a study of irinotecan and cetuximab with or without imc-a12 for treatment of participants with colon or rectum cancer who got worse after their first treatment with oxaliplatin and bevacizumab

Conditions: Colon Cancer; Rectal Cancer

Summary: the purpose of this study is to determine the value of adding imc-a12 to irinotecan and cetuximab in participants with metastatic colorectal cancer (crc).

the purpose of this study is to determine the value of adding imc-a12 to irinotecan + cetuximab in improving progression-free survival (pfs) at 18 weeks from the date of randomization for participants with metastatic kirsten rat sarcoma (k-ras) wild-type crc that has progressed on an oxaliplatin/bevacizumab-containing regimen.

Eligibility criteria:
inclusion criteria: * must consent to be in the study and must have signed and dated institutional review board (irb)-approved consent forms conforming to federal and institutional guidelines for the pre-entry tumor sample submission for central k-ras testing and for the study treatment * must have an eastern cooperative oncology group (ecog) performance status of 0, 1, or 2 * must have metastatic crc * the crc tumor or metastatic tumor must be v-ki-ras2 kirsten rat sarcoma viral oncogene homolog gene (k-ras) wild-type as determined by central testing * must be documented disease progression during first-line therapy containing both oxaliplatin and bevacizumab * most recent treatment regimen must have ended ≥21 days prior to randomization, and clinically significant side effects associated with previous therapy must have resolved to ≤grade 1 with the exception of neuropathy which must have resolved to ≤grade 2 * imaging of the chest, abdomen and pelvis with computed tomography (ct) scan or magnetic resonance imaging (mri) must be performed within 3 weeks prior to randomization * must have measurable disease, defined as at least 1 lesion outside a previous radiation therapy (rt) field that can be accurately measured in at least 1 dimension as ≥20 millimeters (mm) with conventional techniques or as ≥10mm with 5mm cuts using a spiral ct scan * evidence of adequate bone marrow function: absolute neutrophil (anc) ≥1200 cubed millimeters (mm³), hemoglobin ≥9 grams per deciliter (g/dl), platelets ≥100,000 mm³ * evidence of adequate hepatic function. if no liver metastases: aspartate aminotransferase (ast) ≤2.5 times (x) upper limit of normal (uln), total bilirubin ≤1.5 x uln for the lab. in the presence of liver metastases: ast ≤5.0 x uln, total bilirubin ≤1.5 x uln for the lab * serum creatinine must be ≤1.5 x uln for the lab * must have a fasting blood glucose \<126 milligrams/deciliter (mg/dl). fasting is defined as no caloric intake for at least 8 hours exclusion criteria: * life expectancy less than 12 weeks * diagnosis of anal or small bowel carcinoma * tumor that is considered by the surgeon to be amenable to complete resection * previous rt to \>25% of bone marrow * rt to sites of measurable disease chosen as target lesions * radiological evidence and/or clinical signs or symptoms of central nervous system (cns) metastases * any of the following conditions and events: uncontrolled hypertension, defined as systolic blood pressure (bp) \>150 millimeters of mercury (mmhg) or diastolic bp \>100 mmhg with or without antihypertensive medication (participants with hypertension that is well-controlled on medication are eligible); unstable angina within 6 months before randomization; new york heart association (nyha) class iii or iv cardiac disease; myocardial infarction (mi) within 6 months before randomization; symptomatic arrhythmia; cns cerebrovascular ischemia \[transient ischemic attack (tia) or stroke\] within 6 months before randomization * other malignancies unless the participant is considered to be disease-free and has completed therapy for the malignancy ≥12 months prior to randomization. participants with the following cancers are eligible if diagnosed and treated within the past 12 months: carcinoma in situ of the cervix, colon carcinoma in situ, melanoma in situ, and basal cell and squamous cell carcinoma of the skin * serious or non-healing wound, skin ulcers, or bone fracture * any significant bleeding unless the source of bleeding has been resected * history of bleeding diathesis or coagulopathy (participants on stable anticoagulant therapy are eligible) * any evidence of active infection * active inflammatory bowel disease * grade 3 or 4 diabetes mellitus as defined by national cancer institute's (nci's) common terminology criteria for adverse events (ctcae) v 3.0 pancreatic endocrine: glucose intolerance (participants with diabetes controlled with diet and/or oral medications are eligible) * symptomatic interstitial pneumonitis or definitive evidence of interstitial pneumonitis described on ct scan or chest x-ray in asymptomatic participants * any other serious concomitant medical condition that, in the opinion of the investigator, would compromise the safety of the participant or compromise the participant's ability to participate in the study * previous hypersensitivity reaction to monoclonal antibodies * previous treatment with irinotecan, cetuximab, or any agent specifically targeting insulin-like growth factor (igf) receptors * treatment with an investigational drug within 30 days prior to randomization * pregnancy or lactation at the time of participant entry * psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the participant from meeting the study requirements

Keywords: tumors antibodies, monoclonal colorectal neoplasms metastatic k-ras wild-type carcinoma of the colon or rectum