Phase II Study of Panitumumab in Combination With Irinotecan for Malignant Gliomas
- 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
- 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
- Karnofsky ≥ 70%.
- Hematocrit ≥ 29%, absolute neutrophil count (ANC) ≥ 1,500 cells/μl, platelets ≥
- 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
- If sexually active, patients will take contraceptive measures for the duration of the
treatments, and for 6 months afterwards.
- 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
- Pre-existing diarrhea greater than Grade 1.
[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
- 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.