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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Indiana University
ClinicalTrials.gov Identifier:
NCT01673009
First received: August 22, 2012
Last updated: August 24, 2012
Last verified: August 2012

August 22, 2012
August 24, 2012
May 2006
December 2011   (final data collection date for primary outcome measure)
Tumor Response [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Tumor response will be evaluated using the RECIST criteria.
Same as current
Complete list of historical versions of study NCT01673009 on ClinicalTrials.gov Archive Site
Serum bioactivity [ Time Frame: 7 days and 1 month ] [ Designated as safety issue: No ]
The investigators will quantitate the biologic activity of patient serum on fibroblast proliferation, migration, and collagen synthesis pre and post-Gleevec (7 days and 1 month)
Same as current
Not Provided
Not Provided
 
Phase II Study of Gleevec/Imatinib Mesylate (STI-571, NCS 716051) in Neurofibromatosis (NF1) Patients With Plexiform Neurofibromas
Phase II Study of Gleevec/Imatinib Mesylate (STI-571, NCS 716051) in Neurofibromatosis (NF1) Patients With Plexiform Neurofibromas

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

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/m2/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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Neurofibromatosis
Drug: Gleevec
Gleevec® will be dosed orally 440 mg/m2/day (max 800 mg/day) for pediatric subjects and 800 mg/day for adult patients.
Experimental: Administration of Gleevec
Gleevec® will be dosed orally 440 mg/m2/day (max 800 mg/day) for pediatric subjects and 800 mg/day for adult patients.
Intervention: Drug: Gleevec
Robertson KA, Nalepa G, Yang FC, Bowers DC, Ho CY, Hutchins GD, Croop JM, Vik TA, Denne SC, Parada LF, Hingtgen CM, Walsh LE, Yu M, Pradhan KR, Edwards-Brown MK, Cohen MD, Fletcher JW, Travers JB, Staser KW, Lee MW, Sherman MR, Davis CJ, Miller LC, Ingram DA, Clapp DW. Imatinib mesylate for plexiform neurofibromas in patients with neurofibromatosis type 1: a phase 2 trial. Lancet Oncol. 2012 Dec;13(12):1218-24. doi: 10.1016/S1470-2045(12)70414-X. Epub 2012 Oct 23. PubMed PMID: 23099009.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
36
August 2012
December 2011   (final data collection date for primary outcome measure)

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.
Both
3 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01673009
0512-25
Yes
Indiana University
Indiana University
Not Provided
Not Provided
Indiana University
August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP