Pilot Study of Gleevec/Imatinib Mesylate (STI-571, NSC 716051) in Neurofibromatosis (NF1) Patient With Plexiform Neurofibromas

Neurofibromatosis Clinical Trial

— 0908-09  

Official title:

Pilot Study of Gleevec/Imatinib Mesylate (STI-571, NSC 716051) in Neurofibromatosis (NF1) Patient With Plexiform Neurofibromas

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01140360
• Other study ID #: NF/Gleevec DOD Trial
• Secondary ID: 0908-09
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: June 8, 2010
• Last updated: August 4, 2016
• Start date: February 2012
• Est. completion date: December 2016

Study information

• Verified date: August 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

This is a second Pilot Study to determine the efficacy of Gleevec® in neurofibromatosis (NF1) patients with plexiform neurofibromas using new response assessment modalities with the secondary goals of assessing Gleevec toxicity, and characterizing markers of response. The rationale for this study arises from the response of human and murine NF1 cells to Gleevec® in vitro, the response of a NF1 patient treated with Gleevec® for airway compression by a plexiform neurofibroma with a dramatic response not previously seen in NF1 therapy, and the experience in 37 NF1 patients treated with Gleevec® in the initial pilot study. Gleevec will be dosed orally with a starting dose of 100 mg twice daily for patients with a BSA > 1.8 m2 or 55 mg/m2 twice daily for patients with BSA < 1.8 m2. For patients with a BSA > 1.8 m2 the dose will increase by increments of 100 mg bid every two weeks as tolerated up to a maximum dose of 400 mg bid. For patients with a BSA < 1.8 m2 the dose will increase by increments of 55 mg/m2 bid every two weeks as tolerated up to a maximum dose of 220 mg/m2 bid. Treatment will continue for 6 months with an option to continue for 24 months if the patient is deriving a clinical benefit.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: December 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 65 Years

Eligibility

Inclusion criteria

1. Patients > 3 years of age.

2. Diagnosis of neurofibromatosis type 1 (NF1).

3. Presence of clinically significant plexiform neurofibromas (biopsy proven if possible with tissue blocks available); defined as 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).

5. Patients must have a Karnofsky of > 70% or Lansky of > 50% and a life expectancy of > 2 months.

6. 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.

7. Patients must be able to swallow whole pills.

8. 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.

9. 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 or equal to 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.

13. Patients who have or anticipate receiving permanent (or semi-permanent) metallic structures attached to their body. (e.g., braces on teeth, body piercings), which their physicians believe will interfere with the MRI.

Study Design

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

Related Conditions & MeSH terms

• Nerve Sheath Neoplasms
• Neurofibroma
• Neurofibroma, Plexiform
• Neurofibromas
• Neurofibromatoses
• Neurofibromatosis

Intervention

Drug:
• Gleevec
Gleevec will be dosed orally with a starting dose of 100 mg twice daily for patients with a BSA > 1.8 m2 or 55 mg/m2 twice daily for patients with BSA < 1.8 m2. For patients with a BSA > 1.8 m2 the dose will increase by increments of 100 mg bid every two weeks as tolerated up to a maximum dose of 400 mg bid. For patients with a BSA < 1.8 m2 the dose will increase by increments of 55 mg/m2 bid every two weeks as tolerated up to a maximum dose of 220 mg/m2 bid.Treatment will continue for 6 months with an option to continue for 24 months if the patient is deriving a clinical benefit.

Locations

Country	Name	City	State
United States	Riley Hospital for Children	Indianapolis	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Kent Robertson

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pilot Study of Gleevec/Imatinib Mesylate (STI-571, NSC 716051) in Neurofibromatosis (NF1) Patient with Plexiform Neurofibromas	To determine the response rate using standard RECIST criteria.	1 year	No
Secondary	Pilot Study of Gleevec/Imatinib Mesylate (STI-571, NSC 716051) in Neurofibromatosis (NF1) Patient with Plexiform Neurofibromas	To determine the response rate using volumetric analysis of MRI scans, To determine the response rate in metabolic activity by PET imaging To assess quality of life measurements to correlate with the response of plexiform neurofibromas To further assess the safety and tolerability of Gleevec®	1 year	No