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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT03213691
Other study ID # NCI-2017-01250
Secondary ID NCI-2017-01250AP
Status Active, not recruiting
Phase Phase 2
First received
Last updated
Start date October 30, 2017
Est. completion date September 22, 2024

Study information

Verified date March 2024
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 21
Est. completion date September 22, 2024
Est. primary completion date June 30, 2021
Accepts healthy volunteers No
Gender All
Age group 12 Months to 21 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Other:
Laboratory Biomarker Analysis
Correlative studies
Drug:
Selumetinib
Given PO
Selumetinib Sulfate
Given PO

Locations

Country Name City State
Puerto Rico San Jorge Children's Hospital San Juan
Puerto Rico University Pediatric Hospital San Juan
United States Children's Hospital Medical Center of Akron Akron Ohio
United States C S Mott Children's Hospital Ann Arbor Michigan
United States Mission Hospital Asheville North Carolina
United States Children's Healthcare of Atlanta - Egleston Atlanta Georgia
United States Children's Hospital Colorado Aurora Colorado
United States Dell Children's Medical Center of Central Texas Austin Texas
United States Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore Maryland
United States Sinai Hospital of Baltimore Baltimore Maryland
United States Eastern Maine Medical Center Bangor Maine
United States Children's Hospital of Alabama Birmingham Alabama
United States Saint Luke's Cancer Institute - Boise Boise Idaho
United States Roswell Park Cancer Institute Buffalo New York
United States University of Vermont and State Agricultural College Burlington Vermont
United States Carolinas Medical Center/Levine Cancer Institute Charlotte North Carolina
United States Novant Health Presbyterian Medical Center Charlotte North Carolina
United States Lurie Children's Hospital-Chicago Chicago Illinois
United States University of Chicago Comprehensive Cancer Center Chicago Illinois
United States Cincinnati Children's Hospital Medical Center Cincinnati Ohio
United States Cleveland Clinic Foundation Cleveland Ohio
United States Nationwide Children's Hospital Columbus Ohio
United States Medical City Dallas Hospital Dallas Texas
United States UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas
United States Geisinger Medical Center Danville Pennsylvania
United States Dayton Children's Hospital Dayton Ohio
United States Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center Denver Colorado
United States Blank Children's Hospital Des Moines Iowa
United States Kaiser Permanente Downey Medical Center Downey California
United States Duke University Medical Center Durham North Carolina
United States Cook Children's Medical Center Fort Worth Texas
United States University of Florida Health Science Center - Gainesville Gainesville Florida
United States BI-LO Charities Children's Cancer Center Greenville South Carolina
United States Hackensack University Medical Center Hackensack New Jersey
United States Kapiolani Medical Center for Women and Children Honolulu Hawaii
United States Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center Houston Texas
United States M D Anderson Cancer Center Houston Texas
United States Riley Hospital for Children Indianapolis Indiana
United States University of Iowa/Holden Comprehensive Cancer Center Iowa City Iowa
United States University of Mississippi Medical Center Jackson Mississippi
United States Nemours Children's Clinic-Jacksonville Jacksonville Florida
United States Children's Mercy Hospitals and Clinics Kansas City Missouri
United States East Tennessee Childrens Hospital Knoxville Tennessee
United States Alliance for Childhood Diseases/Cure 4 the Kids Foundation Las Vegas Nevada
United States Summerlin Hospital Medical Center Las Vegas Nevada
United States University Medical Center of Southern Nevada Las Vegas Nevada
United States Arkansas Children's Hospital Little Rock Arkansas
United States Loma Linda University Medical Center Loma Linda California
United States Miller Children's and Women's Hospital Long Beach Long Beach California
United States Children's Hospital Los Angeles Los Angeles California
United States Mattel Children's Hospital UCLA Los Angeles California
United States Norton Children's Hospital Louisville Kentucky
United States Valley Children's Hospital Madera California
United States University of Wisconsin Carbone Cancer Center - University Hospital Madison Wisconsin
United States Saint Jude Children's Research Hospital Memphis Tennessee
United States Banner Children's at Desert Mesa Arizona
United States Nicklaus Children's Hospital Miami Florida
United States University of Miami Miller School of Medicine-Sylvester Cancer Center Miami Florida
United States Children's Hospital of Wisconsin Milwaukee Wisconsin
United States Children's Hospitals and Clinics of Minnesota - Minneapolis Minneapolis Minnesota
