A Phase 2 Study of Panitumumab in Patients With Cetuximab-refractory Metastatic Colorectal Cancer

A Phase 2 Study of Panitumumab in Patients With Cetuximab-refractory Metastatic Colorectal Cancer

The purpose of this study is to assess if panitumumab is active enough to warrant comparative studies in patients with metastatic colorectal cancer that has progressed after treatment with cetuximab.

The study was amended with modification of inclusion criteria (from wild-type tumor KRAS gene to wild-type RAS gene, including KRAS and NRAS exons 2, 3 and 4)

RAS mutational status of tumors of patients enrolled before amendment 1 approval will be centrally revised. Patients whose tumors will result RAS mutated at the biomarkers central revision, will be replaced. Therefore, the overall sample size at both the stages may be higher than the one initially planned.

Inclusion Criteria:

• Pathologic diagnosis of metastatic colorectal adenocarcinoma
• a wild-type RAS tumor (mutational status has to be determined by an experienced laboratory using validated test methods for detection of KRAS exons 2, 3, and 4, and NRAS exons 2, 3, and 4
• Failure from previous treatment with fluoropyrimidine, oxaliplatin and irinotecan. Patients may or may not have been treated with bevacizumab.
• Documented disease progression following a treatment with cetuximab in patients who showed either an objective response after 8 weeks or stable disease after 16 weeks of cetuximab treatment.
• Age at least 18 years
• ECOG Performance Status 0-2
• Neutrophils at least 1,500 mm3, platelets at least 100,000 mm3, and hemoglobin at least 9 g/dL
• Bilirubin level less than 1.5 times ULN
• AST (SGOT) and ALT (SGPT) not greater than 2.5 times ULN (or 5 times ULN in presence of liver metastasis)
• Serum creatinine less than 1.5 times ULN
• Effective contraception, if the risk of conception exists
• Life expectancy at least 3 months
• Written informed consent

Exclusion Criteria:

• Symptomatic brain metastasis
• Interstitial pneumonitis or pulmonary fibrosis
• Any other malignancies within 5 years (except for adequately treated carcinoma in situ of the cervix or non melanoma skin cancer)
• Chemotherapy, radiotherapy or immunotherapy within the past 4 weeks
• Any unstable systemic disease (including active infections, any significant hepatic, renal or metabolic disease), metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of study drugs or render the patient at high risk from treatment complications
• Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment