External Beam Radiation Therapy and Cetuximab Followed by Irinotecan and Cetuximab for Children and Young Adults With Newly Diagnosed Diffuse Pontine Tumors and High-Grade Astrocytomas
Brain Cancer
About this trial
This is an interventional treatment trial for Brain Cancer focused on measuring high-grade astrocytomas, newly diagnosed diffuse pontine tumors, External beam radiation therapy, cetuximab, irinotecan, POETIC
Eligibility Criteria
Inclusion Criteria:
- Patients must have either (1) histologic proof of a high-grade astrocytoma reviewed by a POETIC institutional pathologist or (2) a radiological diagnosis via MRI scan of a typical diffuse pontine tumor made by a POETIC institutional neuroradiologist. Patients with a radiological diagnosis via MRI scan of a typical diffuse pontine tumor will be enrolled on the diffuse pontine tumor arm of the study regardless of histology in cases that are biopsied. Note: For collaborating non-POETIC institutions, the reviews may be done by an institutional pathologist/neuroradiologist.
- Patients must begin study prescribed therapy within 42 days of neurosurgical resection or biopsy of the tumor (high-grade astrocytoma patients) or radiological diagnosis (diffuse pontine tumor patients).
- Age ≥ 3-years and < 22-years-old.
- Brain MRI (and any other studies done according to clinical indications) must not show any definitive evidence of leptomeningeal or extra-neural metastases.
- ANC ≥ 1000/μL and platelet count ≥ 100,000/μL
- Patients must have adequate organ function as defined by:
- Hepatic: total bilirubin < 1.5 mg/dl, AST ≤ 2.5 x the upper limit of normal.
- Renal: serum creatinine ≤ 1.5 x the upper limit of normal for age, or calculated creatinine clearance or nuclear GFR ≥ 70 ml/min/1.73 m2.
- The patient, or for minors, a parent or legal guardian, must give informed written consent indicating they are aware of the investigational nature of this study.
Exclusion Criteria:
- Evidence of leptomeningeal or extra-neural metastatic disease.
- Prior radiation therapy or chemotherapy
- Pregnancy, mothers unwilling to refrain from breast-feeding, and sexually mature patients unwilling to practice an effective form of birth control.
- Other significant concomitant medical illnesses that would compromise the patient's ability to receive all prescribed study therapy.
- Prior therapy which specifically and directly targets the EGFR pathway.
- Prior severe infusion reaction to a monoclonal antibody.
- Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction.
- Patients with known Gilbert's Syndrome.
Sites / Locations
- Phoenix Children'S Hospital
- University of Colorado Health Sciences Center
- University of Florida
- MD Anderson Cancer Center Orlando at Arnold Palmer Hospital for Children
- Children's Healthcare of Atlanta at Egleston
- John Hopkins Medical Center
- Dana Farber Cancer Institute
- Children's Mercy Hospital & Clinics
- Memorial Sloan-Kettering Cancer Center
- Md Anderson Cancer Center
- Seattle Children'S Hospital
- Alberta Children'S Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
pts with high-grade astrocytoma
pts with diffuse pontine tumor
This is a 2-group parallel (high-grade astrocytoma, diffuse pontine tumor), single stage study investigating cetuximab in conjunction with external beam radiation therapy, followed by cetuximab and irinotecan in pediatric and young adult patients. Optional exploratory components of the study include (1) correlation of tumor molecular markers with outcome, (2) CSF proteomics, and (3) assay of serum cytokine levels in patients who develop a cetuximab-associated rash.
This is a 2-group parallel (high-grade astrocytoma, diffuse pontine tumor), single stage study investigating cetuximab in conjunction with external beam radiation therapy, followed by cetuximab and irinotecan in pediatric and young adult patients. Optional exploratory components of the study include (1) correlation of tumor molecular markers with outcome, (2) CSF proteomics, and (3) assay of serum cytokine levels in patients who develop a cetuximab-associated rash.