United States University of Minnesota/Masonic Cancer Center Minneapolis Minnesota
United States West Virginia University Healthcare Morgantown West Virginia
United States Morristown Medical Center Morristown New Jersey
United States Vanderbilt University/Ingram Cancer Center Nashville Tennessee
United States Saint Peter's University Hospital New Brunswick New Jersey
United States Yale University New Haven Connecticut
United States The Steven and Alexandra Cohen Children's Medical Center of New York New Hyde Park New York
United States Children's Hospital New Orleans New Orleans Louisiana
United States Ochsner Medical Center Jefferson New Orleans Louisiana
United States Laura and Isaac Perlmutter Cancer Center at NYU Langone New York New York
United States Memorial Sloan Kettering Cancer Center New York New York
United States NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center New York New York
United States NYP/Weill Cornell Medical Center New York New York
United States Children's Hospital of The King's Daughters Norfolk Virginia
United States Kaiser Permanente-Oakland Oakland California
United States UCSF Benioff Children's Hospital Oakland Oakland California
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
United States Children's Hospital and Medical Center of Omaha Omaha Nebraska
United States University of Nebraska Medical Center Omaha Nebraska
United States Arnold Palmer Hospital for Children Orlando Florida
United States Nemours Children's Hospital Orlando Florida
United States Lucile Packard Children's Hospital Stanford University Palo Alto California
United States Nemours Children's Clinic - Pensacola Pensacola Florida
United States Saint Jude Midwest Affiliate Peoria Illinois
United States Children's Hospital of Philadelphia Philadelphia Pennsylvania
United States Phoenix Childrens Hospital Phoenix Arizona
United States Children's Hospital of Pittsburgh of UPMC Pittsburgh Pennsylvania
United States Legacy Emanuel Children's Hospital Portland Oregon
United States Oregon Health and Science University Portland Oregon
United States Virginia Commonwealth University/Massey Cancer Center Richmond Virginia
United States University of Rochester Rochester New York
United States Cardinal Glennon Children's Medical Center Saint Louis Missouri
United States Mercy Hospital Saint Louis Saint Louis Missouri
United States Washington University School of Medicine Saint Louis Missouri
United States Johns Hopkins All Children's Hospital Saint Petersburg Florida
United States Primary Children's Hospital Salt Lake City Utah
United States Children's Hospital of San Antonio San Antonio Texas
United States Methodist Children's Hospital of South Texas San Antonio Texas
United States University of Texas Health Science Center at San Antonio San Antonio Texas
United States UCSF Medical Center-Mission Bay San Francisco California
United States Memorial Health University Medical Center Savannah Georgia
United States Seattle Children's Hospital Seattle Washington
United States Sanford USD Medical Center - Sioux Falls Sioux Falls South Dakota
United States Providence Sacred Heart Medical Center and Children's Hospital Spokane Washington
United States State University of New York Upstate Medical University Syracuse New York
United States Madigan Army Medical Center Tacoma Washington
United States Saint Joseph's Hospital/Children's Hospital-Tampa Tampa Florida
United States ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital Toledo Ohio
United States Children's National Medical Center Washington District of Columbia
United States Saint Mary's Hospital West Palm Beach Florida
United States Alfred I duPont Hospital for Children Wilmington Delaware

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type Measure Description Time frame Safety issue
Other Biomarker Analysis as Predictors of Response to Selumetinib A descriptive analysis will be performed and will be summarized with simple summary statistics. All of these analyses will be descriptive in nature. Up to 4.5 years
Other Changes in Tumor Genomic Profile A descriptive analysis will be performed and will be summarized with simple summary statistics. All of these analyses will be descriptive in nature. Up to 4.5 years
Primary Response Rate 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. From enrollment to the end of treatment, up to 2 years
Secondary Percentage of Participants With Treatment-related Adverse Events as Accessed by Common Terminology Criteria for Adverse Events (CTCAE) Version (v) 5.0 A patient will be counted only once for a given toxicity for the worst grade of that toxicity reported for that patient. From enrollment to the end of treatment, up to 2 years
Secondary Progression Free Survival (PFS) 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. 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
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