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

Phase 2

Completed

Interventions: Other: cetuximab in conjunction with external beam radiation therapy, followed by cetuximab and irinotecan

Brief Summary: Standard treatment for patients with diffuse pontine tumors is radiation therapy, but less than 10% of patients are cured. Adding standard chemotherapy has not improved the cure rate.

Standard treatment for high-grade astrocytomas is surgery and radiation. The surgeon removes as much of the tumor as she or he can. Radiation after that tries to kill any cancer cells that are left. Some patients also get chemotherapy. These are anti-cancer drugs. They can be given during or after radiation. Current standard treatments do not cure many patients.

In this study the doctors are adding a new medication called cetuximab to the treatment and will also use a chemotherapy medication (irinotecan) that has been promising for patients treated for recurrent disease.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
pts with high-grade astrocytoma	cetuximab in conjunction with external beam radiation therapy, followed by cetuximab and irinotecan	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.
pts with diffuse pontine tumor	cetuximab in conjunction with external beam radiation therapy, followed by cetuximab and irinotecan	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With High-grade Astrocytoma and Diffuse Pontine Tumors Achieving One Year Progression Free Survival.	1 year
Number of Participants Experiencing Toxicity	2 years	To determine the safety of cetuximab administered weekly in conjunction with involved field external beam radiation therapy for diffuse pontine tumors and high-grade astrocytomas, toxicities will be assessed via the NCI Common Terminology Criteria for Adverse Events (CTCAE, version 3.0)

Secondary Outcome Measures

Name	Time	Method
Event Free Survival	up to 12 months
Number of Participants Who Have Undergone Tumor Analysis	2 years	Participant tumor analysis for potential associations between primary tumor tissue molecular markers and tumor response.
Percentage of Participants With Development of Rash, Either Acneiform and/or Desquamation	2 years	The purpose is to investigate whether the rash associated with cetuximab is secondary to an inflammatory pathway initiated and mediated by the action of cetuximab on host cells.
Number of Participant Tumors Analyzed for Potential Association Between Histology (Grade) With Protein and ELISA Measurements of Those Proteins.	2 years
Time to Progression	2 years
Number of Samples Demonstrating EGFR Copy Number Gain	2 years	Identify gene transcripts for putative cetuximab
Overall Survival	Up to 43 months

Locations (12): Md Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Phoenix Children'S Hospital
🇺🇸
Phoenix, Arizona, United States
University of Colorado Health Sciences Center
🇺🇸
Denver, Colorado, United States
MD Anderson Cancer Center Orlando at Arnold Palmer Hospital for Children
🇺🇸
Orlando, Florida, United States
John Hopkins Medical Center
🇺🇸
Baltimore, Maryland, United States
Children's Healthcare of Atlanta at Egleston
🇺🇸
Atlanta, Georgia, United States
Dana Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Children's Mercy Hospital & Clinics
🇺🇸
Kansas City, Missouri, United States
Alberta Children'S Hospital
🇨🇦
Calgary, Alberta, Canada
University of Florida
🇺🇸
Gainesville, Florida, United States
Seattle Children'S Hospital
🇺🇸
Seattle, Washington, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸
New York, New York, United States