Mitogen Activated Protein Kinase Kinase (MEK1/2) Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) in People With Neurofibromatosis Type 1 (NF1) Mutated Gastrointestinal Stromal Tumors (GIST)

Learn more about:
Related Clinical Trial
NFX-179 Topical Gel Treatment for Adults With Neurofibromatosis 1 (NF1) and Cutaneous Neurofibromas (cNF) Mechanism of Action of Transcranial Direct Current Stimulation in Neurofibromatosis Type 1 Study to Evaluate the Safety, Tolerability, PK Characteristics and Anti-tumor Activity of FCN-159 in Adult and Pediatric Participants With Neurofibromatosis Type 1 Evaluating Genetic Modifiers of Cutaneous Neurofibromas in Adults With Neurofibromatosis Type 1 Efficacy and Safety of Selumetinib in Adults With NF1 Who Have Symptomatic, Inoperable Plexiform Neurofibromas Systematically Assessing Changes in Plexiform Neurofibroma Related Disfigurement From Photographs of Subjects With Neurofibromatosis Type 1 on a Phase 2 Clinical Trial Pilot Randomized Control Trial of Telehealth Group for Improving Peer Relationships (PEERS) in NF1 Open Trial of Telehealth Group for Improving Peer Relationships (PEERS) in NF1 Identification of Pre-Malignant Lesions In Pediatric Patients With Neurofibromatosis Type 1 Using Novel Magnetic Resonance Imaging Techniques Paired With Artificial Intelligence A Study of Selumetinib in Chinese Paediatric and Adult Subjects With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas (PN) Innovation in the Treatment of Persistent Pain in Adults With NF1: Implementation of the iCanCope Mobile Application- Clinical Trial Antioxidant Therapy With N-acetylcysteine for Children With Neurofibromatosis Type 1 Antioxidant Therapy With N-acetylcysteine for Learning and Motor Behavior in Children With Neurofibromatosis Type 1 A Long-term Study of NPC-12G Gel in Neurofibromatosis Type I NFX-179 Topical Gel Treatment in Adults With Neurofibromatosis 1 (NF1) and Cutaneous Neurofibromas (cNF) Analysis of Data Collected From Individuals Administered Neurobehavioral Assessments Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia Comparison of Gastrointestinal Motility in Healthy Children and Children With Constipation AZD6244 Hydrogen Sulfate for Children With Nervous System Tumors Photodynamic Therapy for Benign Dermal Neurofibromas- Phase II Phase II Study of Gleevec/Imatinib Mesylate (STI-571, NCS 716051) in Neurofibromatosis (NF1) Patients With Plexiform Neurofibromas Medical Treatment of “High-Risk” Neurofibromas Fludeoxyglucose F 18 Positron Emission Tomography and Magnetic Resonance Perfusion Imaging in Patients With Neurofibromatosis 1 and Plexiform Neurofibroma Whole Body MRI to Identify Atypical Neurofibromas in Patients With NF1 Use of Topical Liquid Diclofenac Following Laser Microporation of Cutaneous Neurofibromas in Patients With NF1 Development and Validation of Patient Reported Outcome (PRO) Measures for Individuals With Neurofibromatosis 1 (NF1) and Plexiform Neurofibromas (PNs) Combination Chemotherapy in Treating Patients With Neurofibromatosis and Progressive Plexiform Neurofibromas Pilot Study of Gleevec/Imatinib Mesylate (STI-571, NSC 716051) in Neurofibromatosis (NF1) Patient With Plexiform Neurofibromas Treatment of NF1-related Plexiform Neurofibroma With Trametinib Subtle Myocardial Deformation Abnormalities in Asymptomatic Nf-1 Patients R115777 to Treat Children With Neurofibromatosis Type 1 and Progressive Plexiform Neurofibromas Use of RAD001 as Monotherapy in the Treatment of Neurofibromatosis 1 Related Internal Plexiform Neurofibromas Pirfenidone in Children and Young Adults With Neurofibromatosis Type I and Progressive Plexiform Neurofibromas Study of Tasigna®/Nilotinib (AMN107) in Neurofibromatosis (NF1) Patients With Plexiform Neurofibromas Ranibizumab for Neurofibromas Associated With Neurofibromatosis 1 AZD2171 in Treating Patients With Neurofibromatosis Type 1 and Plexiform Neurofibroma and/or Neurofibroma Near the Spine MEK 1/2 Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) in Adults