Clinical Trial: WEE1 Inhibitor AZD1775 and Local Radiation Therapy in Treating Younger Patients With Newly Diagnosed Diffuse Intrinsic Pontine Gliomas

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase 1 Study of AZD1775 (MK-1775) Concurrent With Local Radiation Therapy for the Treatment of Newly Diagnosed Children With Diffuse Intrinsic Pontine Gliomas

Brief Summary: This phase I trial studies the side effects and the best dose of WEE1 inhibitor AZD1775 when given together with local radiation therapy in treating patients with newly diagnosed diffuse intrinsic pontine gliomas. WEE1 inhibitor AZD1775 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays, gamma rays, neutrons, protons, or other sources to kill tumor cells and shrink tumors. Giving WEE1 inhibitor AZD1775 with local radiation therapy may work better than local radiation therapy alone in treating diffuse intrinsic pontine gliomas.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) or recommended phase 2 dose and schedule of the WEE1 inhibitor AZD1775 (Wee1 inhibitor AZD1775 [MK-1775]) administered concurrently with radiation therapy in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG).

II. To define and describe the toxicities of WEE1 inhibitor AZD1775 (AZD1775 [MK-1775]) given concurrently with radiation therapy in children with newly diagnosed DIPG.

III. To characterize the pharmacokinetics of AZD1775 (MK-1775) in children with newly diagnosed DIPG.

SECONDARY OBJECTIVES:

I. To preliminarily define the antitumor activity of AZD1775 (MK-1775) within the confines of a phase 1 study, including response rate, progression free survival, and overall survival of treated patients.

II. To assess the biologic activity of AZD1775 (MK-1775) by measuring expression of phosphorylated-cell division cycle 2 G1 to S and G2 to M (p-CDC2) (cyclin-dependent kinase 1 [CDK1]) and phosphorylated-histone H3 (p-HH3) in peripheral blood mononuclear cells (PBMCs) before and after administration of AZD1775 (MK-1775) in children with newly diagnosed DIPG.

III. To assess the biologic activity of AZD1775 (MK-1775) by measuring expression of gamma-H2A histone family, member X (H2AX) in PBMCs, a marker of deoxyribonucleic acid (DNA) double-strand breaks (dsDNA), before and after administration of AZD1775 (MK-1775) in children with newly diagnosed DIPG.

OUTLINE: This is a dose-escalation study of WEE1 inhibitor AZD1775.

  • Incidence and grade of adverse events using the NCI CTCAE version 4.0 [ Time Frame: Up to 4 years ]
  • MTD, defined as the maximum dose at which fewer than one-third of patients experience a dose-limiting toxicity graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 42 days ]


    • Original Primary Outcome:

    • MTD, defined as the maximum dose at which fewer than one-third of patients experience a dose-limiting toxicity (DLT) graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 42 days ]
    • Incidence and grade of adverse events using the NCI CTCAE version 4.0 [ Time Frame: Up to 4 years ]


    Current Secondary Outcome:

    Original Secondary Outcome:

    Information By: National Cancer Institute (NCI)

    Dates:
    Date Received: August 12, 2013
    Date Started: September 2013
    Date Completion:
    Last Updated: May 23, 2017
    Last Verified: May 2017