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

Neurofibromatosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01673009
• Other study ID #: 0512-25
• Status: Completed
• Phase: Phase 2
• First received: August 22, 2012
• Last updated: April 5, 2016
• Start date: May 2006
• Est. completion date: August 2012

Study information

• Verified date: April 2016
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: August 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 65 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neurofibroma
• Neurofibroma, Plexiform
• Neurofibromatoses
• Neurofibromatosis

Intervention

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

Locations

Country	Name	City	State
United States	Indiana University	Indianapolis	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Indiana University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline in Tumor Volume at 6 Months	Volumetric measures were performed using MRI scan analysis. Response criteria include greater than 20 percent decrease in tumor volume as responsive. Greater than 20 percent increase in tumor volume as tumor progression. Less then 20 percent increase or decrease in tumor volume is stable disease	baseline to 6 months	No
Secondary	Serum Bioactivity	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)	7 days and 1 month	No