With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas Study of Sutent®/Sunitinib (SU11248) in Subjects With NF-1 Plexiform Neurofibromas Neurofibromatosis Type 1 Brain Tumor Genetic Risk Acceptance and Commitment Therapy for Adolescents and Young Adults With Neurofibromatosis and Chronic Pain Phase II Study of Binimetinib in Children and Adults With NF1 Plexiform Neurofibromas Adaptation and Quality of Life Among Adults With Neurofibromatosis Type I Reliability of Functional Outcome Measures in Neurofibromatosis 1 Cabozantinib for Plexiform Neurofibromas (PN) in Subjects With NF1 in Children and Adults Medication Adherence in Children, Adolescents and Adults With Neurofibromatosis Type 1 (NF1) on Clinical Treatment Trials Targeting the Mechanisms Underlying Cutaneous Neurofibroma Formation in NF1: A Clinical Translational Approach. Sorafenib to Treat Children and Young Adults With Neurofibromatosis Type 1 and Inoperable Plexiform Neurofibromas Mitogen Activated Protein Kinase Kinase (MEK1/2) Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) in People With Neurofibromatosis Type 1 (NF1) Mutated Gastrointestinal Stromal Tumors (GIST) Quality of Friendships in Children With Neurofibromatosis Study of Disease Severity in Adults With Neurofibromatosis Type 1 (NF1) MEK Inhibitor Mirdametinib (PD-0325901) in Patients With Neurofibromatosis Type 1 Associated Plexiform Neurofibromas Interventions for Reading Disabilities in NF1 Everolimus for Treatment of Disfiguring Cutaneous Lesions in Neurofibromatosis1 CRAD001CUS232T Clinical Trial of Pirfenidone in Adult Patients With Neurofibromatosis 1 Acceptance and Commitment Training for Adolescents and Young Adults With Neurofibromatosis Type 1, Plexiform Neurofibromas, and Chronic Pain Neurobiology and Treatment of Reading Disability in NF-1 From Molecules to Cognition: Inhibitory Mechanisms in ASD and NF1 Vitamin D Supplementation for Adults With Neurofibromatosis Type 1 (NF1) Efficacy of Computerized Cognitive Training and Stimulant Medication in Neurofibromatosis Type 1 Analysis of Plasma for Diagnosis and Follow-up of Neurofibromatosis Type 1 Study About Annoucement of the Diagnosis of Neurofibromatosis 1 in de Novo Forms MicroRNAs in Patients With Neurofibromatosis Type 1 Pirfenidone in Treating Young Patients With Neurofibromatosis Type 1 and Plexiform Neurofibromas Stem Cells in NF1 Patients With Tumors of the Central Nervous System Function of the Pigment Epithelium in Patients With Type 1 Neurofibromatosis NF1-Attention: Study of Children With Neurofibromatosis Type 1 Treated by Methylphenidate Trial to Evaluate the Safety of Lovastatin in Individuals With Neurofibromatosis Type I (NF1) Internet Support Group for Parents of a Child With Neurofibromatosis Type 1 Reading Disability in Children With NF1 Multi-center Project: Spinal Abnormalities in Neurofibromatosis Type1 (NF1) Patients Functional Imaging and Reading Deficit in Children With NF1 Effects of Physical Training on Bone and Muscle Quality, Muscle Strength, and Motor Coordination in Children With NF1 Effect of Lamotrigine on Cognition in NF1 A Phase II Study of the mTOR Inhibitor Sirolimus in Neurofibromatosis Type 1 Related Plexiform Neurofibromas A Randomized Placebo-Controlled Study of Lovastatin in Children With Neurofibromatosis Type 1 Neurofibromatosis Type 1 (NF1) and Tibial Dysplasia Non-invasive Stimulation in Neurofibromatosis Type 1 Modifying Genes in Neurofibromatosis 1 Natural History and Biology of Skin Neurofibromas in Neurofibromatosis Type 1 Vision, Attention and Reading in Neurofibromatosis Type 1 (NF1) Children Neuropsychological Impairment and Quality of Life in Neurofibromatosis Type 1 Spinal Abnormalities in Neurofibromatosis Type 1 (NF1) Neurofibromatosis Type 1 Patient Registry Frameshift Peptides of Children With NF1 Prevalence of Constitutional Mismatch-repair Deficiency Among Suspected Neurofibromatosis Type 1/Legius Syndrome Children Without a Malignancy and Without a NF1 or SPRED1 Mutation How Neurofibromatosis Type 1 (NF1) Affects Schoolwork and Self-Esteem

