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NCT03213691 · REGISTRY CONDITION SEARCH

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)

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE2
Status at capture
COMPLETED
Registry last update
2025-02-05

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Response Rate

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outcome · POSTED

Percentage of Participants With Treatment-related Adverse Events as Accessed by Common Terminology Criteria for Adverse Events (CTCAE) Version (v) 5.0

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outcome · POSTED

Progression Free Survival (PFS)

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outcome · NOT POSTED

Biomarker Analysis as Predictors of Response to Selumetinib

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outcome · NOT POSTED

Changes in Tumor Genomic Profile

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
Inclusion Criteria: * Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to molecular analysis for therapy choice (MATCH) to APEC1621E based on the presence of an actionable mutation * Note: patients with BRAF V600 actionable mutations of interest (aMOIs) will be preferentially assigned to APEC1621G (vemurafenib) if that study is open and they are otherwise eligible for it * Patients must have a body surface area \>= 0.5 m\^2 at enrollment * Patients must have radiographically measurable disease at the time of study enrollment; patients with neuroblastoma who do not have measurable disease but have iobenguane (MIBG) positive (+) evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) and visible on more than one slice * Note: the following do not qualify as measurable disease: * Malignant fluid collections (e.g., ascites, pleural effusions) * Bone marrow infiltration except that detected by MIBG scan for neuroblastoma * Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography \[PET\] scans) except as noted for neuroblastoma * Elevated tumor markers in plasma or cerebrospinal fluid (CSF) * Previously radiated lesions that have not demonstrated clear progression post radiation * Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 * Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age; Note: neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment; patients 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 * Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately * Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: \>= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea) * Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): \>= 7 days after the last dose of agent * Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1 * Corticosteroids: if used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid * Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for growth factors that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator * Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors) * Stem cell Infusions (with or without total body irradiation \[TBI\]): * Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: \>= 84 days after infusion and no evidence of graft versus host disease (GVHD) * Autologous stem cell infusion including boost infusion: \>= 42 days * Cellular therapy: \>= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer \[NK\] cells, dendritic cells, etc.) * X-ray therapy (XRT)/external beam irradiation including protons: \>= 14 days after local XRT; \>= 150 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial bone marrow (BM) radiation * Note: radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment * Radiopharmaceutical therapy (e.g., radiolabeled antibody, iodine I 131 metaiodobenzylguanidine \[131I-MIBG\]): \>= 42 days after systemically administered radiopharmaceutical therapy * Patients must not have received prior exposure to selumetinib (AZD6244 hydrogen sulfate) * For patients with solid tumors without known bone marrow involvement: * Peripheral absolute neutrophil count (ANC) \>= 1000/mm\^3 within 7 days prior to enrollment * Platelet count \>= 100,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) * Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity * Creatinine clearance or radioisotope glomerular filtration rate (GFR) within 7 days prior to enrollment \>= 70 ml/min/1.73 m\^2 or a serum creatinine based on age/gender as follows: * Age: 1 to \< 2 years; maximum serum creatinine (mg/dL): male 0.6; female 0.6 * Age: 2 to \< 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8 * Age: 6 to \< 10 years; maximum serum creatinine (mg/dL): male 1; female 1 * Age: 10 to \< 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2 * Age: 13 to \< 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4 * Age: \>= 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4 * Bilirubin (sum of conjugated + unconjugated) =\< 1.5 x upper limit of normal (ULN) for age within 7 days prior to enrollment * Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L; (for the purpose of this study, the ULN for SGPT is 45 U/L) within 7 days prior to enrollment * Serum albumin \>= 2 g/dL within 7 days prior to enrollment * Shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \>= 50% by gated radionuclide study within 7 days prior to enrollment * A blood pressure (BP) =\< the 95th percentile for age, height, and gender measured within 7 days prior to enrollment; please note that 3 serial blood pressures should be obtained and averaged to determine baseline BP; patients with hypertension controlled on antihypertensive medications will be allowed if otherwise eligible * Serum triglyceride level =\< 300 mg/dL within 7 days prior to enrollment * Serum total cholesterol level =\< 300 mg/dL within 7 days prior to enrollment * Patients must be able to swallow intact capsules whole * All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines Exclusion Criteria: * Pregnant or breast-feeding women will not be entered on this study because there is currently no available information regarding human fetal or teratogenic toxicities; pregnancy tests must be obtained in girls who are post-menarchal; females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study