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

J
James Croop, MD, PhD

Primary Investigator

Overview

This phase I trial studies the side effects and the best dose of WEE1 inhibitor MK-1775 when given together with local radiation therapy in treating patients with newly diagnosed diffuse intrinsic pontine gliomas.

Description

The purpose of this study is to estimate the maximum tolerated dose (MTD) or recommended phase 2 dose and schedule of the Wee1 inhibitor AZD1775 (MK-1775) (WEE1 inhibitor MK-1775) administered concurrently with radiation therapy in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG); to define and describe the toxicities of AZD1775 (MK-1775) given concurrently with radiation therapy in children with newly diagnosed DIPG; and to characterize the pharmacokinetics of AZD1775 (MK-1775) in children with newly diagnosed DIPG.

Eligibility

You may be eligible for this study if you meet the following criteria:

  • Conditions:
    glioma
  • Age: Between 1 Years - 21 Years
  • Gender: All

Inclusion Criteria
Patients with newly diagnosed DIPGs, defined as tumors with a pontine epicenter and diffuse involvement of the pons, are eligible without histologic confirmation
Patients with brainstem tumors that do not meet these criteria or are not considered to be typical intrinsic pontine gliomas will only be eligible if the tumors are biopsied and proven to be an anaplastic astrocytoma, glioblastoma, gliosarcoma, or anaplastic mixed glioma; patients with pilocytic astrocytoma, fibrillary astrocytoma, gangliogliomas, or other mixed gliomas without anaplasia are not eligible
Patients with disseminated disease are not eligible, and magnetic resonance imaging (MRI) of spine must be performed if disseminated disease is suspected by the treating physician
Enrollment must be no later than 28 days after the date of radiographic diagnosis or surgery, whichever is the later date
Patients must not have received any prior chemotherapy, radiation therapy, immunotherapy or bone marrow transplant for the treatment of DIPG; prior dexamethasone and/or surgery are allowed
Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlled
Exclusion Criteria
Pregnant or breast-feeding women may not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal
Males or females of reproductive potential may not participate unless they have agreed to use an effective double barrier contraceptive method
Patients receiving corticosteroids are eligible for this trial
Patients who are currently receiving another investigational drug are not eligible
Patients who are currently receiving other anti-cancer agents are not eligible
Patients must not currently be receiving enzyme inducing anticonvulsants
Patients who are currently receiving drugs that are strong or moderate inhibitors and/or inducers of cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) or sensitive CYP3A4 substrates and CYP3A4 substrates with a narrow therapeutic range are not eligible, with the exception of corticosteroids; the use of aprepitant as an antiemetic is prohibited
Caution should be exercised with concomitant administration of AZD1775 (MK-1775) and agents that are sensitive substrates of cytochrome 450 family 2, subfamily C, polypeptide 8 (CYP2C8), 2C9 and 2C19, or substrates of this enzyme with narrow therapeutic ranges, as well as agents that are inhibitors or substrates of P-glycoprotein 1 (P-gp)
Patients must be able to swallow capsules; nasogastric or gastrostomy feeding (G) tube administration is not allowed
Patients who have an uncontrolled infection are not eligible
Patients who have received a prior solid organ transplantation are not eligible
Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible


Additional Information:
Participants will be paid for their participation.

Updated on 20 Nov 2022. Study ID: 1308763990 (PHO-COG-CROOP-ADVL1217)

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