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)

A Randomized Phase II Clinical Trial Investigating Irinotecan Plus Cetuximab With or Without Anti-Insulin-Like Growth Factor-I Receptor Monoclonal Antibody (IMC-A12) for the Treatment of Patients With Metastatic K-Ras Wild Type Carcinoma of the Colon or Rectum That Has Progressed on Oxaliplatin and Bevacizumab Given as First-Line Therapy

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).

Study Overview

• Status: Terminated
• Conditions: Rectal Cancer; Colon Cancer
• Intervention / Treatment: Biological: Cetuximab; Drug: Irinotecan; Biological: IMC-A12 (cixutumumab)

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Vallejo, California, United States, 94589
      • ImClone Investigational Site
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • ImClone Investigational Site
  • Pennsylvania
    • Scranton, Pennsylvania, United States, 18510
      • ImClone Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cetuximab + Irinotecan; Participants in Treatment Group 1 will receive intravenous infusions of Cetuximab 500 milligrams per square meter (mg/m²) and Irinotecan 180 mg/m².	Biological: Cetuximab; Cetuximab 500 mg/m² every 14 days until disease progression or participant intolerance; Other Names: Erbitux; LY2939777; Drug: Irinotecan; 180 mg/m² every 14 days until disease progression or participant intolerance; Other Names: Camptosar
Experimental: Cetuximab + IMC-A12 + Irinotecan; 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.	Biological: Cetuximab; Cetuximab 500 mg/m² every 14 days until disease progression or participant intolerance; Other Names: Erbitux; LY2939777; Drug: Irinotecan; 180 mg/m² every 14 days until disease progression or participant intolerance; Other Names: Camptosar; Biological: IMC-A12 (cixutumumab); IMC-A12 10 mg/kg every 14 days until disease progression or participant intolerance; Other Names: Cixutumumab; LY3012217

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-Free Survival (PFS) Rate at 18 Weeks	Approximately 18 Weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate (ORR) [Complete Response (CR) + Partial Response (PR)]	Randomization up to 26.3 months
Overall Survival (OS)	Randomization up to 26.3 months
Progression Free Survival (PFS) Over Entire Duration	Randomization up to 26.3 months
The Number of Participants Who Had a Complete Resection/Ablation of Metastases With no Evidence of Disease Remaining (Resection Rate)	Randomization up to 26.3 months
Toxicity of the Irinotecan + Cetuximab + IMC-A12 Regimen	Randomization up to 26.3 months
Post-treatment Serum Levels of IMC-A12 in Participants Receiving IMC-A12	Prior to infusion at Cycles 1, 4, 7 (2-week cycles), and 4 to 6 weeks following discontinuation of treatment IMC-A12 up to 77 weeks
Change in Behavioral and Health Outcomes [BAHO] Quality of Life (QoL) Questionnaire	Baseline, after Cycle 3 (14-day cycle), study discontinuation 30-day follow-up (up to 26.3 months)
Serum Anti-IMC-A12 Antibody Assessment	Prior to infusion at Cycles 1, 4, 7 (2-week cycles), and 4 to 6 weeks following discontinuation of treatment IMC-A12 up to 77 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Participants Who Died During 30-Day Follow-Up	Reported are the deaths during the 30-day follow-up period regardless of causality.	26.3 months post-randomization up to 30-day post-treatment follow-up

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: NSABP Foundation Inc

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: February 10, 2009
• First Submitted That Met QC Criteria: February 13, 2009
• First Posted (Estimate): February 16, 2009

Study Record Updates

• Last Update Posted (Actual): July 2, 2018
• Last Update Submitted That Met QC Criteria: June 1, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Tumors; Antibodies, Monoclonal; Colorectal Neoplasms; Metastatic K-RAS Wild-Type Carcinoma of the Colon or Rectum
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Colonic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Topoisomerase I Inhibitors; Irinotecan; Antibodies, Monoclonal; Cetuximab
• Other Study ID Numbers: 13928; CP13-0708 (Other Identifier: ImClone, LLC); I5A-IE-JAED (Other Identifier: Eli Lilly and Company); NSABP FC-4 (Other Identifier: The National Surgical Adjuvant Breast and Bowel Project)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No