these patients must have both the BRAFV600E mutation and BRAF KIAA1549 fusion assessments done and if only one test was previously conducted; additional tissue will be required for the second test
• Patient must be >= 3 but =< 21 years of age at registration
• Patient must have one of the following:
• For stratum 5: non NF-1 associated low grade glioma (LGG) (other than pilocytic astrocytoma or optic pathway glioma)
• For stratum 1 or 2: non NF-1, non-optic pathway pilocytic astrocytoma; note: all patients with non NF-1 associated optic pathway glioma with or without tissue must be enrolled on stratum 4
• Patients with sporadic (non NF-1 associated), histologically diagnosed progressive, recurrent or refractory non-optic pathway pilocytic astrocytoma who have pre- treatment tumor tissue available for BRAF analysis
• NF-1 patients with radiographic evidence of a progressive, recurrent or refractory low grade glioma, with or without pre-treatment tumor tissue
• Patients with progressive, recurrent or refractory optic pathway glioma, with or without pre-treatment tumor tissue
• Patients with histologically diagnosed progressive, recurrent or refractory non NF-1 associated LGG (other than pilocytic astrocytoma or optic pathway glioma); these patients must have BRAF aberrations as documented by the Lindeman and Ligon Labs at Brigham and Women's Hospital using the same procedures
• Patients will be assigned to one of 6 strata prior to enrollment; all BRAF assessments used for stratification below must be done at the Lindeman and Ligon Labs at Brigham and Women's Hospital using the same procedures as described in this protocol; assessments for both BRAF V\^600E mutation and BRAF KIAA1549 fusion are required for patients who will enroll on strata 1, 2 and 5
• Stratum 1: patients with non NF-1 associated progressive, recurrent or refractory pilocytic astrocytoma with pre-trial tumor material available and with a BRAF aberration i.e. BRAFV\^600E mutation and/or BRAF KIAA1549 fusion as determined by IHC and FISH, respectively; patients with optic pathway glioma are excluded
• Stratum 2: patients with non NF-1 associated progressive, recurrent or refractory pilocytic astrocytoma with pre-trial tumor material available and without a BRAF aberration i.e. BRAF\^V600E mutation and/or BRAF KIAA1549 fusion as determined by IHC and FISH, respectively; patients with optic pathway glioma are excluded
• Stratum 3: patients with neuro-fibromatosis 1 (NF-1) associated progressive, recurrent or refractory low grade glioma (World Health Organization [WHO] grade I \& II), with or without tissue
• Stratum 4*: patients with non-NF1 associated progressive, recurrent or refractory optic pathway glioma with or without tissue available for BRAF evaluation
• Stratum 5: patients with non NF-1 associated progressive, recurrent or refractory low grade glioma other than pilocytic astrocytoma or optic pathway glioma with a documented BRAF aberration identified in pre-trial tumor material
• Stratum 6: patients with non-NF-1 associated progressive, recurrent or refractory low grade glioma (other than optic pathway glioma [OPG]) with tissue available for BRAF analyses who cannot be classified into stratum 1, 2 or 5 due to inadequate tissue quality, assay failure, etc
• Clarification: Stratum 4 was specifically designed for patients with hypothalamic/optic pathway gliomas; the intent is that if there is any optic chiasm invasion regardless of where the tumor is originating from (chiasm vs. hypothalamus vs. other location), the patient should be enrolled on Stratum 4, regardless of whether the tumor has been biopsied or not; obviously, there are some tumors that include part of the hypothalamus and clearly do NOT include the chiasm at all; in these situations, and if the tumor is a biopsy proven pilocytic astrocytoma, these patients should be enrolled on Stratum 1 or 2 (depending upon BRAF status)

You may not qualify if…

• Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), likely interfere with the study procedures or results
• Patients taken off treatment for progressive disease on PBTC-029 or PBTC-029B
• Patients who are receiving any other anticancer or investigational agents
• Patients with uncontrolled seizures
• Previous mitogen-activated protein kinase (MEK) inhibitor use such as PD-0325901; CI1040; AS73026; GDC 0973; ARRY43182; GSK110212
• Prior treatment with a BRAF inhibitor such as vemurafenib or dabrafenib (previous treatment with sorafenib is allowed)
• Patients 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) that meets New York Heart Association (NYHA) class II or above
• Required use of a concomitant medication that can prolong the QT interval
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD6244
• Patients previously treated with a MEK inhibitor other than AZD6244

Where it is running

• Children's Hospital Los Angeles — Los Angeles, California, United States
• Lucile Packard Children's Hospital Stanford University — Palo Alto, California, United States
• UCSF Medical Center-Mount Zion — San Francisco, California, United States
• UCSF Medical Center-Parnassus — San Francisco, California, United States
• Children's Hospital Colorado — Aurora, Colorado, United States
• Children's National Medical Center — Washington D.C., District of Columbia, United States
• Children's Healthcare of Atlanta - Arthur M Blank Hospital — Atlanta, Georgia, United States
• Lurie Children's Hospital-Chicago — Chicago, Illinois, United States
• Children's Memorial Outpatient Center in Lincoln Park — Chicago, Illinois, United States
• National Institutes of Health Clinical Center — Bethesda, Maryland, United States
• Memorial Sloan Kettering Cancer Center — New York, New York, United States
• Duke University Medical Center — Durham, North Carolina, United States
• Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States
• Children's Hospital of Pittsburgh of UPMC — Pittsburgh, Pennsylvania, United States
• Saint Jude Children's Research Hospital — Memphis, Tennessee, United States
• Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center — Houston, Texas, United States
• Texas Children's Hospital — Houston, Texas, United States

Full record on ClinicalTrials.gov

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