Brief Title
Study of Tasigna®/Nilotinib (AMN107) in Neurofibromatosis (NF1) Patients With Plexiform Neurofibromas
Official Title
Pilot Study of Tasigna®/Nilotinib (AMN107) in Neurofibromatosis (NF1) Patients With Plexiform Neurofibromas
Brief Summary
The purpose of this Pilot Study is to determine if NF1 patients with plexiform neurofibromas
treated with Tasgina® respond to therapy.
Detailed Description
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.
Study Phase
Early Phase 1
Study Type
Interventional
Primary Outcome
Disease Response
Condition
Neurofibromatosis
Intervention
Tasigna
Study Arms / Comparison Groups
Tasigna
Description: Following enrollment each subject will initially receive the drug 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
6
Start Date
January 2011
Completion Date
October 2016
Primary Completion Date
July 2016
Eligibility Criteria
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 surgery).
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
radiation)
9. Acute or chronic liver disease or severe renal disease considered unrelated to the
cancer.
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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Melissa Markel, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01275586
Organization ID
1008-06
Secondary IDs
CAMN107YUS29T
Responsible Party
Sponsor
Study Sponsor
Indiana University
Collaborators
Novartis
Study Sponsor
Melissa Markel, MD, Study Chair, Indiana University
Verification Date
April 2017