NeurofibromatosisPhase 2NCT01402817
Study of Sutent®/Sunitinib (SU11248) in Subjects With NF-1 Plexiform Neurofibromas
A Phase 2 study testing Sutent®/Sunitinib in people with Neurofibromatosis and NF1, run by Indiana University at 1 site in United States.
Trial summary
This is a pilot study to determine if adults and children with neurofibromatosis type 1 who have plexiform tumors given Sutent® respond to this drug therapy. Read more about this study
- Who is it for?
- Ages 3 to 65 years
- Conditions the study is for
- Neurofibromatosis, NF1, Plexiform Neurofibromas
- What is being tested?
- Sutent®/Sunitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2012to 14 Feb 2018
- 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 3 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age: patients must be ≥3 years of age and ≤65 years of age at the time of study entry
- Diagnosis: Patients must meet clinical diagnostic criteria of neurofibromatosis type 1 (NF1). Patients must have clinically significant plexiform neurofibromas (biopsy proven if possible with tissue blocks available). Clinically significant tumors are those which are potentially life threatening or are impinging on vital structures or significantly impair the quality of life from pain or other symptoms.
- Disease status: Patients must have measurable disease.
- Performance Level: Karnofsky ≥50 for patients >10 years of age and Lansky ≥50 for patients ≤10 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
- Prior therapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
- Myelosuppressive chemotherapy: Must not have received within 3 weeks of entry onto this study.
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- Hematopoietic growth factors: At least 14 days since completion of therapy with a growth factor.
- Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, the period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the principal investigator.
- XRT: ≥2 weeks for local palliative XRT (small port); ≥6 months must have elapsed if ≥50% radiation of pelvis; ≥6 weeks must have elapsed if other substantial BM radiation.
- Organ function requirements
- Adequate bone marrow function defined as i. Peripheral absolute neutrophil count (ANC) ≥1000/µL ii. Platelet count ≥100,000/ µL(transfusion independent, iii. Hemoglobin ≥8.0 gm/dL(may receive RBC transfusions) b. Adequate renal function defined as i. Creatinine clearance or radioisotope GFR ≥70 mL/min/1.73 m2 or ii. A serum creatinine based on age/gender as follows (Maximum Serum Creatinine (mg/dL)): Males: 6 to <10 years:1; 10 to <13 years: 1.2; 13 to <16 years: 1.5; >16 years 1.7. Females: 6 to <10 years:1; 10 to <13 years 1.2; 13 to <16 years: 1.4; >16 years: 1.4.
- The threshold creatinine values above were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC.
- Adequate Liver Function Defined As: i. Total bilirubin (sum of conjugated+unconjugated)≤1.5 times upper limit of normal (ULN) for age, and ii. SGPT(ALT)<2.5 upper limit of normal ULN). For the purpose of this study, the ULN for SGPT is 45 U/L iii. Serum albumin ≥2 g/dL d. Adequate cardiac function defined as: i. Shortening fraction or ejection fraction greater than the LLN (institutional norm), and ii. Corrected QT interval ≤450 msec e. Normal Pancreatic function defined as: i. Serum amylase ≤1.5xULN and ii. Serum lipase ≤1.5xULN. f. Blood pressure within the upper limit of normal defined as: i. A blood pressure (BP) ≤ 95th percentile for age, height, and gender and not receiving medication for treatment of hypertension.
- Informed Consent: All patients and/or their parents or legal guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
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Who cannot join
- Prior anthracycline treatment. Patients previously treated with anthracyclines (any dose) are not eligible.
- Prior Cardiac Radiation Patients previously treated with a radiation field that included the heart are not eligible.
- Pregnancy or Breast-Feeding Animal studies indicate an increased risk of death of pregnant female rats and rabbits exposed to Sutent®. Cleft lip and palate were observed in some fetuses exposed in utero to sunitinib. There is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are poet-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
- Concomitant Medications
- Growth factors(s): Growth factors that support platelet or white cell number or function must not have been administered within the past 14 days
- Investigational Drugs: Patients who are currently receiving another investigational drug.
