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)
Advanced Malignant Solid Neoplasm, Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma, Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma
About this trial
This is an interventional treatment trial for Advanced Malignant Solid Neoplasm
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
Sites / Locations
- Children's Hospital of Alabama
- Banner Children's at Desert
- Phoenix Childrens Hospital
- Arkansas Children's Hospital
- Kaiser Permanente Downey Medical Center
- Loma Linda University Medical Center
- Miller Children's and Women's Hospital Long Beach
- Children's Hospital Los Angeles
- Mattel Children's Hospital UCLA
- Valley Children's Hospital
- UCSF Benioff Children's Hospital Oakland
- Kaiser Permanente-Oakland
- Lucile Packard Children's Hospital Stanford University
- UCSF Medical Center-Mission Bay
- Children's Hospital Colorado
- Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
- Yale University
- Alfred I duPont Hospital for Children
- Children's National Medical Center
- University of Florida Health Science Center - Gainesville
- Nemours Children's Clinic-Jacksonville
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- Nicklaus Children's Hospital
- Arnold Palmer Hospital for Children
- Nemours Children's Hospital
- Nemours Children's Clinic - Pensacola
- Johns Hopkins All Children's Hospital
- Saint Joseph's Hospital/Children's Hospital-Tampa
- Saint Mary's Hospital
- Children's Healthcare of Atlanta - Egleston
- Memorial Health University Medical Center
- Kapiolani Medical Center for Women and Children
- Saint Luke's Cancer Institute - Boise
- Lurie Children's Hospital-Chicago
- University of Chicago Comprehensive Cancer Center
- Saint Jude Midwest Affiliate
- Riley Hospital for Children
- Blank Children's Hospital
- University of Iowa/Holden Comprehensive Cancer Center
- Norton Children's Hospital
- Children's Hospital New Orleans
- Ochsner Medical Center Jefferson
- Eastern Maine Medical Center
- Sinai Hospital of Baltimore
- Johns Hopkins University/Sidney Kimmel Cancer Center
- C S Mott Children's Hospital
- Children's Hospitals and Clinics of Minnesota - Minneapolis
- University of Minnesota/Masonic Cancer Center
- University of Mississippi Medical Center
- Children's Mercy Hospitals and Clinics
- Cardinal Glennon Children's Medical Center
- Washington University School of Medicine
- Mercy Hospital Saint Louis
- Children's Hospital and Medical Center of Omaha
- University of Nebraska Medical Center
- University Medical Center of Southern Nevada
- Alliance for Childhood Diseases/Cure 4 the Kids Foundation
- Summerlin Hospital Medical Center
- Hackensack University Medical Center
- Morristown Medical Center
- Saint Peter's University Hospital
- Roswell Park Cancer Institute
- The Steven and Alexandra Cohen Children's Medical Center of New York
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
- Memorial Sloan Kettering Cancer Center
- NYP/Weill Cornell Medical Center
- University of Rochester
- State University of New York Upstate Medical University
- Mission Hospital
- Carolinas Medical Center/Levine Cancer Institute
- Novant Health Presbyterian Medical Center
- Duke University Medical Center
- Children's Hospital Medical Center of Akron
- Cincinnati Children's Hospital Medical Center
- Cleveland Clinic Foundation
- Nationwide Children's Hospital
- Dayton Children's Hospital
- ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
- University of Oklahoma Health Sciences Center
- Legacy Emanuel Children's Hospital
- Oregon Health and Science University
- Geisinger Medical Center
- Children's Hospital of Philadelphia
- Children's Hospital of Pittsburgh of UPMC
- BI-LO Charities Children's Cancer Center
- Sanford USD Medical Center - Sioux Falls
- East Tennessee Childrens Hospital
- Saint Jude Children's Research Hospital
- Vanderbilt University/Ingram Cancer Center
- Dell Children's Medical Center of Central Texas
- Medical City Dallas Hospital
- UT Southwestern/Simmons Cancer Center-Dallas
- Cook Children's Medical Center
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
- M D Anderson Cancer Center
- Children's Hospital of San Antonio
- Methodist Children's Hospital of South Texas
- University of Texas Health Science Center at San Antonio
- Primary Children's Hospital
- University of Vermont and State Agricultural College
- Children's Hospital of The King's Daughters
- Virginia Commonwealth University/Massey Cancer Center
- Seattle Children's Hospital
- Providence Sacred Heart Medical Center and Children's Hospital
- Madigan Army Medical Center
- West Virginia University Healthcare
- University of Wisconsin Carbone Cancer Center
- Children's Hospital of Wisconsin
- San Jorge Children's Hospital
- University Pediatric Hospital
Arms of the Study
Arm 1
Experimental
Treatment (selumetinib)
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.