A Phase 2 interventional study of Cediranib Maleate in Neurofibromatosis Type 1, Plexiform Neurofibroma and Spinal Cord Neurofibroma, sponsored by National Cancer Institute (NCI). Terminated at 9 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-08-18.
Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment
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.
186 studies on the registry are indexed under Neurofibromatoses; 24 are open to participants now.
This study's enrollment of 26 is close to the median of 26 across 120 interventional studies indexed under Neurofibromatoses.
Browse Neurofibromatoses studies →National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.
Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.
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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
Meets ≥ 2 diagnostic criteria for NF1, including the following:
Measurable disease, defined as ≥ 1 lesion whose longest diameter can beaccurately measured as 8.0 cm\^3 with 3-dimensional (3D) MRI
No other uncontrolled, serious medical condition that would preclude study participation, including any of the following:
No New York Heart Association class III or IV disease
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
Also known as: AZD2171, AZD2171 Maleate, Recentin
Proportion of Patients With Tumor Response (Complete Response [CR] or Partial Response [PR])
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.
Time frame: Baseline to end of treatment, maximum of 26 cycles (28 days/cycle).
Survival Time as Measured Using Kaplan-Meier Method
Survival time is defined as the time from registration to death due to any cause.
Time frame: From registration to death (due to any cause) max 51 months
Time to Disease Progression as Measured Using Kaplan-Meier Method
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.
Time frame: From registration to documentation of disease progression up to 26 cycles (28 days/cycle).
Duration of Response as Assessed Using the Method of Kaplan-Meier
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 frame: From time of confirmed tumor objective response as CR or PR to the date of progression max 51 months
Time to Treatment Failure as Assessed 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.
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.
Reduction in Self Reported Worst Pain Per Cycle.
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.
Time frame: At baseline, prior to each subsequent course (q 28+/- 3 days), and at end of treatment up to 51 months
From 8/29/2006 until 7/31/2009, 26 patients were accrued.
| Milestone | Treatment (Cediranib Maleate) |
|---|---|
| Started | 26 |
| Completed | 26 |
| Not completed | 0 |
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.
| Proportion of patients | Treatment (Cediranib Maleate) |
|---|---|
| Proportion of Patients With Tumor Response (Complete Response [CR] or Partial Response [PR]) | 0.0384 (0.002 to 0.216) |
Survival time is defined as the time from registration to death due to any cause.
| Months | Treatment (Cediranib Maleate) |
|---|---|
| Survival Time as Measured Using Kaplan-Meier Method | NA (NA to NA) |
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.
| Months | Treatment (Cediranib Maleate) |
|---|---|
| Time to Disease Progression as Measured Using Kaplan-Meier Method | 49.15 (45.76 to NA) |
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.
No measurements were reported for this outcome.
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.
| Months | Treatment (Cediranib Maleate) |
|---|---|
| Time to Treatment Failure as Assessed Using the Method of Kaplan-Meier | 5.9 (2.6 to 42.3) |
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.
| units on a scale of 0-10 | Treatment (Cediranib Maleate) |
|---|---|
| Reduction in Self Reported Worst Pain Per Cycle. | 0.137 ± 0.0552 |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treatment (Cediranib Maleate) | — | 12/26 (46.2%) | 26/26 (100%) |
| Event | Treatment (Cediranib Maleate) |
|---|---|
| Alanine aminotransferase increasedInvestigations | 4/26 |
| Aspartate aminotransferase increasedInvestigations | 3/26 |
| Blood bilirubin increasedInvestigations | 3/26 |
| Left ventricular failureCardiac disorders | 2/26 |
| Neutrophil count decreasedInvestigations | 2/26 |
| Blood disorderBlood and lymphatic system disorders | 1/26 |
| PericarditisCardiac disorders | 1/26 |
| EsophagitisGastrointestinal disorders | 1/26 |
| Weight lossInvestigations | 1/26 |
| Depressed level of consciousnessNervous system disorders | 1/26 |
| Event | Treatment (Cediranib Maleate) |
|---|---|
| DiarrheaGastrointestinal disorders | 23/26 |
| FatigueGeneral disorders | 16/26 |
| HeadacheNervous system disorders | 14/26 |
| Blood glucose increasedMetabolism and nutrition disorders | 13/26 |
| NauseaGastrointestinal disorders | 12/26 |
| Weight lossInvestigations | 11/26 |
| HypertensionVascular disorders | 11/26 |
| ProteinuriaRenal and urinary disorders | 10/26 |
| Hand-and-foot syndromeSkin and subcutaneous tissue disorders | 10/26 |
| VomitingGastrointestinal disorders | 9/26 |
| Age, Continuous(years) | Treatment (Cediranib Maleate) |
|---|---|
| Median | 34 (19 to 52) |
| Sex: Female, Male(Participants) | Treatment (Cediranib Maleate) |
|---|---|
| Female | 13 |
| Male | 13 |
| Region of Enrollment(participants) | Treatment (Cediranib Maleate) |
|---|---|
| United States | 26 |
This study is terminated, as verified in Jul 2017. You cannot join it, but the record below documents what was studied.
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