AZD6244 in Children With Low-Grade Gliomas

Low Grade Glioma Clinical Trial

Official title: Phase 1 and Phase II and Re-Treatment Study of AZD6244 for Recurrent or Refractory Pediatric Low Grade Glioma

Status Recruiting

Clinical Trial Summary

Background:

• AZD6244 is an experimental drug designed to prevent tumor growth and shrink existing tumors. It has been studied in adults with cancer, but it has not been studied in children with cancer. Researchers want to see if AZD6244 is a safe and effective treatment for older children and young adults who have gliomas (brain tumors) that have not responded to standard treatments.

Objectives:

• To test the safety and effectiveness of AZD6244 in older children and young adults who have gliomas that have not responded to standard treatments.

Eligibility:

• People between 12 and 21 years of age who have gliomas that have not responded to standard treatments.

Design:

• Participants will be screened with a medical history and physical exam. They will also have blood tests and tumor imaging studies. Those in the study may also have their spinal fluid tested to see whether the cancer has spread to other parts of the nervous system.

• Participants will take AZD6244 as a capsule. It must be swallowed whole on an empty stomach twice a day for 28 days. Those in the study will have up to 13 cycles (4 weeks each) of treatment (1 year).

• Participants will keep a diary to record doses taken and any side effects of the treatment.

• Participants will have frequent blood tests and imaging studies.

Clinical Trial Description

Background

Low Grade Gliomas are among the most common primary CNS neoplasms of childhood.

Debulking surgery and chemotherapy are temporizing strategies that ideally allow tumor stabilization until definitive radiation maybe used. Radiation therapy is associated with long term morbidity.

Patients with high risk features such as hypothalamic location and young age at diagnosis have shown overall survival as low as 60% at 10 years despite multimodal therapies.

AZD6244 (ARRY-142886) is a potent, selective, orally-available, and non-ATP competitive small molecule inhibitor of the mitogen-activated protein (MAP) kinase, MEK-1/2.

Overexpression of growth factors or growth factor receptors involved in the RAS/RAF/MEK/ERK pathway and activating genetic mutations of the signaling proteins may lead to uncontrolled proliferation and tumor formation.

Primary Objectives

To estimate the maximum tolerated dose (MTD) or recommend a Phase II dose of AZD6244 in children with recurrent or refractory low-grade glioma.

To describe the toxicity profile and define the dose limiting toxicity of AZD6244 in children with recurrent or refractory low-grade glioma.COMPLETED April 29, 2013

Phase II

To assess sustained response rate of AZD6244 administered at 25 mg/m (2)/ dose BID, in a single arm Phase II setting in patients in strata based on NF-1 status and presence or absence of BRAF aberrations, specifically BRAF (V600E) mutations and/ or BRAF KIAA1549 fusion identified by IHC and FISH in six (6) patient strata.

Eligibility

Age: Patient must be greater than or equal to 3 and less than or equal to 21 years of age.

Tumor: Patients with refractory low grade glioma (other than pilocytic astrocytoma or optic

pathway glioma) (Stratum 5) must provide consent for BRAF testing. Patients in Stratum 1

or 2 (non-NF-1 non-optic pathway pilocytic astrocytoma) histologically diagnosed may be

required to have pre- treatment tumor tissue available for BRAF analysis. NF-1 patients

with radiographic evidence of low grade glioma, with or without histological diagnosis are

also eligible (Stratum 4). Patients must have bi-dimensionally measureable disease.

Performance status: Karnofsky Performance Scale (if greater than 16 yrs) or Lansky Performance Score (if less than 16 years) greater than or equal to 60%

Must have normal organ and marrow function.

Prior/Concurrent therapy: The patient has received prior therapy other than surgery and must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

Design

Patients will receive AZD6244 25mg/m(2)/ dose orally twice daily approximately 12 hours apart. Four consecutive weeks will constitute one course and subsequent courses will immediately follow, with no break in the administration of the drug.

AZD6244 should be taken on an empty stomach either 1 hour before or 2 hours after meals. AZD6244 capsules should be taken with water only. ;

Study Design

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

Related Conditions & MeSH terms

• Astrocytoma
• Fibriullary Astrocytoma
• Glioma
• Low Grade Glioma
• Optic Glioma
• Pilocytic Astrocytoma

• NCT number: NCT01386450
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Katherine E Warren, M.D.
• Phone: (301) 435-4683
• Email: warrenk@mail.nih.gov
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 2011
• Completion date: November 2018