AZD2171 in Treating Patients With Neurofibromatosis Type 1 and Plexiform Neurofibroma and/or Neurofibroma Near the Spine
|Neurofibromatosis Type 1 Plexiform Neurofibroma Spinal Cord Neurofibroma||Drug: Cediranib Maleate||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
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|
- Proportion of Patients With Tumor Response (Complete Response [CR] or Partial Response [PR]) [ Time Frame: Baseline to end of treatment, maximum of 26 cycles (28 days/cycle). ]
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 as Measured Using Kaplan-Meier Method [ Time Frame: From registration to death (due to any cause) max 51 months ]Survival time is defined as the time from registration to death due to any cause.
- Time to Disease Progression as Measured Using Kaplan-Meier Method [ Time Frame: From registration to documentation of disease progression up to 26 cycles (28 days/cycle). ]
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 as Assessed Using the Method of Kaplan-Meier [ Time Frame: From time of confirmed tumor objective response as CR or PR to the date of progression max 51 months ]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 as Assessed Using the Method of Kaplan-Meier [ Time Frame: From the date of randomization to the date at which the patient is removed from treatment due to progression, toxicity, or refusal up to 51 months. ]
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. [ Time Frame: At baseline, prior to each subsequent course (q 28+/- 3 days), and at end of treatment up to 51 months ]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.
|Study Start Date:||May 2006|
|Primary Completion Date:||October 2011 (Final data collection date for primary outcome measure)|
Experimental: Treatment (cediranib maleate)
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.
Drug: Cediranib Maleate
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00326872
|United States, Alabama|
|University of Alabama at Birmingham Cancer Center|
|Birmingham, Alabama, United States, 35233|
|United States, District of Columbia|
|Howard University Hospital|
|Washington, District of Columbia, United States, 20060|
|United States, Illinois|
|University of Chicago Comprehensive Cancer Center|
|Chicago, Illinois, United States, 60637|
|United States, Massachusetts|
|Massachusetts General Hospital Cancer Center|
|Boston, Massachusetts, United States, 02114|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, Michigan|
|Wayne State University/Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|United States, Missouri|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|United States, Ohio|
|Case Western Reserve University|
|Cleveland, Ohio, United States, 44106|
|Principal Investigator:||Dusica Babovic-Vuksanovic||Mayo Clinic|