Study of the IDO Pathway Inhibitor, Indoximod, and Temozolomide for Pediatric Patients With Progressive Primary Malignant Brain Tumors
Glioblastoma Multiforme, Glioma, Gliosarcoma
About this trial
This is an interventional treatment trial for Glioblastoma Multiforme focused on measuring glioblastoma multiforme, glioma, gliosarcoma, malignant brain tumor, ependymoma, medulloblastoma
Eligibility Criteria
Eligibility Criteria
- Age: 3-21 years.
- Group 1 or Group 3: histologically proven initial diagnosis of primary malignant brain tumor, with no known curative treatment options.
- Group 2: histologically proven initial diagnosis of high-grade glioma (WHO grade III and IV), ependymoma, medulloblastoma, or other primary central nervous system tumor.
- Group 3b: Patients with a radiographic diagnosis or histologically proven diagnosis of diffuse intrinsic pontine glioma (DIPG).
- MRI confirmation of tumor progression or regrowth.
- Patients must be able to swallow whole capsules.
- Patients with metastatic disease are eligible for enrollment.
- Lansky or Karnofsky performance status score must be > 50%.
- Seizure disorders must be well controlled on antiepileptic medication.
- DIPG patients enrolled to Group 3b must not have been previously treated with radiation or any medical therapy.
- Patients previously treated with temozolomide, cyclophosphamide, and/or etoposide are eligible for enrollment.
Exclusion Criteria
- Prior invasive malignancy, other than the primary central nervous system tumor, unless the patient has been disease free and off therapy for that disease for a minimum of 3 years
- Patients with baseline QTc interval of more than 470 msec at study entry, and patients with congenital long QTc syndrome.
- Active autoimmune disease
Sites / Locations
- Children's Hospital Colorado
- Arnold Palmer Hospital for Children
- Children's Heathcare of Atlanta
- Augusta University
- Children's Hospitals and Clinics of Minnesota
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Experimental
Experimental
Experimental
Experimental
Experimental
Group 1 (CLOSED)
Group 2 (CLOSED)
Group 3 (CLOSED)
Group 3b
Group 4
Core Regimen: Dose-escalation of indoximod, in combination with temozolomide, for pediatric patients with progressive brain tumors. Indoximod will be administered in escalating doses. Initial dosing will be 12.8 mg/kg/dose BID with escalation planned to 22.4 mg/kg/dose BID. Temozolomide to be given at 200 mg/m^2 x 5 days
Expansion cohorts: Indoximod therapy at the pediatric recommended phase 2 dose (RP2D) determined by Group 1, in combination with temozolomide. Indoximod will be administered at the RP2D of 19.2 mg/kg/dose BID. Temozolomide to be given at 200 mg/m^2 x 5 days
Dose-escalation of indoximod, in combination with up-front conformal radiation therapy, for pediatric patients with progressive brain tumors. Indoximod will be administered in escalating doses. Initial dosing will be 12.8 mg/kg/dose BID with escalation planned to 22.4 mg/kg/dose BID. Temozolomide to be given at 200 mg/m^2 x 5 days
Indoximod, in combination with up-front conformal radiation therapy, for pediatric patients with newly diagnosed treatment-naive diffuse intrinsic pontine glioma (DIPG). Indoximod will be administered at the RP2D of 19.2 mg/kg/dose BID. Temozolomide to be given at 200 mg/m^2 x 5 days
Continued access to indoximod in combination with low-dose oral cyclophosphamide and etoposide for patients with progressive disease after treatment with indoximod plus temozolomide. Indoximod will be administered at 32 mg/kg/dose divided twice daily. Cyclophosphamide to be given at 2.5 mg/kg/dose daily Etoposide to be given at 50 mg/m2/dose daily