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

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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