AZD2171 in Treating Patients With Neurofibromatosis Type 1 and Plexiform Neurofibroma and/or Neurofibroma Near the Spine

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Brief Title

AZD2171 in Treating Patients With Neurofibromatosis Type 1 and Plexiform Neurofibroma and/or Neurofibroma Near the Spine

Official Title

A Phase II Study of AZD2171 in Adult Patients With Neurofibromatosis Type 1 and Extensive Plexiform and Paraspinal Neurofibromas

Brief 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.
    

Detailed Description

      PRIMARY OBJECTIVES:

      I. Assess the efficacy of AZD2171, in terms of volume change in target tumors by
      3-dimensional magnetic resonance imaging (3D MRI).

      II. Describe and define the toxicities of AZD2171 in these patients.

      SECONDARY OBJECTIVES:

      I. Assess the value of 3D MRI data analysis in evaluating plexiform or paraspinal
      neurofibromas compared to conventional 2-dimensional MRI data analysis.

      II. Assess the value of delayed contrast-enhanced MRI (DCE-MRI) in determining changes in
      vascularity of neurofibromas before and during treatment. III. Assess the quality of life of
      patients treated with AZD2171. IV. Evaluate the effect of AZD2171 on biological changes of
      human neurofibroma by comparing pre- and post-treatment specimens from patients involved in
      this trial or, alternatively, by evaluating the effect of AZD2171 on human tumor grafts in
      experimental animals.

      V. Evaluate relevant pharmacodynamic markers (circulating endothelial cells [CECs] and
      vascular endothelial growth factor-2 [VEGF2] levels) and pharmacogenetics analyses (variation
      in kdr/flk-1 and other genes) in response to AZD2171.

      OUTLINE: This is a multicenter study. Patients are stratified according to tumor location
      (peripheral vs paraspinal plexiform neurofibroma). Patients receive oral AZD2171 once daily
      on days 1-28.

      Treatment repeats every 28 days for 26 courses in the absence of disease progression or
      unacceptable toxicity. Patients with responding or stable disease may continue treatment
      beyond 26 courses in the absence of disease progression or unacceptable toxicity. Quality of
      life is assessed at baseline, prior to course 2, prior to course 4, and every 6 courses
      thereafter.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Proportion of Patients With Tumor Response (Complete Response [CR] or Partial Response [PR])

Secondary Outcome

 Survival Time as Measured Using Kaplan-Meier Method

Condition

Neurofibromatosis Type 1

Intervention

Cediranib Maleate

Study Arms / Comparison Groups

 Treatment (cediranib maleate)
Description:  Patients receive oral AZD2171 once daily on days 1-28. Treatment repeats every 28 days for 26 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease may continue treatment beyond 26 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, prior to course 2, prior to course 4, and every 6 courses thereafter.

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

26

Start Date

May 2006

Completion Date

May 31, 2016

Primary Completion Date

August 21, 2011

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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Dusica Babovic-Vuksanovic, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00326872

Organization ID

NCI-2009-00128

Secondary IDs

NCI-2009-00128

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)


Study Sponsor

Dusica Babovic-Vuksanovic, Principal Investigator, Mayo Clinic


Verification Date

July 2017