WEE1 Inhibitor AZD1775 and Local Radiation Therapy in Treating Children With Newly Diagnosed Diffuse Intrinsic Pontine Gliomas

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

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 children with newly diagnosed diffuse intrinsic pontine gliomas. WEE1 inhibitor AZD1775 may stop the growth of tumour 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 tumour cells and shrink tumours. Giving WEE1 inhibitor AZD1775 with local radiation therapy may work better than local radiation therapy alone in treating diffuse intrinsic pontine gliomas.

Trial Description

Primary Outcome:

  • Incidence and grade of adverse events using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
  • Maximum tolerated dose (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
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 when given concurrently with radiation therapy. SECONDARY OBJECTIVES:
I. To preliminarily define the antitumour 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. Patients undergo radiation therapy 5 days a week for 6 weeks (up to 30 fractions). Patients also receive WEE1 inhibitor AZD1775 orally (PO) on days 1-5 of weeks 1, 3, and 5; days 1-5 of weeks 1, 3, and 5 AND days 1, 3, and 5 of weeks 2, 4, and 6; OR days 1-5 of weeks 1-6 depending on dose level assignment. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, every 2 months for 6 months, and then every 3 months thereafter.

View this trial on ClinicalTrials.gov

Interested in this trial?

Print this page and take it to your doctor to discuss your eligibilty and treatment options. Only your doctor can refer you to a clinical trial.

Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society