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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Completed; Phase 2

Conditions: Brain Cancer

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

Study type: Interventional

Funder types: Other

Identifiers

NCT01012609

09-014

Details and patient eligibility

About

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.

Enrollment: 47 patients

Sex: All

Ages: 3 to 21 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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47 participants in 2 patient groups

pts with high-grade astrocytoma

Experimental group

Description:

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.

Treatment:

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

pts with diffuse pontine tumor

Experimental group

Description:

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.

Treatment:

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