Neoplasms

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

All Conditions

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Rare Diseases

Neurofibromatoses

Neurofibromatosis 1

Neurofibroma

Neurofibroma, Plexiform

Nerve Sheath Neoplasms

Neoplasms, Nerve Tissue

Neoplasms by Histologic Type

Syndrome

Neoplastic Syndromes, Hereditary

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Genetic Diseases, Inborn

Peripheral Nervous System Diseases

Neuromuscular Diseases

Nervous System Neoplasms

Peripheral Nervous System Neoplasms

Neurofibromatosis

Neurofibromatosis Type 1

All Drugs and Chemicals

Antineoplastic Agents

Maleic acid

Cediranib

Enzyme Inhibitors

Protein Kinase Inhibitors

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.

Cediranib Maleate

Dusica Babovic-Vuksanovic

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.

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.

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

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

Complete Response (CR): Disappearance of all target lesions.

Partial Response (PR): At least a 30% decrease in the volume of target lesions taking as reference the baseline volume.

Survival time is defined as the time from registration to death due to any cause.

Progression (PD): At least a 20% increase in the sum of volumes of target lesions taking as reference the smallest volume recorded since the treatment started or the appearance of one or more new lesions.

If a patient dies without documentation of disease progression, the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death.

Duration of response is defined for all evaluable patients who have achieved a confirmed tumor objective response as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented. Duration of response will be estimated using the method of Kaplan-Meier.

Time to treatment failure is defined to be the time from the date of randomization to the date at which the patient is removed from treatment due to progression, toxicity, or refusal. If the patient is considered to be a major treatment violation or is taken off study as a non-protocol failure, the patient will be censored on the date they are removed from treatment.

Time to treatment failure will be estimated using the method of Kaplan-Meier.

Reduction in self reported worst pain per cycle as measured by the Worst Pain scale from the North Central Cancer Treatment Group Brief Pain Inventory (short form). The worst pain scale is from 0-10 (10 is worst pain possible). The per-cycle average reduction in worst pain will be analyzed using generalized linear models to account for repeated measures within patients.

National Cancer Institute (NCI)

Patients receive 30 mg 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.

Treatment (Cediranib Maleate)

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Dr. Dusica Babovic-Vuksanovic

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

Survival Time as Measured Using Kaplan-Meier Method

Time to Disease Progression as Measured Using Kaplan-Meier Method

There was only 1 response and due to patient confidentiality we are not reporting this endpoint.

Duration of Response as Assessed Using the Method of Kaplan-Meier

Time to Treatment Failure as Assessed Using the Method of Kaplan-Meier

Reduction in Self Reported Worst Pain Per Cycle.

Overall Study

Spots Global Cancer Trial Database for spinal cord neurofibroma