Panitumumab and Irinotecan for Malignant Gliomas

Inclusion Criteria:

• Patients must have histologically confirmed diagnosis of primary malignant glioma (glioblastoma multiforme or gliosarcoma). Patients with recurrent disease whose diagnostic pathology confirmed grade IV malignant glioma (glioblastoma multiforme or gliosarcoma) will not need re-biopsy.
• Age ≥ 18 years.
• Evidence of measurable recurrent or residual primary central nervous system (CNS) neoplasm on contrast-enhanced MRI
• An interval of at least 4 weeks between prior surgical resection, or major surgery requiring general anesthesia or 1 week between prior biopsy or minor surgical procedures and study enrollment. The subjects must have recovered from all surgery related toxicities.
• An interval of at least 12 weeks between prior radiotherapy or 4 weeks from prior monthly chemotherapy, or 7 days from daily chemotherapy.
• The lab values following the prior chemotherapy must return to the baseline prior to study enrollment.
• Karnofsky ≥ 70%.
• Hematocrit ≥ 29%, absolute neutrophil count (ANC) ≥ 1,500 cells/μl, platelets ≥ 125,000 cells/μl.
• Serum creatinine ≤ 1.5 mg/dl, serum magnesium, potassium, calcium, chloride, and sodium ≥ the lower limit of normal, serum glutamic-oxaloacetic transaminase (SGOT) and bilirubin ≤ 1.5 times upper limit of normal.
• Signed informed consent approved by the Institutional Review Board prior to patient entry.
• If sexually active, patients will take contraceptive measures for the duration of the treatments, and for 6 months afterwards.

Exclusion Criteria:

• Pregnancy or breast feeding
• Co-medication that may interfere with study results; e.g. immuno¬suppressive agents other than corticosteroids.
• Active infection requiring intravenous antibiotics.
• uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) homozygous for the 7/7 genotype.
• Pre-existing diarrhea greater than Grade 1.

Panitumumab-Specific Concerns:

[Subjects meeting any of the following criteria are ineligible for study entry]

• Prior anti-epidermal growth factor receptor (EGFr) antibody therapy or treatment with small molecule EGFr inhibitors
• Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrollment.
• History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan.
• History of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with the study participation or investigational product(s) administration or may interfere with the interpretation of the results.
• Subject unwilling or unable to comply with study requirements
• Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment.
• Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment.
• Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus, acute or chronic active hepatitis B infection(testing is not required in the absence of clinical suspicion)
• Patients with a history of deep venous thrombosis, pulmonary embolism or on therapeutic anti-coagulation.
• Known allergy or hypersensitivity to any component of the study treatment(s)
• Active infection requiring systemic intravenous treatment of any uncontrolled infections ≤14 days prior to enrollment/randomization.