Brief Title

Mitogen Activated Protein Kinase Kinase (MEK1/2) Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) in People With Neurofibromatosis Type 1 (NF1) Mutated Gastrointestinal Stromal Tumors (GIST)

Official Title

A Phase II Trial of the Mitogen Activated Protein Kinase Kinase (MEK1/2) Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) in Patients With Neurofibromatosis Type 1 (NF1) Mutated Gastrointestinal Stromal Tumors (GIST)

Brief Summary

      Background:

      Gastrointestinal stromal tumors (GIST) can cause serious medical problems. The only known
      treatment is surgery. But completely removing a GIST tumor with surgery is often not
      possible. Researchers want to see if a new drug, selumetinib, can help treat these tumors.

      Objective:

      To find out if selumetinib shrinks or slows the growth of GIST tumors and to see its side
      effects.

      Eligibility:

      People ages 3 and over who have one or more GIST tumors and may have neurofibromatosis type I
      (also called NF1). Their NF1 GIST has shown some growth or cannot be completely removed with
      surgery.

      Design:

      Participants will be screened with heart and eye tests and scans.

      Participants will be told what foods and medicines they cannot take during the study.
      Participants will keep a diary of the medicine they take during the study.

      Participants will take selumetinib capsules twice daily on an empty stomach for 28 days in a
      row. This is 1 cycle.

      During the cycles, participants will have study visits. These may include:

      Medical history

      Physical exam

      Blood and urine tests

      Heart tests

      Scans of their tumors

      Eye exam

      Positron emission tomography scan. They will be get radioactive glucose an IV line. They will
      lie quietly in a darkened room for 50-60 minutes then have the scan.

      Participants will answer questions about how they are feeling.

      Participants can stay in the study until they have bad side effects or their tumor grows.

      After finishing treatment, participants will be watched for side effects for 30 days.
    

Detailed Description

      BACKGROUND:

        -  Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the
           gastrointestinal tract, and traditional cytotoxic chemotherapy is not effective.
           Patients with Neurofibromatosis 1 (NF1) have an increased risk of developing GIST, and
           surgery remains the only standard treatment option for NF1-related GIST. While the
           tyrosine kinase inhibitors (TKIs) imatinib and sunitinib prolong survival in patients
           with KIT/PDGFRA mutated GIST, they have no documented efficacy in patients with NF1
           related GISTs, which lack KIT/PDGFRA mutations. Radiation therapy also seems to be
           ineffective. Therefore, new therapies are needed.

        -  Selumetinib (AZD6244 hyd sulfate), a novel orally bioavailable mitogen activated protein
           kinase inhibitor, is a specific inhibitor of MEK 1/2, which is currently undergoing
           evaluation in adults with refractory cancers, in adults and children with NF1 and
           plexiform neurofibromas (PN) and children with brain tumors. Evaluation of selumetinib
           in children and young adults with NF1 related plexiform neurofibromas (PN) has
           demonstrated activity with most patients demonstrating some PN shrinkage, and a partial
           response rate of 71%. Selumetinib has also demonstrated activity in children with NF1
           and low-grade gliomas. It is thus possible that selumetinib may mediate anti-tumor
           effects in NF1 GIST by inhibition of downstream signaling of Ras.