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- Anti-cancer agents: Patients who are currently receiving other anti-cancer agents.
- The following CYP3A4 inducers are prohibited 12 days before the start of Sutent® and during the study with Sutent®: rifampin, rifabutin, carbamazepine, Phenobarbital, phenytoin, St. John's wort, efavirenz, and tipranavir.
- Anti-thrombotic and anti-platelet agents: warfarin (Coumadin), heparin, low molecular weight heparin, aspirin, and/or ibuprofen, or other NSAIDs.
- The following CYP3A4 inhibitors are prohibited 7 days before the start of sunitinib and during the study with sunitinib: azole antifungals (itraconazole, ketoconazole); clarithromycin, erythromycin, diltiazem, verapamil, HIV protease inhibitors (indinavir, saquinavir, ritonavir, atazanavir, nelfinavir); delavirdine.
- Infection: Patients who have an uncontrolled infection.
- Pleural-based tumors: Pediatric patients treated on a phase II trial with imatinib had a higher than expected rate of hemorrhagic pleural effusions. Sutent® inhibits two of the same receptor tyrosine kinases as imatinib, PDGFR and c-KIT. Patients with tumors involving or abutting the pleural surface will be excluded from study. Patients with pulmonary lesions should be monitored closely for the development of hemorrhagic pleural effusions.
- Patient size: Due to dosing limitations, patients with body surface area <0.5 m2 will be excluded from study.
- Patients with a pre-existing thyroid abnormality (hyper-or hypothyroidism) with unstable thyroid function will be excluded from study. For the purposes of this study, unstable thyroid function will be defined as thyroid function abnormalities requiring more than on e change in thyroid medication in the 6 months prior to study entry.
- Patients with history of allergic reaction attributed to Sutent® or component of Sutent® capsules.
- Prior use of Sutent®: Patients who have previously received sunitinib are not eligible for study.
- Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study.
- Patient is < 5 years free of another primary malignancy except if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
- Patient with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study)
- Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection).
- Patient has a known brain metastasis. Non-specific CNS changes on MRI/CT characteristic of NF1 are allowed, but not known CNS malignancies.
- Patient has known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).
- Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
- Patient had a major surgery within 2 weeks prior to study entry.
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Trial locations and contacts
1 site in 1 country.
United States1 site
Riley Hospital for Children at IU Health
Indianapolis, Indiana, 46202
About this study
Official title: A Pilot Study of Sutent®/Sunitinib (SU11248), an Oral Multi-Targeted Tyrosine Kinase Inhibitor in Subjects With NF-1 Plexiform Neurofibromas
This is a pilot study to determine if adults and children with neurofibromatosis type 1 who have plexiform tumors given Sutent® respond to this drug therapy.
Read the detailed description
This is an open-label pilot study to evaluate the efficacy of Sutent® in individuals with NF1 who have clinically significant plexiform tumors. A secondary goal of this study will be to seek to improve on current and novel tools to evaluate tumor response of plexiform tumors. The rationale for this study arises from the response of human and murine NF1 cells to Sutent® in vitro and the clinical response of individuals with NF1 using a similar drug,Gleevec®. Following enrollment adult subjects will start receiving Sutent® by month at 25mg once a day for 28 days. Subjects will then have 14 days without taking any Sutent®. If tolerated the dose will be increased to 37.5mg and 50mg with the same regimen (28 days of taking medication followed by 14 without). Children will be started on a dose of 10mg/m2/day once a day for 28 days. They will then have 14 days without taking any Sutent®. If tolerated the dose will be increased to 15mg/m2/day.
