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)

Not Recruiting

Trial ID: NCT03213691


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.

Official Title

NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) - Phase 2 Subprotocol of Selumetinib (AZD6244 Hydrogen Sulfate) in Patients With Tumors Harboring Activating MAPK Pathway Mutations

Stanford Investigator(s)


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

         - 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

   - For patients with solid tumors without known bone marrow involvement:

      - Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 within 7 days prior to

      - 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

      - 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

      - 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


drug: Selumetinib Sulfate

other: Laboratory Biomarker Analysis

drug: Selumetinib

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Jennifer Marcellus

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