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 (FC-4)

Lilly

Status and phase: Terminated; Phase 2

Conditions: Colon Cancer; Rectal Cancer

Treatments: Biological: Cetuximab; Biological: IMC-A12 (cixutumumab); Drug: Irinotecan

Study type: Interventional

Funder types: NETWORK; Industry

Identifiers

NCT00845039

I5A-IE-JAED (Other Identifier)

13928

CP13-0708 (Other Identifier)

NSABP FC-4 (Other Identifier)

Details and patient eligibility

About

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).

Full description

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.

Enrollment: 4 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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4 participants in 2 patient groups

Cetuximab + Irinotecan

Active Comparator group

Description:

Participants in Treatment Group 1 will receive intravenous infusions of Cetuximab 500 milligrams per square meter (mg/m²) and Irinotecan 180 mg/m².

Treatment:

Drug: Irinotecan

Biological: Cetuximab

Cetuximab + IMC-A12 + Irinotecan

Experimental group

Description:

Participants in Treatment Group 2 will receive intravenous infusions of Cetuximab 500 mg/m², IMC-A12 10 milligrams/kilogram (mg/kg) and Irinotecan 180 mg/m².

Treatment:

Drug: Irinotecan

Biological: IMC-A12 (cixutumumab)

Biological: Cetuximab