      OBJECTIVES:

      - To estimate the response rate (radiologic response as defined by RECIST v1.1) of
      selumetinib in children and adults with measurable NF1-mutated GIST which is unresectable,
      progressive or metastatic.

      ELIGIBILITY:

        -  Patients who are greater than or equal to 3 years of age and able to swallow capsules,
           with a histologically or cytologically confirmed measurable GIST without Kit or PDGFRA
           mutation, who have a clinical diagnosis of NF1 or a mutation of NF1 in the GIST.

        -  Patients tumors must demonstrate progression within the past 12 months or be metastatic;
           patients who do not meet this criterion will be followed, on the NF1 Natural History
           Study if appropriate; in the event that they demonstrate subsequent progression they may
           be enrolled.

        -  Patients must have adequate major organ function, adequate performance status, and
           normal LVEF by ECHO.

        -  No prior medical therapy is required; patients should have surgical resection if this is
           deemed feasible without unacceptable morbidity. Patients must meet the time requirements
           since prior therapy and have recovered from prior therapy toxicities.

        -  No prior treatment with selumetinib or another specific MEK1/2 inhibitor is permitted.

      DESIGN:

        -  Selumetinib will be administered at a starting dose of 50 mg/dose orally in patients 18
           years or older and 25 mg/m^2/dose in children < 18 years of age; drug will be given
           twice daily continuously in the absence of toxicity or disease progression, using 28-day
           cycles. The pediatric dose is the recommended phase II dose of selumetinib determined in
           a CTEP sponsored phase I trial of selumetinib for children and young adults with NF1 and
           inoperable plexiform neurofibromas, and the adult dose is equal to that used in our
           phase II study of adults with NF1 and inoperable PN. Adults will be allowed a one-time
           intrapatient dose escalation to 75mg BID provided the drug is well tolerated during the
           first cycle. Patients will be asked to co-enroll on POB protocol 10-C-0086:
           "Comprehensive Omics Analysis of Pediatric Solid Tumors and Establishment of a
           Repository for Related Biological Studies and 08-C-0079: Natural History Study and
           Longitudinal Assessment of Children, Adolescents, and Adults with Neurofibromatosis Type
           1".

        -  Patients will be monitored for toxicity and response.

        -  Response will be assessed on a regular schedule. FDG-PET will be obtained at baseline
           prior to therapy, on day 11 (+/- 3 days) to assess for early FDG-PET response
           (optional), after 3 cycles and as clinically indicated.

        -  This study will use a Simon optimal two-stage phase II design with a target response
           rate of 25%, enrolling a minimum of 7 and a maximum of 16 evaluable patients. A maximum
           accrual of 20 patients may be accrued allowing for a small number (4) of inevaluable
           patients.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Efficacy


Condition

Neoplasms, Nerve Tissue

Intervention

Selumetinib (AZD6244 hyd sulfate) 50mg/dose

Study Arms / Comparison Groups

 Arm 1
Description:  Patients > 18 years of age

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

0

Start Date

April 7, 2017

Completion Date

March 27, 2019

Primary Completion Date

March 27, 2019

Eligibility Criteria

        -  ELIGIBILITY CRITERIA:

          -  Age: greater than or equal to 3 years of age, BSA greater than or equal to 0.55 m^2,
             and able to swallow intact capsules.

          -  Diagnosis: must have either a clinical diagnosis of NF1 or a germline NF1 mutation, or
             in patients without the NF1 syndrome, demonstrate an NF1 mutation in the GIST verified
             in a CLIA certified laboratory. In patients without the NF1 syndrome, confirmation of
             the NF1 mutation in the GIST is required for enrollment.

