AZD2171 in Treating Patients With Neurofibromatosis Type 1 and Plexiform Neurofibroma and/or Neurofibroma Near the Spine
Condition: Neurofibromatosis Type 1; Plexiform Neurofibroma; Spinal Cord Neurofibroma
MeSH terms: Neurofibromatoses; Neurofibromatosis 1; Neurofibroma; Neurofibroma, Plexiform
Intervention: Cediranib Maleate
Intervention MeSH terms: Cediranib; Maleic acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well AZD2171 works in treating patients with
      neurofibromatosis type 1 and plexiform neurofibroma and/or neurofibroma near the spine.
      AZD2171 may stop the growth of tumor cells by blocking some of the enzymes needed for cell
      growth and by blocking blood flow to the tumor.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis* of neurofibromatosis type 1 (NF1) and extensive plexiform and/or paraspinal
             neurofibromasproducing pain (not controlled by use of over-the-counter medications),
             progressive neurologic deficit, or significant neurologic consequenceswith continuous
             tumor growth

               -  Extensive paraspinal neurofibroma defined as a neurofibroma that involves
                  multiple neural roots at ≥ 3 spinal levels with connection between the levels or
                  extending laterally along the nerves

                    -  Symptomatic neurofibromas at < 3 spinal levels, but surgical treatment is
                       not possible, allowed

          -  Meets ≥ 2 diagnostic criteria for NF1, including the following:

               -  Six or more café-au-lait spots (≥ 1.5 cm in postpubertal patients)

               -  Freckling in the axilla or groin

               -  Optic glioma

               -  Two or more Lisch nodules

               -  Distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia orthinning
                  of long-bone cortex)

               -  First-degree relative with NF1

          -  Patients with documented mutation in neurofibromin gene with onlysymptomatic plexiform
             and/or paraspinal neurofibroma who do not fulfill the above clinical criteria are
             eligible

          -  Measurable disease, defined as ≥ 1 lesion whose longest diameter can beaccurately
             measured as 8.0 cm^3 with 3-dimensional (3D) MRI

               -  Skin lesions are consideredmeasurable (e.g., plexiform neurofibromas), but MRI
                  imaging still required for 3D measurement

          -  Patients with symptomatic neurofibroma, in whom surgery is not feasible, who refuse
             surgery or are not goodsurgical candidates due to high risk of damage to vital
             structures or spinal cordinjury are eligible

          -  No evidence of progressive optic glioma, malignant glioma, malignant peripheralnerve
             sheath tumor, or other cancer requiring treatment with chemotherapy orradiotherapy

          -  ECOG performance status 0-3

          -  WBC ≥ 3,000/mm^3

          -  Absolute neutrophil count ≥ 1,500/mm^3

          -  Platelet count ≥ 100,000/mm^3

          -  Hemoglobin ≥ 8.0 g/dL

          -  Bilirubin normal (patients with Gilbert's syndrome allowed despite elevated bilirubin)

          -  Alkaline phosphatase normal

          -  AST and ALT ≤ 2.5 times upper limit of normal

          -  Thyroid-stimulating hormone and free thyroxin normal

          -  Creatinine normal OR creatinine clearance ≥ 60 mL/min

          -  Ejection fraction ≥ 50% by echocardiogram

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  No other uncontrolled, serious medical condition that would preclude study
             participation, including any of the following:

               -  Cardiac arrhythmia

               -  Diabetes

               -  Serious infection

               -  Significant cardiac, pulmonary, hepatic, or other organ dysfunction

          -  No psychiatric illness or social situation that would preclude study compliance

          -  No history of allergic reactions attributed to compounds of similar chemical
             orbiologic composition to AZD2171

          -  No New York Heart Association class III or IV disease

               -  Class II disease controlled with treatment and increased monitoring allowed

          -  No systolic blood pressure (BP) > 130 mm Hg and diastolic BP > 90 mm Hg

          -  No history of familial long QT syndrome

          -  Mean QTc ≤ 470 msec (with Bazett's correction) by EKG

          -  QTc prolongation ≤ 500 msec

          -  No other significant ECG abnormality within the past 14 days

          -  See Disease Characteristics

          -  More than 30 days since prior investigational agents

          -  More than 4 weeks since prior radiotherapy, chemotherapy, hormonal therapy directed at
             thetumor, immunotherapy, biologic therapy (e.g., interferon), or majorsurgery

          -  No concurrent medication that may markedly affect renal function (e.g., vancomycin,
             amphotericin, or pentamidine)

          -  No concurrent CYP interactive medications

          -  No concurrent combination antiretroviral therapy for HIV-positive patients

          -  No concurrent enzyme-inducing anticonvulsants (e.g., phenytoin, carbamazepine, or
             phenobarbital)

          -  No concurrent use of drugs or biologics with proarrhythmic potential