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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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 Summary:

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 unacceptabl
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: 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). ]

Original Primary Outcome:

Current Secondary Outcome:

• 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.

Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: May 16, 2006
Date Started: May 2006
Date Completion:
Last Updated: June 17, 2016
Last Verified: June 2016