- Conditions
- Neurofibromatosis, NF1, Plexiform Neurofibromas
- Being tested
- Sutent®/Sunitinib
- Keywords
- NF1, plexiform neurofibromas, Sunitinib, Sutent®
- Medical subject headings
- Neurofibromatoses, Neurofibroma, Plexiform
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sutent®/SunitinibDrug
Upon enrollment, subjects will receive Sutent® orally. Adults (Age >18) will receive 25mg. Children will receive 10mg/m2/day. All subjects will take the daily dose for 28 days followed by a 14 day rest period. If subjects tolerate the initial dose, adults will be increased to 37.5mg and children will be increased to 15mg/m2/day. Again, subjects will take that dose for 28 days followed by a rest period of 14 days. Adults who tolerate the increase will go up to the maximum dose of 50mg. The maximum dose for children is 15mg/m2/day.
| Study group | Role | What they receive |
|---|---|---|
| Sutent®/Sunitinib | Experimental | Upon enrollment, subjects will receive Sutent® orally. Adults (Age >18) will receive 25mg. Children will receive 10mg/m2/day. All subjects will take the daily dose for 28 days followed by a 14 day rest period. If subjects tolerate the initial dose, adults will be increased to 37.5mg and children will be increased to 15mg/m2/day. Again, subjects will take that dose for 28 days followed by a rest period of 14 days. Adults who tolerate the increase will go up to the maximum dose of 50mg. The maximum dose for children is 15mg/m2/day. Receives: Drug: Sutent®/Sunitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease Response
To estimate the disease control rate (SD, PR, CR) with Sutent® in patients with neurofibromas (NF1). Tumor response criteria are determined by changes in size using all 3 dimensional measurements: width (W), transvers (T) , and length (L) measurements. Partial Response: ≥20% decrease in the sum of the products of the three perpendicular diameters of all target lesions (up to 5), taking as reference the initial baseline measurements.Stable Disease (SD): Neither sufficient decrease in the sum of the products of the three perpendicular diameters of all target lesions to qualify for PR (taking as reference the initial baseline measurements), nor sufficient increase in a single target lesions to qualify for PD, (taking as reference the smallest disease measurement since the treatment started).Progressive Disease (PD): 40% or more increase in the product of perpendicular diameters of ANY target lesion, taking as reference the smallest product observed.
Measured: 6 months
Secondary outcomes (1)
Volumetric Disease Evaluation
To determine the response rate with Sutent® in patients with plexiform neurofibromas using volumetric analysis of MRI scans
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2011 (estimated)
- Study startMar 2012
- Primary completionOct 2015
- Study completion14 Feb 2018
Why it stopped: 1 patient died of uncertain cause but possibly related to drug.
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 NeurofibromatosisStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe 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
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense, Pfizer
- Responsible party
- Principal investigator, Chie-Schin Shih, Indiana University
- Investigators
- Chie-Schin Shih, MD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01402817
- Sponsor's protocol ID
- 1104-07
- Status last verified
- Feb 2018
- First submitted
- 25 Jul 2011
- Last updated
- 14 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Sutent®/Sunitinib (SU11248), an Oral Multi-Targeted Tyrosine Kinase Inhibitor in Subjects With NF-1 Plexiform Neurofibromas
- ClinicalTrials.gov ID
- NCT01402817
- Acronym / sponsor ID
- 1104-07
- Conditions
- Neurofibromatosis, NF1, Plexiform Neurofibromas
- Keywords
- NF1, plexiform neurofibromas, Sunitinib, Sutent®
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: 1 patient died of uncertain cause but possibly related to drug.
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- United States Department of Defense, Pfizer
- Study start
- Mar 2012
- Primary completion
- Oct 2015 (actual)
- Study completion
- 14 Feb 2018 (actual)
- First posted
- 26 Jul 2011 (estimated)
- Results
- Posted 4 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a pilot study to determine if adults and children with neurofibromatosis type 1 who have plexiform tumors given Sutent® respond to this drug therapy.
