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