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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03109301
• Date of registration: 11/04/2017
• Prospective Registration: No
• Primary sponsor: National Cancer Institute (NCI)
• Public title: Mitogen Activated Protein Kinase Kinase (MEK1/2) Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) in People With Neurofibromatosis Type 1 (NF1) Mutated Gastrointestinal Stromal Tumors (GIST)
• Scientific title: A Phase II Trial of the Mitogen Activated Protein Kinase Kinase (MEK1/2) Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) in Patients With Neurofibromatosis Type 1 (NF1) Mutated Gastrointestinal Stromal Tumors (GIST)
• Date of first enrolment: April 7, 2017
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/show/NCT03109301
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Brigitte C Widemann, M.D.
• Affiliation: National Cancer Institute (NCI)

Key inclusion & exclusion 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. Testing performed
by the Laboratory of Pathology, NCI, unless previously conducted by a CLIA/CAP
external laboratory; analysis will include evaluation of 4 exons of KIT (9, 11, 13,
17) and 3 exons of PDGFRA (12, 14, 18).

- 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.

- Performance Status: ECOG less than or equal to 2 (Patients greater than or equal to 16
years of age must have a Karnofsky performance level of greater than or equal to 70%
(or ECOG less than or equal to 2), and children less than or equal to 16 years old
must have a Lansky performance of greater than or equal to 70%

- Patients must have normal organ and marrow function as defined below:

- absolute neutrophil count greater than or equal to 1,000/mcL

- platelets greater than or equal to 100,000/mcL

- hemoglobin (Hgb) greater than or equal to 9.0 g/dL

- total bilirubin < 1.5(SqrRoot) institutional upper limit of normal

- AST(SGOT)/ALT(SGPT) < 3.0 (SqrRoot) institutional upper limit of normal

- creatinine clearance or radioisotope GFR > 60 mL/min/1.73 m^2 by either
Cockcroft- Gault formula or analysis normal serum creatinine based on age
described below:

- Age (years): less than or equal to 5; Maximum Serum Creatinine (mg/dL): 0.8

- Age (years): 5 or less or equal to 10; Maximum Serum Creatinine (mg/dL): 1.0

- Age (years): 10 or less than or equal to 15; Maximum Serum Creatinine
(mg/dL): 1.2

- Age (years): >15; Maximum Serum Creatinine (mg/dL): 1.5

- Prior Therapy: Patients will be eligible if tumor is metastatic, unresectable,
progressive, or if complete tumor resection is not considered to be feasible without
substantial risk or morbidity.

- Since there is no standard effective chemotherapy for patients with NF1 and GIST,
patients may be treated on this trial without having received prior medical
therapy directed at their GIST. Patients who have had prior GIST-directed surgery
may enroll provided they have measurable disease.

- Since selumetinib is not expected to cause substantial myelosuppression, there
will be no limit to number of prior myelosuppressive regimen for GIST or other
tumor manifestations associated with NF1.

- Patients who have received previous investigational agents or biologic therapy,
such as tipifarnib, pirfenidone, Peg-Intron, sorafenib, imatinib or other
targeted therapies are eligible for enrollment. At least 4 weeks must have
elapsed since receiving medical therapy directed at the PN and patients who
received previous GIST-directed therapy must either demonstrate progression as
defined by RECIST, or be unable to tolerate their previous therapy. Patients who
received effects of all prior therapy to less than or equal to grade 1 before
entering this study.

- Cytotoxic chemotherapy last dose must have been received at least 28 days prior
to enrollment, their last dose of biological therapy, immunomodulatory agents,
vaccines, differentiating agents, used to treat their cancer at least 7 days
prior to enrollment, their last dose of a monoclonal antibody at least 30 days
prior to enrollment, and their last dose of any investigational agent at least 30
days prior

to enrollment.

- Growth factors that support platelet or white cell number or function must not have
been administered within the 7 days prior to enrollment.

- At least 6 weeks must have elapsed prior to enrollment since the patient received any
prior radiation therapy.

- At least 4 weeks must have elapsed since any surgeries, with evidence of good wound
healing.

- The effects of selumetinib on the developing human fetus at the recommended
therapeutic dose are unknown. For this reason, women of child-bearing potential
and men must agree to use adequate contraception (hormonal or barrier method of
birth control; abstinence) prior to study entry, for the duration of study
participation, and for 4 weeks after dosing with selumetinib ceases. Women of
child-bearing potential must have a negative pregnancy test prior to entry.
Should a woman become pregnant or suspect she is pregnant while she or her
partner


Age minimum: 3 Years
Age maximum: 99 Years
Gender: All

Health Condition(s) or Problem(s) studied

Peripheral Nervous System Diseases

Neoplasms, Nerve Tissue

Heredodegenerative Disorders, Nervous System

Neurofibromatosis 1

Intervention(s)

Drug: Selumetinib (AZD6244 hyd sulfate) 25mg/m2

Drug: Selumetinib (AZD6244 hyd sulfate) 50mg/dose

Primary Outcome(s)

Efficacy [Time Frame: End of treatment]

Secondary ID(s)

170084

17-C-0084

Source(s) of Monetary Support

Please refer to primary and secondary sponsors