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

NCT01089101 | Active Not Recruiting Phase 1

• 6 other identifiers: NCI-2012-03173PBTC-029BCDR667932PBTC-029U01CA081457UM1CA081457
• Study Type: interventional
• Target: 217
• Locations: 1 country
• Sites: 17

Brief Summary

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.

Conditions

Low Grade Glioma; Recurrent Childhood Pilocytic Astrocytoma; Recurrent Neurofibromatosis Type 1; Recurrent Visual Pathway Glioma; Refractory Neurofibromatosis Type 1; Refractory Visual Pathway Glioma

Outcome Measures

Primary Outcomes (4)

• Maximum tolerated dose and recommended phase 2 dose of selumetinib determined by dose-limiting toxicities (phase I)

  Toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

  28 days

• Stratum-specific objective response (complete response + partial response) rate sustained for 8 weeks (phase II)

  For each stratum separately exact confidence interval estimates will be provided for the true, unknown rates of objective response. In addition, the confirmed sustained objective response rate observed during treatment by cumulative incidence functions will be estimated. This provides not only an overall estimate of the response rate but also an estimate of the timing of responses as a function of number of months of treatment.

  40 weeks

• Objective response (objective response = complete response + partial response) (re-treatment study)

  Exact confidence interval estimates will be provided.

  Up to 48 weeks

• Disease stabilization rates (re-treatment study)

  Disease stabilization rates will be measured.

  At 1 year

Secondary Outcomes (4)

• Plasma drug concentrations and pharmacokinetic parameters (Phase I)

  Day 1 of cycle 1

• Stratum-specific progression-free survival distribution (PFS) (phase II)

  From the date of initial treatment to the earliest date of disease progression, second malignancy or death for subjects who fail; and to the date of last contact for subjects who remain at risk for failure assessed for up to 30 days

• Presence or absence of BRAF V600E mutations or BRAF KIAA1549 fusion (phase II)

  Up to 30 days

• Progression-free survival (retreatment study)

  From the date of re-treatment initiation to the earliest date of disease progression, second malignancy or death for patients who fail; and the last contact for patients who remain at risk for failure, assessed up to 30 days

Study Arms (1)

Treatment (selumetinib)

EXPERIMENTAL

Patients receive selumetinib PO BID on days 1-28. Cycles repeat every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. Patients who experience a sustained objective response from selumetinib on the phase I or phase II portions of the trial, and who have completed 2 years of treatment and stopped study drug may be enrolled on the re-treatment study after progression/recurrence. Patients in the re-treatment study may continue treatment indefinitely in the absence of disease progression or unacceptable toxicities. Patients undergo blood sample collection on study.

Procedure: Biospecimen Collection; Drug: Selumetinib

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (selumetinib)

Selumetinib DRUG

Given PO

Also known as: ARRY-142886, AZD 6244, AZD-6244, AZD6244, MEK Inhibitor AZD6244

Treatment (selumetinib)

Eligibility Criteria

• Age: 3 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (17)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, 94304, United States

Location

UCSF Medical Center-Mount Zion

San Francisco, California, 94115, United States

Location

UCSF Medical Center-Parnassus

San Francisco, California, 94143, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, 30329, United States

Location

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

Location

Children's Memorial Outpatient Center in Lincoln Park

Chicago, Illinois, 60614, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Fangusaro J, Onar-Thomas A, Young Poussaint T, Wu S, Ligon AH, Lindeman N, Banerjee A, Packer RJ, Kilburn LB, Goldman S, Pollack IF, Qaddoumi I, Jakacki RI, Fisher PG, Dhall G, Baxter P, Kreissman SG, Stewart CF, Jones DTW, Pfister SM, Vezina G, Stern JS, Panigrahy A, Patay Z, Tamrazi B, Jones JY, Haque SS, Enterline DS, Cha S, Fisher MJ, Doyle LA, Smith M, Dunkel IJ, Fouladi M. Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial. Lancet Oncol. 2019 Jul;20(7):1011-1022. doi: 10.1016/S1470-2045(19)30277-3. Epub 2019 May 28.

  PMID: 31151904 DERIVED

MeSH Terms

Conditions

Astrocytoma; Neurofibromatosis 1

Interventions

Specimen Handling; AZD 6244

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Jason R Fangusaro

  Pediatric Brain Tumor Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2010
• First Posted: March 18, 2010
• Study Start: July 7, 2010
• Primary Completion: January 17, 2026
• Study Completion (Estimated): March 18, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-03

Locations

US (17)