               -  a) For a clinical diagnosis of NF1 patients must have at least two of the
                  diagnostic criteria for NF1 listed below

                    -  Six or more cafe-au-lait macules (greater or equal to 0.5cm in prepubertal
                       subjects or greater than or equal to 1.5 cm in post pubertal subjects)

                    -  Freckling in axilla or groin

                    -  A neurofibroma or plexiform neurofibroma

                    -  Optic glioma

                    -  Two or more Lisch nodules

                    -  A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or
                       thinning of long bone cortex)

                    -  A first-degree relative with NF1

          -  Patients must have a histologically or cytologically confirmed measurable GIST without
             PDGFRA or KIT mutations. GIST may be newly diagnosed or recurrent provided that it
             meets criteria for progressive or metastatic disease. Metastatic disease refers to
             disease outside the GI tract, not simply a multifocal primary tumor. Testing performed
             by the Laboratory of Pathology, NCI, unless previously conducted by a CLIA/CAP
             external laboratory; analysis will include evaluation of 4 exons of KIT (9, 11, 13,
             17) and 3 exons of PDGFRA (12, 14, 18).

          -  Measurable Disease:

               -  Patients must have measurable GIST as defined by RECIST v 1.1 as at least one
                  lesion not previously irradiated, that can be accurately measured at baseline
                  greater than or equal to 10 mm in the longest diameter (except lymph nodes which
                  must have short axis greater than or equal to 15 mm) with computed tomography
                  (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate
                  repeated measurements.

               -  Progressive disease: GIST has demonstrated progression as defined by RECIST v1.1
                  within the past 12 months. Patients whose tumors do not meet this criterion, and
                  have a diagnosis of NF1, may enroll on the NF1 Natural History study.

          -  Performance Status: ECOG less than or equal to 2 (Patients greater than or equal to 16
             years of age must have a Karnofsky performance level of greater than or equal to 70%
             (or ECOG less than or equal to 2), and children less than or equal to 16 years old
             must have a Lansky performance of greater than or equal to 70%

          -  Patients must have normal organ and marrow function as defined below:

               -  absolute neutrophil count greater than or equal to 1,000/mcL

               -  platelets greater than or equal to 100,000/mcL

               -  hemoglobin (Hgb) greater than or equal to 9.0 g/dL

               -  total bilirubin < 1.5(SqrRoot) institutional upper limit of normal

               -  AST(SGOT)/ALT(SGPT) < 3.0 (SqrRoot) institutional upper limit of normal

               -  creatinine clearance or radioisotope GFR > 60 mL/min/1.73 m^2 by either
                  Cockcroft- Gault formula or analysis normal serum creatinine based on age
                  described below:

                    -  Age (years): less than or equal to 5; Maximum Serum Creatinine (mg/dL): 0.8

                    -  Age (years): 5 or less or equal to 10; Maximum Serum Creatinine (mg/dL): 1.0

                    -  Age (years): 10 or less than or equal to 15; Maximum Serum Creatinine
                       (mg/dL): 1.2

                    -  Age (years): >15; Maximum Serum Creatinine (mg/dL): 1.5

          -  Prior Therapy: Patients will be eligible if tumor is metastatic, unresectable,
             progressive, or if complete tumor resection is not considered to be feasible without
             substantial risk or morbidity.

               -  Since there is no standard effective chemotherapy for patients with NF1 and GIST,
                  patients may be treated on this trial without having received prior medical
                  therapy directed at their GIST. Patients who have had prior GIST-directed surgery
                  may enroll provided they have measurable disease.

               -  Since selumetinib is not expected to cause substantial myelosuppression, there
                  will be no limit to number of prior myelosuppressive regimen for GIST or other
                  tumor manifestations associated with NF1.

               -  Patients who have received previous investigational agents or biologic therapy,
                  such as tipifarnib, pirfenidone, Peg-Intron, sorafenib, imatinib or other
                  targeted therapies are eligible for enrollment. At least 4 weeks must have
                  elapsed since receiving medical therapy directed at the PN and patients who
                  received previous GIST-directed therapy must either demonstrate progression as
                  defined by RECIST, or be unable to tolerate their previous therapy. Patients who
                  received effects of all prior therapy to less than or equal to grade 1 before
                  entering this study.

