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NCT03213691

Selumetinib Sulfate in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)

Completed Phase 2 Results posted Last updated 5 February 2025
What this trial tests

Phase 2 trial testing Laboratory Biomarker Analysis in Advanced Malignant Solid Neoplasm in 21 participants. Completed in 31 December 2024.

Timeline
30 October 2017
Primary endpoint
30 June 2021
31 December 2024

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment21
Start date30 October 2017
Primary completion30 June 2021
Estimated completion31 December 2024
Sites110 locations across Puerto Rico, United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 12 Months to 21, any sex, with Advanced Malignant Solid Neoplasm or Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Response Rate Primary · From enrollment to the end of treatment, up to 2 years

A responder is defined as a patient who achieves a best response of partial response (PR) or complete response (CR) on the study. Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed using the Wilson score interval method. The revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to determine response and progression in this study, with specific criteria outlined for the different subtypes of tumors (e.g., 2-dimensional measurements for central nervous system (CNS) tumors

GroupValue95% CI
Treatment (Selumetinib)0
Percentage of Participants With Treatment-related Adverse Events as Accessed by Common Terminology Criteria for Adverse Events (CTCAE) Version (v) 5.0 Secondary · From enrollment to the end of treatment, up to 2 years

A patient will be counted only once for a given toxicity for the worst grade of that toxicity reported for that patient.

GroupValue95% CI
Treatment (Selumetinib)9068.3 – 98.8
Progression Free Survival (PFS) Secondary · From the initiation of protocol treatment to the occurrence of any of the following events: disease progression or disease recurrence or death from any cause, assessed up to 5 years

Progression free survival will be defined as time from the initiation of protocol treatment to the occurrence of any of the following events: disease progression or disease recurrence or death from any cause. PFS along with the confidence intervals will be estimated using the Kaplan-Meier method.

GroupValue95% CI
Treatment (Selumetinib)154.0 – 34.0

Adverse events — posted to ClinicalTrials.gov

Time frame: From enrollment to 30 days after the end of treatment, up to 2 years. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment (Selumetinib)
Serious: 12/20 (60%)
Deaths: 5/20

Serious adverse events (21 terms)

ReactionSystemTreatment (Selumetinib)
Abdominal painGastrointestinal disorders
Disease progressionGeneral disorders
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specifyNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Thromboembolic eventVascular disorders
PapilledemaEye disorders
Abdominal distensionGastrointestinal disorders
Ileal obstructionGastrointestinal disorders
Rectal painGastrointestinal disorders
VomitingGastrointestinal disorders
Death NOSGeneral disorders
Infections and infestations - Other, specifyInfections and infestations
CPK increasedInvestigations
DehydrationMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
Bone painMusculoskeletal and connective tissue disorders
Tumor painNeoplasms benign, malignant and unspecified (incl cysts and polyps)
HeadacheNervous system disorders
HydrocephalusNervous system disorders
Adult respiratory distress syndromeRespiratory, thoracic and mediastinal disorders
Surgical and medical procedures - Other, specifySurgical and medical procedures
HematomaVascular disorders
Other adverse events (119 terms — click to expand)

ReactionSystemTreatment (Selumetinib)
DiarrheaGastrointestinal disorders
AnemiaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
FatigueGeneral disorders
White blood cell decreasedInvestigations
HypokalemiaMetabolism and nutrition disorders
Rash acneiformSkin and subcutaneous tissue disorders
Neutrophil count decreasedInvestigations
HypertriglyceridemiaMetabolism and nutrition disorders
HeadacheNervous system disorders
Aspartate aminotransferase increasedInvestigations
CPK increasedInvestigations
HyperglycemiaMetabolism and nutrition disorders
HyperphosphatemiaMetabolism and nutrition disorders
HypoalbuminemiaMetabolism and nutrition disorders
HypomagnesemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
Sinus tachycardiaCardiac disorders
ConstipationGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Creatinine increasedInvestigations
Platelet count decreasedInvestigations
Blurred visionEye disorders
Abdominal painGastrointestinal disorders
VomitingGastrointestinal disorders
AnorexiaMetabolism and nutrition disorders
HypernatremiaMetabolism and nutrition disorders
HypocalcemiaMetabolism and nutrition disorders
PruritusSkin and subcutaneous tissue disorders
Eye disorders - Other, specifyEye disorders
Mucositis oralGastrointestinal disorders
Edema limbsGeneral disorders
Gait disturbanceGeneral disorders
Non-cardiac chest painGeneral disorders
Papulopustular rashInfections and infestations
Alkaline phosphatase increasedInvestigations
Blood bilirubin increasedInvestigations
Cholesterol highInvestigations
Investigations - Other, specifyInvestigations
Lymphocyte count decreasedInvestigations

