CompletedPhase 1

Study of GDC-0084 in Pediatric Patients With Newly Diagnosed Diffuse Intrinsic Pontine Glioma or Diffuse Midline Gliomas

United States27 participantsStarted 2018-11-19

Plain-language summary

Pediatric high-grade gliomas are highly aggressive and treatment options are limited. The purpose of this first-in-pediatrics study is to examine the safety, tolerability, and pharmacokinetics of GDC-0084 and to estimate its maximum tolerated dose (MTD) when administered to pediatric patients with diffuse intrinsic pontine glioma (DIPG) or other diffuse midline H3 K27M-mutant gliomas after they have received radiation therapy (RT). GDC-0084 is a brain-penetrant inhibitor of a growth-promoting cell signaling pathway that is dysregulated in the majority of diffuse midline glioma tumor cells. This study is also designed to enable a preliminary assessment of the antitumor activity of single-agent GDC-0084, in the hope of enabling rational combination therapy with systemic therapy and/or radiation therapy (RT) in this patient population, which is in desperate need of therapeutic advances. Primary Objectives 1. To estimate the maximum tolerated dose (MTD) and/or the recommended phase 2 dosage (RP2D) of GDC-0084 in pediatric patients with newly diagnosed diffuse midline glioma, including diffuse intrinsic pontine glioma (DIPG) 2. To define and describe the toxicities associated with administering GDC-0084 after radiation therapy (RT) in a pediatric population 3. To characterize the pharmacokinetics of GDC-0084 in a pediatric population Secondary Objectives 1. To estimate the rate and duration of radiographic response in patients with newly diagnosed DIPG or other diffuse midline glioma treated with RT followed by GDC-0084 2. To estimate the progression-free survival (PFS) and overall survival (OS) distributions for patients with newly diagnosed DIPG or other diffuse midline glioma treated with RT followed by GDC-0084

Who can participate

Age range2 Years – 21 Years

SexALL

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Inclusion Criteria: * Age greater than or equal to 2 years and less than 22 years at the time of enrollment * Subjects must have one of the following newly diagnosed tumors: * Non-biopsied typical DIPG, defined as a tumor with a pontine epicenter and diffuse intrinsic involvement of the pons. These subjects are eligible without histologic confirmation. * Biopsied typical DIPG: WHO grade II diffuse astrocytoma (IDH WT or IDH NOS), WHO grade III anaplastic astrocytoma (IDH WT or IDH NOS), WHO grade IV glioblastoma (IDH WT or IDH NOS), or diffuse midline glioma, H3 K27M mutant. Subjects with a typical DIPG who undergo a biopsy may be eligible for the study if the tumor does not harbor the H3 K27M mutation, yet eligibility is restricted to diffuse astrocytoma, anaplastic astrocytoma or glioblastoma, IDH WT or IDH NOS, tumors. * Atypical brainstem glioma: diffuse midline glioma, H3 K27M mutant. * Non-brainstem midline glioma, defined as tumors with an epicenter within midline structures, including the thalamus, spinal cord, and cerebellum: diffuse midline glioma, H3 K27M mutant. * Subjects must have localized, non-metastatic disease; MRI of spine must be performed if disseminated disease is suspected by the treating physician. * Subjects must be able to start radiation therapy no later than 42 days after radiographic diagnosis or surgery, whichever date is later. * Performance score ≥ 50 (Lansky for research subjects aged 16 years or younger and Karnofsky for subjects ol…

What they're measuring

Estimate the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of GDC-0084 after standard-of-care radiation therapy (RT)

Timeframe: 1 month after start of GDC-0084 treatment

Incidence of adverse events at least possibly associated with GDC-0084 after RT by stratum

Timeframe: Up to 2 years after start of GDC-0084 treatment

Pharmacokinetics of GDC-0084 by stratum

Timeframe: GDC-0084 treatment course 1 days 1 and 28

Trial details

NCT IDNCT03696355

SponsorSt. Jude Children's Research Hospital

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2021-04-02

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