Pilot Study of the Effect of Trastuzumab and GM-CSF on Children With Recurrent Ependymoma

Inclusion Criteria:

• Age ≥ 12 months and < 21 years at the time of study enrollment

• Patients must be diagnosed with relapse of previously histologically confirmed PFEPN

• Magnetic resonance (MR) imaging of the brain (performed within 14 days ofenrollment) must demonstrate no evidence of diffuse leptomeningeal spread beyond theprimary relapse site in posterior fossa and no obstruction of cerebrospinal fluidflow (CSF).

• MR imaging of the total spine (performed within 14 days of enrollment) demonstratesno evidence of spinal metastatic disease.

• Patients must have clinical indication for standard of care surgical resection ofrelapsed PFEPN tumor for enrollment in Stratum 1

• Patients must meet one of the following performance scores:

• Eastern Cooperative Oncology Group (ECOG) performance status scores of 0, 1, or 2;

• Karnofsky score of ≥ 50 for patients > 16 years of age; or

• Lansky score of ≥ 50 for patients ≤ 16 years of age.

• Informed Consent: All patients and/or their parents or legally authorizedrepresentatives must sign a written informed consent. Assent, when appropriate, willbe obtained according to institutional guidelines.

• Organ Function Requirements:

• Adequate Renal Function defined as:

1. Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥70ml/min/1.73 m2 or 2) A serum creatinine based on age/gender as follows:Maximum Serum Creatinine (mg/dL) Age: Male Female 1 month to < 6 months 0.4 0.4 6 months to < 1 year 0.5 0.5 1 to < 2 years 0.6 0.6 2 to < 6 years 0.8 0.8 6 to < 10 years 1 1 10 to < 13years 1.2 1.2 13 to < 16 years 1.5 1.4 ≥ 16 years 1.7 1.4

• Adequate Liver Function defined as:

1. Total bilirubin ≤1.5 x upper limit of normal (ULN) for age, and
2. Serum glutamic oxaloacetic transaminase (SGOT) (AST) or serum glutamatepyruvate transaminase (SGPT) (ALT) < 3 x upper limit of normal (ULN) forage

• Adequate Bone Marrow Function defined as:

1. Peripheral absolute neutrophil count (ANC) ≥1,000/µL
2. Platelet count ≥100,000/µL (transfusion independent)

• Adequate Cardiac Function defined as:

1. Shortening fraction > 28% by echocardiogram or
2. Ejection fraction > 50% by echocardiogram or radionuclide study

Exclusion Criteria:

• Patients with a diagnosis of:

• spinal cord ependymoma,

• myxopapillary ependymoma,

• subependymoma,

• ependymoblastoma,

• supratentorial ependymoma, or

• mixed glioma are NOT eligible for either Stratum.

• Patients with evidence of nodular metastatic spinal disease by MRI are NOT eligiblefor Stratum 1 but may be eligible for STRATUM 2 if CSF flow is not obstructed basedon appropriate imaging studies, and the patient is deemed safe for lumbar punctureby the medical team.

• Patients with clinical contraindications against lumbar puncture are NOT eligiblefor either Stratum.

• Prior Therapy:

• Radiation therapy: At least 28 days must have elapsed (at time of startingprotocol therapy) since completion of focal radiation therapy for currentrecurrence for Stratum 2; Patients who have already undergone radiation therapyfor current recurrence are NOT eligible for Stratum 1.

• Myelosuppressive chemotherapy: At least 21 days must have elapsed after thelast dose of myelosuppressive chemotherapy; Patients who have been treated withchemotherapy at time of recurrence are NOT eligible for either Stratum.

• Monoclonal antibodies: At least three (3) half-lives of the antibody must haveelapsed since the last dose of a monoclonal antibody (see Appendix I for listof half-lives)

• Surgical resection: Must have fully healed from any surgical procedure to besafe for lumbar puncture according to treating neurosurgeon and at least 14days should have elapsed since the surgical procedure.

• Patients who in the opinion of the investigator may not be able to comply with thesafety monitoring requirements of the study are NOT eligible for either Stratum.

• Concomitant Medications

• Corticosteroids: Patients receiving systemic corticosteroids are NOT eligiblefor either Stratum.

• Investigational Drugs: Patients who are currently receiving anotherinvestigational drug are NOT eligible for either Stratum.

• Anti-cancer Agents: Patients who are currently receiving other anti-canceragents are NOT eligible for either Stratum.

• Pregnancy, Breast-Feeding, and Contraception

1. Pregnant or breast-feeding women are NOT eligible. Pregnancy tests must beobtained in females who are post-menarchal.

2. Women of childbearing potential and male participants with partners ofchildbearing potential must agree to:

• use a "highly effective," non-hormonal form of contraception (includingabstinence), or

• two "effective" forms of non-hormonal contraception by the patient and/orpartner, and

• Contraception must continue for the duration of study treatment and for atleast seven (7) months after the last dose of study treatment.

• Patients who have an uncontrolled serious infection are NOT eligible for eitherStratum.

• Patients who have previously received solid organ transplantation are NOT eligiblefor either Stratum.

• Patients who have a history of:

• significant cardiac disease,

• cardiac disease risk factors, or

• uncontrolled arrhythmias are NOT eligible for either Stratum.