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
Condition: Brain Cancer
MeSH terms: Astrocytoma; Brain Neoplasms; Brain Stem Neoplasms
Intervention: cetuximab in conjunction with external beam radiation therapy, followed by cetuximab and irinotecan
Intervention description: External beam radiation therapy (5940 cGy in 180 cGy fractions) with weekly cetuximab (250 mg/m2/dose).4-8 weeks rest, 10 cycles of irinotecan (16 mg/m2/day x 5 consecutive days x 2 weeks) with weekly cetuximab (250 mg/m2/dose) at about 21 day intervals. Research biological evaluations will be performed in consenting patients as an optional portion of the study. Cetuximab is to be given every 7 days (+/- 2 days). Cetuximab does not need to be given on Day 1 of each week.
Intervention MeSH terms: Irinotecan; Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 47.0
Sex: All
Minimum age: 3 Years
Maximum age: 21 Years
Healthy volunteers: No
Keywords: high-grade astrocytomas; newly diagnosed diffuse pontine tumors; External beam radiation therapy; cetuximab; irinotecan; POETIC

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.
    

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.