               -  Cytotoxic chemotherapy last dose must have been received at least 28 days prior
                  to enrollment, their last dose of biological therapy, immunomodulatory agents,
                  vaccines, differentiating agents, used to treat their cancer at least 7 days
                  prior to enrollment, their last dose of a monoclonal antibody at least 30 days
                  prior to enrollment, and their last dose of any investigational agent at least 30
                  days prior

        to enrollment.

          -  Growth factors that support platelet or white cell number or function must not have
             been administered within the 7 days prior to enrollment.

          -  At least 6 weeks must have elapsed prior to enrollment since the patient received any
             prior radiation therapy.

          -  At least 4 weeks must have elapsed since any surgeries, with evidence of good wound
             healing.

               -  The effects of selumetinib on the developing human fetus at the recommended
                  therapeutic dose are unknown. For this reason, women of child-bearing potential
                  and men must agree to use adequate contraception (hormonal or barrier method of
                  birth control; abstinence) prior to study entry, for the duration of study
                  participation, and for 4 weeks after dosing with selumetinib ceases. Women of
                  child-bearing potential must have a negative pregnancy test prior to entry.
                  Should a woman become pregnant or suspect she is pregnant while she or her
                  partner is participating in this study, the patient should inform her treating
                  physician immediately. Please note that the selumetinib

        manufacturer recommends that adequate contraception for male patients should be used for 16
        weeks post-last dose due to sperm life cycle.

          -  All patients and/or their parents or legal guardians must sign a written informed
             consent.

          -  Willingness to avoid excessive sun exposure and use adequate sunscreen protection if
             sun exposure is anticipated.

          -  Willingness to avoid the ingestion of grapefruit and Seville oranges (as well as other
             products containing these fruits, e.g. grapefruit juice or marmalade) during the
             study, as these may affect selumetinib metabolism.

          -  Although not a requirement, participants will be asked to also participate in protocol
             10-C-0086 Comprehensive Omics Analysis of Pediatric Solid Tumors and Establishment of
             a Repository for Related Biological Studies. Patients with NF1 will be asked to
             coenroll

        on the NF1 Natural History Study and 08-C-0079: Natural History Study and Longitudinal
        Assessment of Children, Adolescents, and Adults with Neurofibromatosis Type 1.

        EXCLUSION CRITERIA:

          -  Patients with evidence of another malignancy or benign tumor requiring chemotherapy or
             radiation therapy are excluded; however, those patients with a plexiform neurofibroma
             requiring treatment will be eligible as selumetinib has documented activity in
             plexiform neurofibromas.

          -  Patients with a diagnosis of NF1 and GIST who do not meet other eligibility criteria
             may enroll on the NF1 Natural History Study, and will be followed on this study.
             Should they require therapy for GIST based on evidence of progression, they may then
             enroll on study.

          -  Patients who are receiving any other investigational agents.

          -  Prior therapy with selumetinib or another specific MEK inhibitor is not permitted.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to selumetinib or other agents used in study.

          -  Previous MEK, RAS, or RAF inhibitor use.

          -  Patients who anticipate the need for surgical intervention within the first three
             cycles (3 months), as surgical intervention during the period of DLT evaluation may
             affect analysis of adherence and/or make the subject inevaluable.

          -  Patients with known brain metastases should be excluded from this clinical trial
             because of their poor prognosis and because they often develop progressive neurologic
             dysfunction that would confound the evaluation of neurologic and other adverse events.

          -  Patients with the following cardiac conditions are excluded:

               -  Uncontrolled hypertension (Adults: blood pressure [BP] of greater than or equal
                  to 150/95 despite medical support/management. Participants 18 years of age and
                  younger should have a blood pressure less than or equal to 95th percentile for
                  age, height and gender. Preexisting hypertension in adults should be controlled
                  (either with pharmacological or nonpharmacological methods) at the time of
                  enrollment.)