Detailed description
This is an open-label pilot study to evaluate the efficacy of Sutent® in individuals with NF1 who have clinically significant plexiform tumors. A secondary goal of this study will be to seek to improve on current and novel tools to evaluate tumor response of plexiform tumors. The rationale for this study arises from the response of human and murine NF1 cells to Sutent® in vitro and the clinical response of individuals with NF1 using a similar drug,Gleevec®. Following enrollment adult subjects will start receiving Sutent® by month at 25mg once a day for 28 days. Subjects will then have 14 days without taking any Sutent®. If tolerated the dose will be increased to 37.5mg and 50mg with the same regimen (28 days of taking medication followed by 14 without). Children will be started on a dose of 10mg/m2/day once a day for 28 days. They will then have 14 days without taking any Sutent®. If tolerated the dose will be increased to 15mg/m2/day.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sutent®/Sunitinib | Experimental | Drug: Sutent®/SunitinibUpon enrollment, subjects will receive Sutent® orally. Adults (Age >18) will receive 25mg. Children will receive 10mg/m2/day. All subjects will take the daily dose for 28 days followed by a 14 day rest period. If subjects tolerate the initial dose, adults will be increased to 37.5mg and children will be increased to 15mg/m2/day. Again, subjects will take that dose for 28 days followed by a rest period of 14 days. Adults who tolerate the increase will go up to the maximum dose of 50mg. The maximum dose for children is 15mg/m2/day. |
Who may qualify
- Ages
- 3 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (15 listed)
- Age: patients must be ≥3 years of age and ≤65 years of age at the time of study entry
- Diagnosis: Patients must meet clinical diagnostic criteria of neurofibromatosis type 1 (NF1). Patients must have clinically significant plexiform neurofibromas (biopsy proven if possible with tissue blocks available). Clinically significant tumors are those which are potentially life threatening or are impinging on vital structures or significantly impair the quality of life from pain or other symptoms.
- Disease status: Patients must have measurable disease.
- Performance Level: Karnofsky ≥50 for patients >10 years of age and Lansky ≥50 for patients ≤10 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
- Prior therapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
Key exclusion criteria (25 listed)
- Prior anthracycline treatment. Patients previously treated with anthracyclines (any dose) are not eligible.
- Prior Cardiac Radiation Patients previously treated with a radiation field that included the heart are not eligible.
- Pregnancy or Breast-Feeding Animal studies indicate an increased risk of death of pregnant female rats and rabbits exposed to Sutent®. Cleft lip and palate were observed in some fetuses exposed in utero to sunitinib. There is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are poet-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
- Concomitant Medications
- Infection: Patients who have an uncontrolled infection.
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 |
|---|---|---|
| Sutent®/SunitinibUpon enrollment, subjects will receive Sutent® orally. Adults (Age >18) will receive 25mg. Children will receive 10mg/m2/day. All subjects will take the daily dose for 28 days followed by a 14 day rest period. If subjects tolerate the initial dose, adults will be increased to 37.5mg and children will be increased to 15mg/m2/day. Again, subjects will take that dose for 28 days followed by a rest period of 14 days. Adults who tolerate the increase will go up to the maximum dose of 50mg. The maximum dose for children is 15mg/m2/day. | Drug | Sutent®/Sunitinib |
Primary outcome
Disease Response
Time frame: 6 months
To estimate the disease control rate (SD, PR, CR) with Sutent® in patients with neurofibromas (NF1). Tumor response criteria are determined by changes in size using all 3 dimensional measurements: width (W), transvers (T) , and length (L) measurements. Partial Response: ≥20% decrease in the sum of the products of the three perpendicular diameters of all target lesions (up to 5), taking as reference the initial baseline measurements.Stable Disease (SD): Neither sufficient decrease in the sum of the products of the three perpendicular diameters of all target lesions to qualify for PR (taking as reference the initial baseline measurements), nor sufficient increase in a single target lesions to qualify for PD, (taking as reference the smallest disease measurement since the treatment started).Progressive Disease (PD): 40% or more increase in the product of perpendicular diameters of ANY target lesion, taking as reference the smallest product observed.
1 secondary outcome
Volumetric Disease Evaluation
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2018.
- 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.
Chie-Schin Shih, MD principal investigator
Indiana University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sutent®/Sunitinib in people with Neurofibromatosis and NF1, run by Indiana University at 1 site 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 15 inclusion and 25 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 14 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 4 May 2016). 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?
Disease Response (time frame: 6 months). 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 14 Mar 2018.