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
  Purpose

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


Condition Intervention Phase
Neurofibromatosis
Drug: Gleevec
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Gleevec/Imatinib Mesylate (STI-571, NCS 716051) in Neurofibromatosis (NF1) Patients With Plexiform Neurofibromas

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • Tumor Response [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Tumor response will be evaluated using the RECIST criteria.


Secondary Outcome Measures:
  • 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)


Enrollment: 36
Study Start Date: May 2006
Study Completion Date: August 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.

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/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.

  Eligibility

Ages Eligible for Study:   3 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01673009

Locations
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Indiana University
  More Information

No publications provided by Indiana University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT01673009     History of Changes
Other Study ID Numbers: 0512-25
Study First Received: August 22, 2012
Last Updated: August 24, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Indiana University:
Gleevec

Additional relevant MeSH terms:
Neurofibroma
Neurofibroma, Plexiform
Neurofibromatoses
Neurofibromatosis 1
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Neoplastic Syndromes, Hereditary
Nerve Sheath Neoplasms
Nervous System Diseases
Nervous System Neoplasms
Neurocutaneous Syndromes
Neurodegenerative Diseases
Neuromuscular Diseases
Peripheral Nervous System Diseases
Peripheral Nervous System Neoplasms
Imatinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014