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

NCT03109301 | Withdrawn Phase 2 FDA Drug

• 2 other identifiers: 17008417-C-0084
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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. After finishing treatment, participants will be watched for side effects for 30 days.

Conditions

Neoplasms, Nerve Tissue; Neurofibromatosis 1; Heredodegenerative Disorders, Nervous System; Peripheral Nervous System Diseases

Keywords

Mesenchymal Neoplasm; Neurofibromatosis 1; Plexiform Neurofibromas

Outcome Measures

Primary Outcomes (1)

• Efficacy

  Estimate the response rate (radiologic response RECIST v1.1) of selumetinib in children and adults with NF1- mutated measurable gastrointestinal stromal tumor (GIST).

  End of treatment

Study Arms (2)

Arm 1

EXPERIMENTAL

Patients \> 18 years of age

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

Arm 2

EXPERIMENTAL

Patients \< 18 years of age

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

Interventions

Selumetinib (AZD6244 hyd sulfate) 50mg/dose DRUG

Selumetinib will be administered at a starting dose of 50 mg/dose orally in patients 18 years or older; drug will be given twice daily continuously in the absence of toxicity or disease progression, using 28-day cycles.

Arm 1

Selumetinib (AZD6244 hyd sulfate) 25mg/m2 DRUG

Selumetinib will be administered at a starting dose of 25 mg/m2/dose in children \< 18 years of age; drug will be given twice daily continuously in the absence of toxicity or disease progression, using 28-day cycles.

Arm 2

Eligibility Criteria

• Age: 3 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may not qualify if:

• Patients with evidence of another malignancy or benign tumor requiring chemotherapy or radiation therapy are excluded; however, those patients with a plexiform neurofibroma requiring treatment will be eligible as selumetinib has documented activity in plexiform neurofibromas.
• Patients with a diagnosis of NF1 and GIST who do not meet other eligibility criteria may enroll on the NF1 Natural History Study, and will be followed on this study. Should they require therapy for GIST based on evidence of progression, they may then enroll on study.
• Patients who are receiving any other investigational agents.
• Prior therapy with selumetinib or another specific MEK inhibitor is not permitted.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib or other agents used in study.
• Previous MEK, RAS, or RAF inhibitor use.
• Patients who anticipate the need for surgical intervention within the first three cycles (3 months), as surgical intervention during the period of DLT evaluation may affect analysis of adherence and/or make the subject inevaluable.
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Patients with the following cardiac conditions are excluded:
• Uncontrolled hypertension (Adults: blood pressure \[BP\] of greater than or equal to 150/95 despite medical support/management. Participants 18 years of age and younger should have a blood pressure less than or equal to 95th percentile for age, height and gender. Preexisting hypertension in adults should be controlled (either with pharmacological or nonpharmacological methods) at the time of enrollment.)
• Acute coronary syndrome within 6 months prior to starting treatment
• Uncontrolled angina - Canadian Cardiovascular Society grade II-IV despite medical support/management
• Heart failure NYHA Class II or above
• Prior or current cardiomyopathy including but not limited to the following: Known hypertrophic cardiomyopathy
• Known arrhythmogenic right ventricular cardiomyopathy

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

MeSH Terms

Conditions

Neoplasms, Nerve Tissue; Neurofibromatosis 1; Heredodegenerative Disorders, Nervous System; Peripheral Nervous System Diseases; Neurofibroma, Plexiform

Interventions

AZD 6244

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Peripheral Nervous System Neoplasms; Nervous System Neoplasms

Study Officials

• Brigitte C Widemann, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2017
• First Posted: April 12, 2017
• Study Start: April 7, 2017
• Primary Completion: March 27, 2019
• Study Completion: March 27, 2019
• Last Updated: April 5, 2019

Record last verified: 2019-03