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A Pilot Study of Sutent®/Sunitinib (SU11248), an Oral Multi-Targeted Tyrosine Kinase Inhibitor in Subjects With NF-1 Plexiform Neurofibromas

Phase 2
7 Years
65 Years
Open (Enrolling)
Neurofibromatosis, NF1, Plexiform Neurofibromas

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Trial Information

A Pilot Study of Sutent®/Sunitinib (SU11248), an Oral Multi-Targeted Tyrosine Kinase Inhibitor in Subjects With NF-1 Plexiform Neurofibromas

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.

Inclusion Criteria:

1. Age: patients must be ≥7 years of age and ≤65 years of age at the time of study

2. 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.

3. Disease status: Patients must have measurable disease.

4. 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.

5. Prior therapy: Patients must have fully recovered from the acute toxic effects of
all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

1. Myelosuppressive chemotherapy: Must not have received within 3 weeks of entry
onto this study.

2. Hematopoietic growth factors: At least 14 days since completion of therapy with
a growth factor.

3. 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.

4. 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.

6. Organ function requirements

a. 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:

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.

c. 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

7. 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.


Exclusion Criteria:

1. Prior anthracycline treatment. Patients previously treated with anthracyclines (any
dose) are not eligible.

2. Prior Cardiac Radiation Patients previously treated with a radiation field that
included the heart are not eligible.

3. 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.

4. Concomitant Medications

1. Growth factors(s): Growth factors that support platelet or white cell number or
function must not have been administered within the past 14 days

2. Investigational Drugs: Patients who are currently receiving another
investigational drug.

3. Anti-cancer agents: Patients who are currently receiving other anti-cancer

4. 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.

5. Anti-thrombotic and anti-platelet agents: warfarin (Coumadin), heparin, low
molecular weight heparin, aspirin, and/or ibuprofen, or other NSAIDs.

6. 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);

5. Infection: Patients who have an uncontrolled infection.

6. 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.

7. Patient size: Due to dosing limitations, patients with body surface area <0.5 m2
will be excluded from study.

8. 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

9. Patients with history of allergic reaction attributed to Sutent® or component of
Sutent® capsules.

10. Prior use of Sutent®: Patients who have previously received sunitinib are not
eligible for study.

11. Patients who in the opinion of the investigator may not be able to comply with the
safety monitoring requirements of the study.

12. 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.

13. 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)

14. Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled
diabetes, chronic renal disease, or active uncontrolled infection).

15. Patient has a known brain metastasis. Non-specific CNS changes on MRI/CT
characteristic of NF1 are allowed, but not known CNS malignancies.

16. Patient has known chronic liver disease (i.e., chronic active hepatitis, and

17. Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.

18. Patient had a major surgery within 2 weeks prior to study entry.


Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Disease response

Outcome Description:

To estimate the disease control rate (SD, PR, CR) with Sutent® in patients with neurofibromas (NF1).

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Chie-Schin Shih, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Indiana University


United States: Food and Drug Administration

Study ID:




Start Date:

March 2012

Completion Date:

August 2016

Related Keywords:

  • Neurofibromatosis
  • NF1
  • Plexiform Neurofibromas
  • NF1
  • plexiform neurofibromas
  • Sunitinib
  • Sutent®
  • Neurofibroma
  • Neurofibromatoses
  • Neurofibromatosis 1
  • Osteitis Fibrosa Cystica
  • Neurofibroma, Plexiform



Riley Hospital for Children at IU Health Indianapolis, Indiana  46202