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
Condition: Colon Cancer; Rectal Cancer
MeSH terms: Rectal Neoplasms; Colonic Neoplasms
Intervention: Cetuximab; Irinotecan; IMC-A12 (cixutumumab)
Intervention description: Cetuximab 500 mg/m² every 14 days until disease progression or participant intolerance; 180 mg/m² every 14 days until disease progression or participant intolerance; IMC-A12 10 mg/kg every 14 days until disease progression or participant intolerance
Intervention MeSH terms: Irinotecan; Cetuximab; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Tumors; Antibodies, Monoclonal; Colorectal Neoplasms; Metastatic K-RAS Wild-Type Carcinoma of the Colon or Rectum

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).
    

Eligibility 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