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

Sponsor:	Mayo Clinic
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00326872

Purpose

RATIONALE: 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.

PURPOSE: 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.

Condition	Intervention	Phase
Neurofibromatosis Type 1 Nonmalignant Neoplasm Precancerous Condition	Drug: cediranib maleate	Phase II

Study Type:	Interventional
Study Design:	Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II Study of AZD2171 in Adult Patients With Neurofibromatosis Type 1 and Extensive Plexiform and Paraspinal Neurofibromas

Resource links provided by NLM:

Genetics Home Reference related topics: neurofibromatosis type 1 neurofibromatosis type 2 Help Me Understand Genetics

MedlinePlus related topics: Cancer Neurofibromatosis

Drug Information available for: Cediranib

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Proportion of confirmed tumor response (complete or partial response) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Toxicity as measured by NCI CTCAE v4.0 [ Designated as safety issue: Yes ]
Survival time as measured by Kaplan-Meier [ Designated as safety issue: No ]
Time to disease progression as measured by Kaplan-Meier [ Designated as safety issue: No ]
Duration of response as measured by Kaplan-Meier [ Designated as safety issue: No ]
Time to treatment failure due to progression, toxicity, or refusal as measured by Kaplan-Meier [ Designated as safety issue: Yes ]
Relationship between 3-D MRI measurements and 2-D MRI measurements as measured by linear regression, Pearson's correlation coefficient, and Bland-Altman approach [ Designated as safety issue: No ]
Tumor objective response determined by 3D MRI and conventional 2-D MRI as measured by Kappa statistic [ Designated as safety issue: No ]
Quality of life (QOL) as measured by the Brief Pain Inventory, Brief Fatigue Inventory, and North Central Cancer Treatment Group Supplemental QOL Questionnaire [ Designated as safety issue: No ]
Biological changes in pre- and post-treatment human and/or mouse xenograft tumor tissue as measured by immunostaining for CD34, CD31, and vascular endothelial growth factor (VEGF) [ Designated as safety issue: No ]
Correlation of biological changes in pre- and post-treatment tumor tissue with tumor objective response, imaging measures (tumor volume, delayed contrast-enhanced MRI [DCE-MRI]), and QOL [ Designated as safety issue: No ]
Levels of VEGF and soluble FLT(sFLT) measured as surrogate markers of angiogenesis [ Designated as safety issue: No ]
Correlation of serum vs tumor VEGF [ Designated as safety issue: No ]
Effect of AZD2171 on VEGF serum levels as measured at baseline and every 4 weeks during treatment [ Designated as safety issue: No ]
Correlation of VEGF serum levels with response, time to progression, and survival [ Designated as safety issue: No ]
Correlation of circulating endothelial cells with clinical response and with other angiogenic biomarkers [ Designated as safety issue: No ]
Pharmacogenetics analyses (variation in kdr/flk-1 and other genes) at 6 months after completion of study treatment [ Designated as safety issue: No ]

Estimated Enrollment:	65
Study Start Date:	May 2006
Estimated Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Assess the efficacy of AZD2171, in terms of volume change in target tumors by 3-dimensional (3D) MRI in patients with neurofibromatosis type 1 and extensive plexiform and/or paraspinal neurofibromas.
Describe and define the toxicities of AZD2171 in these patients.

Secondary

Assess the value of 3D MRI data analysis in evaluating plexiform or paraspinal neurofibromas compared to conventional 2-dimensional MRI data analysis.
Assess the value of delayed contrast-enhanced MR imaging in determining changes in vascularity of neurofibromas before and during treatment.
Assess the quality of life of patients treated with AZD2171.
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.
Evaluate relevant pharmacodynamic markers (circulating endothelial cells 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.

PROJECTED ACCRUAL: A total of 65 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis* of neurofibromatosis type 1 (NF1) and extensive plexiform and/or paraspinal neurofibromas producing pain (not controlled by use of over-the-counter medications), progressive neurologic deficit, or significant neurologic consequences with 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 NOTE: * Histologic confirmation of tumor not required in the presence of consistent clinical and radiographic findings
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 or thinning of long-bone cortex)
- First-degree relative with NF1
Patients with documented mutation in neurofibromin gene with only symptomatic 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 be accurately measured as 8.0 cm^3 with 3-dimensional (3D) MRI
- Skin lesions are considered measurable (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 good surgical candidates due to high risk of damage to vital structures or spinal cord injury are eligible
No evidence of progressive optic glioma, malignant glioma, malignant peripheral nerve sheath tumor, or other cancer requiring treatment with chemotherapy or radiotherapy

PATIENT CHARACTERISTICS:

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 or biologic 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

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
More than 30 days since prior investigational agents
More than 4 weeks since prior radiotherapy, chemotherapy, hormonal therapy directed at the tumor, immunotherapy, biologic therapy (e.g., interferon), or major surgery
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00326872

Locations

United States, Alabama
UAB Comprehensive Cancer Center	Recruiting
Birmingham, Alabama, United States, 35294
Contact: Clinical Trials Office - UAB Comprehensive Cancer Center 205-934-0309
United States, District of Columbia
Howard University Cancer Center	Recruiting
Washington, District of Columbia, United States, 20060
Contact: Clinical Trials Office - Howard University Cancer Center 202-806-9122
United States, Illinois
University of Chicago Cancer Research Center	Recruiting
Chicago, Illinois, United States, 60637-1470
Contact: Clinical Trials Office - University of Chicago Cancer Research 773-834-7424
United States, Massachusetts
Massachusetts General Hospital	Recruiting
Boston, Massachusetts, United States, 02114
Contact: Clinical Trials Office - Massachusetts General Hospital 877-726-5130
United States, Michigan
Barbara Ann Karmanos Cancer Institute	Recruiting
Detroit, Michigan, United States, 48201-1379
Contact: Clinical Trials Office - Barbara Ann Karmanos Cancer Institute 313-576-9363
United States, Minnesota
Mayo Clinic Cancer Center	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Office - All Mayo Clinic Locations 507-538-7623
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Recruiting
Saint Louis, Missouri, United States, 63110-4803
Contact: Gerald P. Linette, MD, PhD 314-747-7222
United States, Ohio
Case Comprehensive Cancer Center	Recruiting
Cleveland, Ohio, United States, 44106-5065
Contact: Clinical Trials Office - Case Comprehensive Cancer Center 800-641-2422

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

Study Chair:

Dusica Babovic-Vuksanovic, MD

Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Charles Erlichman, Mayo Clinic Cancer Center
ClinicalTrials.gov Identifier:	NCT00326872 History of Changes
Other Study ID Numbers:	CDR0000475761, MAYO-MC047F, NCI-7133
Study First Received:	May 16, 2006
Last Updated:	August 31, 2010
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

neurofibromatosis type 1
plexiform neurofibroma
spinal cord neurofibroma

Additional relevant MeSH terms:

Neoplasms
Disease
Neurofibroma
Neurofibromatosis 1
Osteitis Fibrosa Cystica
Precancerous Conditions
Neurofibromatoses
Neurofibroma, Plexiform
Pathologic Processes
Nerve Sheath Neoplasms
Neoplasms, Nerve Tissue
Neoplasms by Histologic Type
Peripheral Nervous System Neoplasms

Nervous System Neoplasms
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Neoplastic Syndromes, Hereditary
Neurocutaneous Syndromes
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Bone Diseases, Endocrine
Bone Diseases
Musculoskeletal Diseases

ClinicalTrials.gov processed this record on February 12, 2012