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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)

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ClinicalTrials.gov Identifier: NCT00845039
Recruitment Status : Terminated (Study terminated early 22Feb2010 with only 4 participants due to business reasons.)
First Posted : February 16, 2009
Results First Posted : June 1, 2018
Last Update Posted : July 2, 2018
Sponsor:
Collaborator:
NSABP Foundation Inc
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE February 10, 2009
First Posted Date  ICMJE February 16, 2009
Results First Submitted Date  ICMJE March 17, 2018
Results First Posted Date  ICMJE June 1, 2018
Last Update Posted Date July 2, 2018
Study Start Date  ICMJE May 2009
Actual Primary Completion Date February 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 1, 2018)
Progression-Free Survival (PFS) Rate at 18 Weeks [ Time Frame: Approximately 18 Weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 13, 2009)
Determine the value of adding IMC-A12 to irinotecan + cetuximab in improving PFS at 18 weeks from the date of randomization for patients with metastatic K-RAS wild-type CRC that has progressed on an oxaliplatin/bevacizumab-containing regimen. [ Time Frame: Every 6 weeks for 18 Weeks ]
Change History Complete list of historical versions of study NCT00845039 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 1, 2018)
  • Objective Response Rate (ORR) [Complete Response (CR) + Partial Response (PR)] [ Time Frame: Randomization up to 26.3 months ]
  • Overall Survival (OS) [ Time Frame: Randomization up to 26.3 months ]
  • Progression Free Survival (PFS) Over Entire Duration [ Time Frame: 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) [ Time Frame: Randomization up to 26.3 months ]
  • Toxicity of the Irinotecan + Cetuximab + IMC-A12 Regimen [ Time Frame: Randomization up to 26.3 months ]
  • Post-treatment Serum Levels of IMC-A12 in Participants Receiving IMC-A12 [ Time Frame: 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 [ Time Frame: Baseline, after Cycle 3 (14-day cycle), study discontinuation 30-day follow-up (up to 26.3 months) ]
  • Serum Anti-IMC-A12 Antibody Assessment [ Time Frame: 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 13, 2009)
  • To determine the value of adding IMC-A12 to irinotecan + cetuximab in improving ORR (CR rate plus PR rate). [ Time Frame: 6 weeks ]
  • To determine the value of adding IMC-A12 to irinotecan + cetuximab in improving the median OS. [ Time Frame: 6 weeks ]
  • To determine the value of adding IMC-A12 to irinotecan + cetuximab in improving PFS over the entire duration of the study. [ Time Frame: 6 weeks ]
  • To evaluate the number of patients receiving IMC-A12 + cetuximab + irinotecan who undergo complete resection/ablation of metastases versus the number of patients receiving irinotecan + cetuximab who undergo complete resection/ablation of metastases. [ Time Frame: 6 weeks ]
  • To compare the toxicity of the irinotecan + cetuximab regimen to the irinotecan + cetuximab + IMC-A12 regimen. [ Time Frame: 6 weeks ]
  • To assess the incidence rate of immunogenicity and examine post-treatment serum levels of IMC-A12 in patients receiving IMC-A12. [ Time Frame: 6 weeks ]
Current Other Pre-specified Outcome Measures
 (submitted: May 1, 2018)
The Number of Participants Who Died During 30-Day Follow-Up [ Time Frame: 26.3 months post-randomization up to 30-day post-treatment follow-up ]
Reported are the deaths during the 30-day follow-up period regardless of causality.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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).
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Colon Cancer
  • Rectal Cancer
Intervention  ICMJE
  • 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 Name: Camptosar
  • Biological: IMC-A12 (cixutumumab)
    IMC-A12 10 mg/kg every 14 days until disease progression or participant intolerance
    Other Names:
    • Cixutumumab
    • LY3012217
Study Arms  ICMJE
  • 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.
    Interventions:
    • Biological: Cetuximab
    • Drug: Irinotecan
  • 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.
    Interventions:
    • Biological: Cetuximab
    • Drug: Irinotecan
    • Biological: IMC-A12 (cixutumumab)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: November 23, 2010)
4
Original Estimated Enrollment  ICMJE
 (submitted: February 13, 2009)
100
Actual Study Completion Date  ICMJE February 2011
Actual Primary Completion Date February 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00845039
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eli Lilly and Company
Study Sponsor  ICMJE Eli Lilly and Company
Collaborators  ICMJE NSABP Foundation Inc
Investigators  ICMJE
Study Director: 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
PRS Account Eli Lilly and Company
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP