Pediatric Trial of Indoximod With Chemotherapy and Radiation for Relapsed Brain Tumors or Newly Diagnosed DIPG

Summary

Indoximod was developed to inhibit the IDO (indoleamine 2,3-dioxygenase) enzymatic pathway, which is important in the natural regulation of immune responses. This potent immune suppressive mechanism has been implicated in regulating immune responses in settings as diverse as infection, tissue/organ transplant, autoimmunity, and cancer. By inhibiting the IDO pathway, we hypothesize that indoximod will improve antitumor immune responses and thereby slow the growth of tumors.

The central clinical hypothesis for the GCC1949 study is that inhibiting the pivotal IDO pathway by adding indoximod immunotherapy during chemotherapy and/or radiation is a potent approach for breaking immune tolerance to pediatric tumors that will improve outcomes, relative to standard therapy alone.

This is an NCI-funded (R01 CA229646, MPI: Johnson and Munn) open-label phase 2 trial using indoximod-based combination chemo-radio-immunotherapy for treatment of patients age 3 to 21 years who have progressive brain cancer (glioblastoma, medulloblastoma, or ependymoma), or newly-diagnosed diffuse intrinsic pontine glioma (DIPG). Statistical analysis will stratify patients based on whether their treatment plan includes up-front radiation (or proton) therapy in combination with indoximod. Central review of tissue diagnosis from prior surgery is required, except non-biopsied DIPG. This study will use the "immune-adapted Response Assessment for Neuro-Oncology" (iRANO) criteria for measurement of outcomes. Planned enrollment is up to 140 patients.

Conditions

• Glioblastoma
• Medulloblastoma
• Ependymoma
• Diffuse Intrinsic Pontine Glioma

Interventions

DRUG

Cyclophosphamide

Cyclophosphamide will be taken by mouth once daily, on days 1-21 of each chemo-immunotherapy treatment cycle.

DRUG

Etoposide

Etoposide will be taken by mouth once daily, on days 1-21 of each chemo-immunotherapy treatment cycle.

DRUG

Indoximod

Indoximod will be taken by mouth twice daily during radiation and throughout each chemo-immunotherapy treatment cycle.

RADIATION

Partial Radiation

Palliative low-dose or partial-field radiation plan (low-dose radiation or not all disease sites included).

RADIATION

Full-dose Radiation

Palliative full-dose radiation plan to all known sites of disease (\>50 Gy to brain, \>45 Gy to spine).

DRUG

Temozolomide

Temozolomide will be taken by mouth once daily, on days 1-5 of each chemo-immunotherapy treatment cycle.

DRUG

Lomustine

Lomustine will be taken by mouth once daily, on day 1 of each chemo-immunotherapy treatment cycle.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• Augusta University

  collaborator OTHER

• Emory University

  collaborator OTHER

• Theodore S. Johnson

  lead OTHER

Principal Investigators

• Theodore S Johnson, MD, PhD · Augusta University

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

3 Years

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-10-02

Primary Completion

2026-08-02

Completion

2027-10-02

FDA Drug

Yes

Countries

• United States

Study Locations