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

NCT00845039 | Terminated Phase 2 Results

• 4 other identifiers: 13928CP13-0708I5A-IE-JAEDNSABP FC-4
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 3

Brief 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).

Conditions

Colon Cancer; Rectal Cancer

Keywords

Tumors; Antibodies, Monoclonal; Colorectal Neoplasms; Metastatic K-RAS Wild-Type Carcinoma of the Colon or Rectum

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS) Rate at 18 Weeks

  Approximately 18 Weeks

Secondary Outcomes (8)

• 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

Other Outcomes (1)

• The Number of Participants Who Died During 30-Day Follow-Up

  26.3 months post-randomization up to 30-day post-treatment follow-up

Study Arms (2)

Cetuximab + Irinotecan

ACTIVE COMPARATOR

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; Drug: Irinotecan

Cetuximab + IMC-A12 + Irinotecan

EXPERIMENTAL

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

Interventions

Cetuximab BIOLOGICAL

Cetuximab 500 mg/m² every 14 days until disease progression or participant intolerance

Also known as: Erbitux, LY2939777

Cetuximab + IMC-A12 + Irinotecan; Cetuximab + Irinotecan

Irinotecan DRUG

180 mg/m² every 14 days until disease progression or participant intolerance

Also known as: Camptosar

Cetuximab + IMC-A12 + Irinotecan; Cetuximab + Irinotecan

IMC-A12 (cixutumumab) BIOLOGICAL

IMC-A12 10 mg/kg every 14 days until disease progression or participant intolerance

Also known as: Cixutumumab, LY3012217

Cetuximab + IMC-A12 + Irinotecan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead
• NSABP Foundation Inc: collaborator

Study Sites (3)

ImClone Investigational Site

Vallejo, California, 94589, United States

Location

ImClone Investigational Site

Greenville, North Carolina, 27834, United States

Location

ImClone Investigational Site

Scranton, Pennsylvania, 18510, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms; Neoplasms; Colorectal Neoplasms

Interventions

Cetuximab; Irinotecan; cixutumumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds

Limitations and Caveats

Study terminated early 22Feb2010 with only 4 participants due to business reasons. Data were collected for too few participants to draw statistically meaningful conclusions and included concerns on participant confidentiality.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2009
• First Posted: February 16, 2009
• Study Start: May 1, 2009
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: July 2, 2018
• Results First Posted: June 1, 2018

Record last verified: 2018-06

Locations

US (3)