treatment; males with sexual partners who are pregnant or who could become pregnant (ie, women of child-bearing potential) should use effective methods of contraception for 12 weeks after completing the study to avoid pregnancy and/or potential adverse effects on the developing embryo * Concomitant medications * Corticosteroids: patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid * Investigational drugs: patients who are currently receiving another investigational drug are not eligible * Anti-cancer agents: patients who are currently receiving other anti-cancer agents are not eligible * Anti-GVHD agents post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial * CYP3A4 agents: patients who are currently receiving drugs that are strong inducers or inhibitors of CYP3A4 are not eligible; strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the end of the study * CYP2C19 agents: patients who are currently receiving drugs that are strong CYP2C19 inducers (e.g., rifampin, ritonavir) or inhibitors (e.g.., fluoxetine, fluvoxamine, ticlopidine) are not eligible * Patients who have an uncontrolled infection are not eligible * Patients with known significant ophthalmologic conditions (uncontrolled glaucoma, history of retinal vein occlusion or retinal detachment, excluding patients with longstanding findings secondary to existing conditions) are not eligible * Patients with low grade glioma are not eligible * Patients who have received a prior solid organ transplantation are not eligible * Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
healthy Volunteers
false
maximum Age
21 Years
minimum Age
12 Months
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  1. description
    Patients receive selumetinib sulfate PO BID on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
    intervention Names
    1. Other: Laboratory Biomarker Analysis
    2. Drug: Selumetinib
    3. Drug: Selumetinib Sulfate
    label
    Treatment (selumetinib)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Treatment (selumetinib)
    description
    Correlative studies
    name
    Laboratory Biomarker Analysis
    type
    OTHER
  2. arm Group Labels
    1. Treatment (selumetinib)
    description
    Given PO
    name
    Selumetinib
    other Names
    1. ARRY-142886
    2. AZD 6244
    3. AZD-6244
    4. AZD6244
    5. MEK Inhibitor AZD6244
    type
    DRUG
  3. arm Group Labels
    1. Treatment (selumetinib)
    description
    Given PO
    name
    Selumetinib Sulfate
    other Names
    1. AZD-6244 Hydrogen Sulfate
    2. AZD6244 Hydrogen Sulfate
    3. AZD6244 Hydrogen Sulphate
    4. Koselugo
    5. Selumetinib Sulphate
    type
    DRUG
Study design
allocation
NA
intervention Model
SINGLE_GROUP
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
21
type
ACTUAL
Registered outcome plans (not posted results)
other Outcomes
  1. description
    A descriptive analysis will be performed and will be summarized with simple summary statistics. All of these analyses will be descriptive in nature.
    measure
    Biomarker Analysis as Predictors of Response to Selumetinib
    time Frame
    Up to 4.5 years
  2. description
    A descriptive analysis will be performed and will be summarized with simple summary statistics. All of these analyses will be descriptive in nature.
    measure
    Changes in Tumor Genomic Profile
    time Frame
    Up to 4.5 years
primary Outcomes
  1. description
    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.
    measure
    Response Rate
    time Frame
    From enrollment to the end of treatment, up to 2 years
secondary Outcomes
  1. description
    A patient will be counted only once for a given toxicity for the worst grade of that toxicity reported for that patient.
    measure
    Percentage of Participants With Treatment-related Adverse Events as Accessed by Common Terminology Criteria for Adverse Events (CTCAE) Version (v) 5.0
    time Frame
    From enrollment to the end of treatment, up to 2 years
  2. description
    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.
    measure
    Progression Free Survival (PFS)
    time Frame
    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
Full study description
brief Summary
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.
detailed Description
PRIMARY OBJECTIVE: I. To determine the objective response rate (ORR; complete response + partial response) in pediatric patients treated with selumetinib (AZD6244 hydrogen sulfate) with advanced solid tumors (including central nervous system \[CNS\] tumors), non-Hodgkin lymphomas or histiocytic disorders that harbor activating genetic alterations in the MAPK pathway. SECONDARY OBJECTIVES: I. To estimate the progression free survival in pediatric patients treated with selumetinib (AZD6244 hydrogen sulfate) with advanced solid tumors (including CNS tumors), non-Hodgkin lymphomas or histiocytic disorders that harbor MAPK activation mutations. II. To obtain additional information about the tolerability of selumetinib (AZD6244 hydrogen sulfate) in children with relapsed or refractory cancer. EXPLORATORY OBJECTIVES: I. To evaluate other biomarkers as predictors of response to selumetinib (AZD6244 hydrogen sulfate) and specifically, whether tumors that harbor different mutations or fusions will demonstrate differential response to selumetinib (AZD6244 hydrogen sulfate) treatment. II. To explore approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid (DNA). OUTLINE: Patients receive selumetinib sulfate 25 mg/m2/dose orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.
Source references
references
  1. citation
    Eckstein OS, Allen CE, Williams PM, Roy-Chowdhuri S, Patton DR, Coffey B, Reid JM, Piao J, Saguilig L, Alonzo TA, Berg SL, Ramirez NC, Jaju A, Mhlanga J, Fox E, Hawkins DS, Mooney MM, Takebe N, Tricoli JV, Janeway KA, Seibel NL, Parsons DW. 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. J Clin Oncol. 2022 Jul 10;40(20):2235-2245. doi: 10.1200/JCO.21.02840. Epub 2022 Apr 1.
    pmid
    35363510
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Source notices and limitations
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    Preserved source evidence · Not medical advice