Neurofibromatosis Type 1Phase 2NCT00326872
AZD2171 in Treating Patients With Neurofibromatosis Type 1 and Plexiform Neurofibroma and/or Neurofibroma Near the Spine
A Phase 2 study testing Cediranib Maleate in people with Neurofibromatosis Type 1 and Plexiform Neurofibroma, run by National Cancer Institute (NCI) at 9 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neurofibromatosis Type 1, Plexiform Neurofibroma, Spinal Cord Neurofibroma
- What is being tested?
- Cediranib Maleate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 9 sitesUnited States
- Study dates
- May 2006to 31 May 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Symptomatic neurofibromas at < 3 spinal levels, but surgical treatment is not possible, allowed
- 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
Show all 51Show fewer
- Optic glioma
- Two or more Lisch nodules
- Distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia orthinning of long-bone cortex)
- First-degree relative with NF1
- Patients with documented mutation in neurofibromin gene with onlysymptomatic 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 beaccurately measured as 8.0 cm^3 with 3-dimensional (3D) MRI
- Skin lesions are consideredmeasurable (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 goodsurgical candidates due to high risk of damage to vital structures or spinal cordinjury are eligible
- No evidence of progressive optic glioma, malignant glioma, malignant peripheralnerve sheath tumor, or other cancer requiring treatment with chemotherapy orradiotherapy
- 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 orbiologic 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
- See Disease Characteristics
- More than 30 days since prior investigational agents
- More than 4 weeks since prior radiotherapy, chemotherapy, hormonal therapy directed at thetumor, immunotherapy, biologic therapy (e.g., interferon), or majorsurgery
- 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
Who cannot join
None listed.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Case Western Reserve University
Cleveland, Ohio, 44106
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
Mayo Clinic
Rochester, Minnesota, 55905
Washington University School of Medicine
St Louis, Missouri, 63110
Howard University Hospital
Washington D.C., District of Columbia, 20060
About this study
Official title: A Phase II Study of AZD2171 in Adult Patients With Neurofibromatosis Type 1 and Extensive Plexiform and Paraspinal Neurofibromas
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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.
- Being tested
- Cediranib Maleate
- Medical subject headings
- Neurofibromatosis 1, Neurofibroma, Plexiform
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cediranib MaleateDrug
Also called AZD2171, AZD2171 Maleate, Recentin
| Study group | Role | What they receive |
|---|---|---|
| Treatment (cediranib maleate) | Experimental | 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. Receives: Drug: Cediranib Maleate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to end of treatment, maximum of 26 cycles (28 days/cycle).
Secondary outcomes (5)
Survival Time as Measured Using Kaplan-Meier Method
Survival time is defined as the time from registration to death due to any cause.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: At baseline, prior to each subsequent course (q 28+/- 3 days), and at end of treatment up to 51 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2006 (estimated)
- Study startMay 2006
- Primary completion21 Aug 2011
- Study completion31 May 2016
Why it stopped: Closed due to slow accrual prior to interim analysis.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neurofibromatosis Type 1Studies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Dusica Babovic-Vuksanovic, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00326872
- Sponsor's protocol ID
- NCI-2009-00128
- Other IDs
- NCI-2009-00128, MC047F, CDR0000475761, MC047F, 7133, N01CM17104, N01CM62205, P30CA015083
- Status last verified
- Jul 2017
- First submitted
- 16 May 2006
- Last updated
- 18 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of AZD2171 in Adult Patients With Neurofibromatosis Type 1 and Extensive Plexiform and Paraspinal Neurofibromas
- ClinicalTrials.gov ID
- NCT00326872
- Acronym / sponsor ID
- NCI-2009-00128
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Closed due to slow accrual prior to interim analysis.
- Enrolment
- 26 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- May 2006
- Primary completion
- 21 Aug 2011 (actual)
- Study completion
- 31 May 2016 (actual)
- First posted
- 17 May 2006 (estimated)
- Results
- Posted 26 Sep 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (cediranib maleate) | Experimental | Drug: Cediranib MaleatePatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (51 listed)
- 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
- Meets ≥ 2 diagnostic criteria for NF1, including the following:
- Patients with documented mutation in neurofibromin gene with onlysymptomatic 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 beaccurately measured as 8.0 cm^3 with 3-dimensional (3D) MRI
- Patients with symptomatic neurofibroma, in whom surgery is not feasible, who refuse surgery or are not goodsurgical candidates due to high risk of damage to vital structures or spinal cordinjury are eligible
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cediranib MaleateAlso: AZD2171, AZD2171 Maleate, Recentin | Drug | Treatment (cediranib maleate) |
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).
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.
5 secondary outcomes
Survival Time as Measured Using Kaplan-Meier Method
Time frame: From registration to death (due to any cause) max 51 months
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).
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
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.
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dusica Babovic-Vuksanovic principal investigator
Mayo Clinic
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cediranib Maleate in people with Neurofibromatosis Type 1 and Plexiform Neurofibroma, run by National Cancer Institute (NCI) at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 51 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Sep 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2017.