Safety and Efficacy Study of Neratinib and Cetuximab to Treat Patients With Quadruple Wild-Type Metastatic Colorectal Cancer

Inclusion Criteria

• •Patients with resected primary must be active participants of the NSABP Patient Registry and Biospecimen Profiling Repository (MPR-1) study. Patients with intact primary and metastatic KRAS wild-type disease at presentation (treatment naive), must have signed consent for quadruple wild-type central testing for treatment-naive tumor sample submission
• •The Eastern Cooperative Oncology Group (ECOG) performance status must be 0, 1, or 2.
• •Patients must have the ability to swallow oral medication.
• •The tumor tissue must have been determined to be KRAS, NRAS, BRAF, PIK3CA wild-type by central CLIA testing.
• •There must be documentation by PET/CT scan, CT scan, or MRI, that the patient has evidence of measurable metastatic disease per RECIST criteria.
• •Patients must have an accessible metastatic lesion for pretreatment core biopsy procurement.
• •Unless either drug is medically contraindicated, patients must have received oxaliplatin and irinotecan as part of standard chemotherapy regimens. (This includes adjuvant therapy.)
• •Patients must have had at least one prior treatment for metastatic disease with standard chemotherapy and cetuximab in combination or as monotherapy. \[Note: patients who received panitumumab instead of cetuximab are eligible.\]
• •At the time of study entry, blood counts performed within 4 weeks prior to study entry must meet the following criteria: absolute neutrophil count (ANC) must be greater than or equal to 1000/mm3; Platelet count must be greater than or equal to 100,000/mm3; Hemoglobin must be greater than or equal to 9 g/dL
• •The following criteria for evidence of adequate hepatic function performed within 4 weeks prior to study entry must be met: Total bilirubin must be less than or equal to 1.5 x upper limit of normal (ULN); aspartate aminotransferase (AST) and ALT must be less than or equal to 2.5 x ULN for the lab or less than or equal to 5 x ULN if liver metastasis;
• •Serum creatinine performed within 4 weeks prior to study entry must be less than or equal to 1.5 x ULN for the lab.
• •Female patients and male patients with female partners of reproductive potential must agree to use an effective method of contraception during therapy and for at least 6 months after the last dose of study therapy.
• •Patients with acquired immunodeficiency syndrome (AIDS-related illnesses) or known human immunodeficiency virus (HIV) disease must: Have a CD4 count greater than or equal to 200 cells/uL within 30 days prior to beginning study therapy; Be off all antiretroviral therapy (prophylaxis/treatment) greater than 60 days prior to beginning study therapy; Have no evidence of opportunistic infections.
• •Previous serious hypersensitivity reaction to monoclonal antibodies. (Determination of "serious" hypersensitivity reaction is at the investigator's discretion.)
• •Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements.
• •Pregnancy or lactation at the time of study entry.
• •Use of any investigational agent within 4 weeks prior to study entry.