Phase II Study of Gleevec/Imatinib Mesylate (STI-571, NCS 716051) in Neurofibromatosis (NF1) Patients With Plexiform Neurofibromas

Brief Title

Phase II Study of Gleevec/Imatinib Mesylate (STI-571, NCS 716051) in Neurofibromatosis (NF1) Patients With Plexiform Neurofibromas

Official Title

Phase II Study of Gleevec/Imatinib Mesylate (STI-571, NCS 716051) in Neurofibromatosis (NF1) Patients With Plexiform Neurofibromas

Brief Summary

      THe primary objective is to estimate the response rate at 6 months to Gleevec® in patients
      with plexiform neurofibromas
    

Detailed Description

      This is an open-label Phase II Study to determine the efficacy of Gleevec® in
      neurofibromatosis (NF1) patients with 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 Gleevec®
      in vitro and the response of a single NF1 patient treated with Gleevec® for airway
      compression by a plexiform neurofibroma with a dramatic response not previously seen in NF1
      therapy. The plan of therapy will include oral dosing of Gleevec® at 440 mg/m^2/day (max 800
      mg/day) for pediatric subjects and 800 mg/day for adult patients. (with 25% dose reduction
      for significant toxicity). Treatment will continue for 6 months with an option to continue as
      long as the patient remains on study provided the patient shows benefit from treatments with
      Gleevec® and there are no safety concerns.
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Percent Change From Baseline in Tumor Volume at 6 Months

Secondary Outcome

 Serum Bioactivity

Condition

Neurofibromatosis

Intervention

Gleevec

Study Arms / Comparison Groups

 Administration of Gleevec

Description:  Gleevec® will be dosed orally 440 mg/m^2/day (max 800 mg/day) for pediatric subjects and 800 mg/day for adult patients.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

36

Start Date

May 2006

Completion Date

August 2012

Primary Completion Date

December 2011

Eligibility Criteria

        Inclusion Criteria:

          1. Patients 3-65 years of age.

          2. Diagnosis of neurofibromatosis (NF1), as outpatients.

          3. Presence of clinically significant plexiform neurofibromas (biopsy proven if possible
             with tissue blocks available); that is tumors that are potentially life threatening or
             are impinging on vital structures or significantly impair the quality of life from
             pain or other symptoms.

          4. Patients must have measurable disease by magnetic resonance imaging (MRI). Patients
             must have a Karnofsky or Lansky Performance score of > 80% and a life expectancy of >
             2 months.

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

             total bilirubin < 1.5 x ULN, SGOT and SGPT < 2.5 x UNL, creatinine < 1.5 x ULN, ANC >
             1.5 x 109/L, platelets > 100 x 109/L.

          6. Female patients of childbearing potential must have negative pregnancy test within 7
             days before initiation of study drug dosing. Postmenopausal women must be amenorrheic
             for at least 12 months to be considered of non-childbearing potential. Male and female
             patients of reproductive potential must agree to employ an effective barrier method of
             birth control throughout the study and for up to 3 months following discontinuation of
             study drug.

          7. Written, voluntary informed consent.

        Exclusion criteria:

          1. Patient has received any other investigational agents within 28 days of first day of
             study drug dosing, unless the disease is rapidly progressing.

          2. 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.

          3. 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)

          4. Female patients who are pregnant or breast-feeding.

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

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

          7. Patient has known chronic liver disease (i.e., chronic active hepatitis, and
             cirrhosis).

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

          9. Patient received chemotherapy within 4 weeks (6 weeks for nitrosourea or mitomycin-C)
             prior to study entry, unless the disease is rapidly progressing.

         10. Patient previously received radiotherapy to greater than 25 % of the bone marrow

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

         12. Patient with any significant history of non-compliance to medical regimens or with
             inability to grant reliable informed consent.
      

Gender

All

Ages

3 Years - 65 Years

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT01673009

Organization ID

0512-25

Responsible Party

Sponsor

Study Sponsor

Indiana University

Study Sponsor

, , 

Verification Date

April 2016