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Pilot Study of Tasigna®/Nilotinib (AMN107) in Neurofibromatosis (NF1) Patients With Plexiform Neurofibromas

Phase 0
18 Years
Open (Enrolling)
Neurofibromatosis, NF1, Neurofibromas

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Trial Information

Pilot Study of Tasigna®/Nilotinib (AMN107) in Neurofibromatosis (NF1) Patients With Plexiform Neurofibromas

This is an open-label Pilot Study to determine the efficacy of Tasigna® in adults with
neurofibromatosis (NF1) and plexiform neurofibromas with the secondary goals of determining
the toxicity, and tumor markers in this genetically defined population. The rationale for
this study arises from the response of human and murine NF1 cells to Tasigna® in vitro and
the clinical response in NF1 patients with plexiform neurofibromas using the similar drug,
Gleevec®. Following enrollment each subject will initially receive Tasigna orally at 200 mg
twice daily for two weeks. If tolerated, the dose will be increased to 300 mg twice daily
after a minimum of two weeks and will be increase to a maximum dose of 400mg twice daily
after an additional two weeks if tolerated. Subjects will have his/her dose increased as
tolerated dose during the first three months of therapy. The maximum targeted dose is 400mg
twice daily.

Inclusion Criteria:

1. Patients > or = 18 years of age.

2. Clinical diagnosis of neurofibromatosis type 1 (NF1)

3. Presence of clinically significant plexiform neurofibromas (tumors that are
potentially life threatening or are impinging on vital structures or significant
impairment in the quality of life from pain or other symptoms)

4. Patients must have measurable disease by magnetic resonance imaging (MRI)(as defined
by Response Evaluation Criteria in Solid Tumors, see Appendix 4)

5. Patients must have a Karnofsky Performance Status of ≥50%

6. Adequate end organ function, defined as the following:

- Creatinine < 1.5 x ULN

- ANC > 1.5 x 109/L

- Platelets > 100 x 109/L

- Total bilirubin < 1.5 x ULN

- Does not apply to patients with isolated hyperbilirubinemia (e.g., Gilbert's
disease) grade <3.

- AST (SGOT) and ALT (SGPT) < 2.5 x ULN

- Serum amylase and lipase ≤ 1.5 x ULN

- Alkaline phosphatase ≤ 2.5 x ULN

- Patients must have the following laboratory values (WNL = within normal limits
at the local institution lab) or corrected to within normal limits with
supplements prior to the first dose of study medication:

- Potassium (WNL)

- Magnesium (WNL)

- Phosphorus (WNL)

- Calcium (WNL)

Exclusion Criteria:

1. Previous treatment with any other tyrosine kinase inhibitor

2. Impaired cardiac function including any one of the following:

i. Inability to monitor the QT interval on ECG ii. Congenital long QT syndrome or a
known family history of long QT syndrome. iii. Clinically significant resting
brachycardia (<50 beats per minute) iv. QTc > 450 msec on baseline ECG. If QTc >450
msec and electrolytes are not within normal ranges, electrolytes should be corrected
and then the patient re-screened for QTc v. Myocardial infarction within 12 months
prior to starting study vi. Other clinically significant uncontrolled heart disease
(e.g. unstable angina, congestive heart failure or uncontrolled hypertension) vii.
History or presence of clinically significant ventricular or atrial tachyarrhythmias

3. Patients currently receiving treatment with strong CYP3A4 inhibitors and treatment
cannot be either discontinued or switched to a different medication prior to starting
study drug. (Appendix 1).

4. Patients currently receiving treatment with any medications that have the potential
to prolong the QT interval and the treatment cannot be either discontinued or
switched to a different medication prior to starting study drug (Appendix 3)

5. Impaired gastrointestinal (GI) function or GI disease that may significantly alter
the absorption of study drug (e.g., ulcerative diseases, uncontrolled nausea,
vomiting, diarrhea, malabsorption syndrome, small bowel resection or gastric bypass

6. Acute or chronic pancreatic disease

7. Patient has known brain metastasis. Non specific CNS changes on MRI characteristic
with NF1 are allowed.

8. Another primary malignant disease, which requires systemic treatment (chemotherapy or

9. Acute or chronic liver disease or severe renal disease considered unrelated to the

10. History of significant congenital or acquired bleeding disorder unrelated to cancer

11. Major surgery within 4 weeks prior to Day 1 of the study or who have not recovered
from prior surgery.

12. Treatment with other investigational agents within 30 days of Day 1.

13. History of non-compliance to medical regimens or inability to grant consent.

14. Female patients who are pregnant, breast feeding, or of childbearing potential
without a negative pregnancy test prior to baseline. Male or female patients of
childbearing potential unwilling to use contraceptive precautions throughout the
trial and 3 months following discontinuation of study drug. Post-menopausal women
must be amenorrheic for at least 12 months to be considered of non-childbearing
potential. Women of childbearing potential must have a negative serum pregnancy test
prior to the first dose of nilotinib.

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 Tasigna® in patients with neurofibromas (NF1) using standard RECIST criteria.

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Melissa Markel, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Indiana University


United States: Institutional Review Board

Study ID:




Start Date:

January 2011

Completion Date:

January 2017

Related Keywords:

  • Neurofibromatosis
  • NF1
  • Neurofibromas
  • NF1
  • plexiform neurofibromas
  • nilotinib
  • Tasigna
  • Neurofibroma
  • Neurofibromatoses
  • Neurofibromatosis 1
  • Osteitis Fibrosa Cystica
  • Neurofibroma, Plexiform



Riley Hospital for Children Indianapolis, Indiana  46202