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 Information
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
Administrative Informations
NCT ID
NCT01673009
Organization ID
0512-25
Responsible Party
Sponsor
Study Sponsor
Indiana University
Study Sponsor
, ,
Verification Date
April 2016