Mitogen Activated Protein Kinase Kinase (MEK1/2) Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) in People With Neurofibromatosis Type 1 (NF1) Mutated Gastrointestinal Stromal Tumors (GIST)

Mitogen Activated Protein Kinase Kinase (MEK1/2) Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) in People With Neurofibromatosis Type 1 (NF1) Mutated Gastrointestinal Stromal Tumors (GIST)

NF1 GIST

Withdrawn

2

Start Date 07/26/2017

Age of Trial (yrs) 6.7

First-line, Gleevec-resistant

NF1 GIST

Block related tumor signal paths

Specifically GIST and only GIST

170084 17-C-0084

National Cancer Institute (NCI)

Claudia P Derse-Anthony (240) 760-6102 claudia_derse-anthony@nih.gov

Oral

Background:

Gastrointestinal stromal tumors (GIST) can cause serious medical problems. The only known treatment is surgery. But completely removing a GIST tumor with surgery is often not possible. Researchers want to see if a new drug, selumetinib, can help treat these tumors.

Objective:

To find out if selumetinib shrinks or slows the growth of GIST tumors and to see its side effects.

Eligibility:

People ages 3 and over who have one or more GIST tumors and may have neurofibromatosis type I (also called NF1). Their NF1 GIST has shown some growth or cannot be completely removed with surgery.

Design:

Participants will be screened with heart and eye tests and scans.

Participants will be told what foods and medicines they cannot take during the study. Participants will keep a diary of the medicine they take during the study.

Participants will take selumetinib capsules twice daily on an empty stomach for 28 days in a row. This is 1 cycle.

During the cycles, participants will have study visits. These may include:

Medical history

Physical exam

Blood and urine tests

Heart tests

Scans of their tumors

Eye exam

Positron emission tomography scan. They will be get radioactive glucose an IV line. They will lie quietly in a darkened room for 50-60 minutes then have the scan.

Participants will answer questions about how they are feeling.

Participants can stay in the study until they have bad side effects or their tumor grows.

Criteria:


ELIGIBILITY CRITERIA:
Age: greater than or equal to 3 years of age, BSA greater than or equal to 0.55 m^2, and able to swallow intact capsules.

Diagnosis: must have either a clinical diagnosis of NF1 or a germline NF1 mutation, or in patients without the NF1 syndrome, demonstrate an NF1 mutation in the GIST verified in a CLIA certified laboratory. In patients without the NF1 syndrome, confirmation of the NF1 mutation in the GIST is required for enrollment.

--a) For a clinical diagnosis of NF1 patients must have at least two of the diagnostic criteria for NF1 listed below
Six or more cafe-au-lait macules (greater or equal to 0.5cm in prepubertal subjects or greater than or equal to 1.5 cm in post pubertal subjects)
Freckling in axilla or groin
A neurofibroma or plexiform neurofibroma
Optic glioma
Two or more Lisch nodules
A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)
A first-degree relative with NF1
Patients must have a histologically or cytologically confirmed measurable GIST without PDGFRA or KIT mutations. GIST may be newly diagnosed or recurrent provided that it meets criteria for progressive or metastatic disease. Metastatic disease refers to disease

outside the GI tract, not simply a multifocal primary tumor.

Measurable Disease:
Patients must have measurable GIST as defined by RECIST v 1.1 as at least one lesion not previously irradiated, that can be accurately measured at baseline greater than or equal to 10 mm in the longest diameter (except lymph nodes which must have short axis greater than or equal to 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements.
Progressive disease: GIST has demonstrated progression as defined by RECIST v1.1 within the past 12 months. Patients whose tumors do not meet this criterion, and have a diagnosis of NF1, may enroll on the NF1 Natural History study.

Exclusion Criteria:

Previous MEK, RAS, or RAF inhibitor use.