Most-reported serious reactions: Abdominal pain, Disease progression, Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify, Thromboembolic event, Papilledema, Abdominal distension, Ileal obstruction, Rectal pain.

Data from ClinicalTrials.gov NCT03213691 adverse events section.

Sponsor's own description

This phase II Pediatric MATCH trial studies how well selumetinib sulfate works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with MAPK pathway activation mutations that have spread to other places in the body and have come back or do not respond to treatment. Selumetinib sulfate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeted fusion analysis can aid in the classification and treatment of pediatric glioma, ependymoma, and glioneuronal tumors.
    Lake JA, Donson AM, Prince E, Davies KD, et al · · 2020 · cited 49× · PMID 31595628 · DOI 10.1002/pbc.28028
  2. Phase II Study of Selumetinib in Children and Young Adults With Tumors Harboring Activating Mitogen-Activated Protein Kinase Pathway Genetic Alterations: Arm E of the NCI-COG Pediatric MATCH Trial.
    Eckstein OS, Allen CE, Williams PM, Roy-Chowdhuri S, et al · · 2022 · cited 45× · PMID 35363510 · DOI 10.1200/jco.21.02840
  3. A review of the biological and clinical implications of RAS-MAPK pathway alterations in neuroblastoma.
    Mlakar V, Morel E, Mlakar SJ, Ansari M, et al · · 2021 · cited 37× · PMID 34103089 · DOI 10.1186/s13046-021-01967-x
  4. Clinical Pharmacokinetics and Pharmacodynamics of Selumetinib.
    Campagne O, Yeo KK, Fangusaro J, Stewart CF. · · 2021 · cited 35× · PMID 33354735 · DOI 10.1007/s40262-020-00967-y
  5. TERT expression is susceptible to BRAF and ETS-factor inhibition in BRAF<sup>V600E</sup>/TERT promoter double-mutated glioma.
    Gabler L, Lötsch D, Kirchhofer D, van Schoonhoven S, et al · · 2019 · cited 27× · PMID 31391125 · DOI 10.1186/s40478-019-0775-6
  6. Cutting Edge Therapeutic Insights Derived from Molecular Biology of Pediatric High-Grade Glioma and Diffuse Intrinsic Pontine Glioma (DIPG).
    Bailey CP, Figueroa M, Mohiuddin S, Zaky W, et al · · 2018 · cited 13× · PMID 30340362 · DOI 10.3390/bioengineering5040088
  7. Neuroblastoma in the Era of Precision Medicine: A Clinical Review.
    Wahba A, Wolters R, Foster JH. · · 2023 · cited 9× · PMID 37835416 · DOI 10.3390/cancers15194722
  8. Targeting the Ras pathway in pediatric hematologic malignancies.
    Pikman Y, Stieglitz E. · · 2021 · cited 8× · PMID 33394740 · DOI 10.1097/mop.0000000000000981

Verify or expand the search:

Other trials of Laboratory Biomarker Analysis

Trials testing the same drug.

Other recruiting trials for Advanced Malignant Solid Neoplasm

Currently open trials in the same condition.

Other National Cancer Institute (NCI) trials

Trials by the same sponsor.

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