               -  Acute coronary syndrome within 6 months prior to starting treatment

               -  Uncontrolled angina - Canadian Cardiovascular Society grade II-IV despite medical
                  support/management

               -  Heart failure NYHA Class II or above

               -  Prior or current cardiomyopathy including but not limited to the following: Known
                  hypertrophic cardiomyopathy

               -  Known arrhythmogenic right ventricular cardiomyopathy

               -  Baseline left ventricular ejection fraction (LVEF) less than or equal to 55%

               -  Previous moderate or severe impairment of left ventricular systolic function
                  (LVEF less than 50% on echocardiography or equivalent on Multi-Gated Acquisition
                  Scan [MUGA]) even if full recovery has occurred.

               -  Severe valvular heart disease

               -  Atrial fibrillation with a ventricular rate greater than 100 bpm on ECG at rest

          -  Ophthalmological conditions as follows:

               -  Current or past history of retinal pigment epithelial detachment (RPED)/central
                  serous retinopathy (CSR) or retinal vein occlusion

               -  Intraocular pressure (IOP) greater than 21 mmHg or uncontrolled glaucoma
                  (irrespective of IOP).

               -  Evidence of optic glioma, malignant glioma, malignant peripheral nerve sheath
                  tumor,

               -  Ophthalmological findings secondary to long-standing optic pathway glioma (such
                  as visual loss, optic nerve pallor or strabismus) or long-standing orbitotemporal
                  PN (such as visual loss, strabismus) will NOT be considered a significant
                  abnormality for the purposes of the study

               -  Subjects with any other significant abnormality on ophthalmic examination
                  (performed by an ophthalmologist) should be discussed with the Study Chair for
                  potential eligibility.

          -  Inability to swallow capsules, since capsules cannot be crushed or broken.

          -  Patients with refractory nausea and vomiting, chronic gastrointestinal (GI) diseases
             (e.g., inflammatory bowel disease) or significant bowel resection that may
             significantly alter the absorption of study agent

          -  Patients receiving any medications or substances that are strong inhibitors or
             inducers of CYP 1A2, 2C8, 2C9, 2C19, 3A4/5 and UGT 1A1 and 1A3, P-glycoprotein, or
             BCRP are ineligible. Because the lists of these agents are constantly changing, it is
             important to regularly consult a frequently-updated medical reference. As part of the
             enrollment/informed consent procedures, the patient will be counseled on the risk of
             interactions with other agents, and what to do if new medications need to be
             prescribed or if the patient is considering a new over-the-counter medicine or herbal
             product.

          -  No supplementation with vitamin E is permitted because the selumetinib capsules
             contain vitamin E

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Pregnant women are excluded from this study because the effects of selumetinib on the
             developing human fetus at the recommended therapeutic dose are unknown. Because there
             is an unknown but potential risk for adverse events in nursing infants secondary to
             treatment of the mother, breastfeeding should be discontinued if the mother is treated
             with selumetinib.

          -  HIV-positive patients on combination antiretroviral therapy are ineligible because of
             the potential for pharmacokinetic interactions with selumetinib. Appropriate studies
             will be undertaken in patients receiving combination antiretroviral therapy when
             indicated.

          -  Ongoing radiation therapy, chemotherapy, hormonal therapy, immunotherapy, or biologic
             therapy directed at the tumor. Those patients with a plexiform neurofibroma requiring
             treatment will be eligible, as selumetinib has documented activity in plexiform
             neurofibromas.

          -  Patients who in the opinion of the investigator may not be able to comply with the
             safety monitoring requirements of the study.
      

Gender

All

Ages

3 Years - 99 Years

Accepts Healthy Volunteers

No

Contacts

Brigitte C Widemann, M.D., , 



Administrative Informations


NCT ID

NCT03109301

Organization ID

170084

Secondary IDs

17-C-0084

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)


Study Sponsor

Brigitte C Widemann, M.D., Principal Investigator, National Cancer Institute (NCI)


Verification Date

March 2019