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

• Status: Terminated
• Trial end date: 2011-02-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Eli Lilly and Company; ImClone LLC
• Collaborator: NSABP Foundation Inc
• Treatments: Antibodies, Monoclonal; Bevacizumab; Camptothecin; Cetuximab; Irinotecan; Oxaliplatin

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