Study Using IMC-A12 (Cixutumumab) With or Without Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Failed a Treatment Regimen That Consisted of a Prior Anti-EGFR Therapy
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms; Disease Progression
Intervention: IMC-A12; cetuximab
Intervention description: 10 milligrams/kilogram (mg/kg) intravenous infusion every 2 weeks.; Participants will receive cetuximab 500 milligrams/square meter (mg/m²) intravenous over 2 hours every 2 weeks.
Intervention MeSH terms: Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 65.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic Colorectal Cancer with Disease Progression; Failed prior to Anti-EGFr Therapy

Summary:

      Participants with metastatic Colorectal Cancer (mCRC) who have progressed on a prior
      Anti-epidermal growth factor receptor (EGFR) regimen randomized to receive IMC-A12
      monotherapy or combination therapy with cetuximab to assess response, survival, durations of
      response, safety and tolerability as well as pharmacodynamics of IMC-A12 and cetuximab
    

Eligibility criteria:

        Inclusion Criteria

          -  The participant has histologically or cytologically-confirmed colorectal cancer with
             metastatic disease documented on diagnostic imaging studies

          -  The participant has measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded),
             measuring ≥ 2 centimeter (cm) on conventional measurement techniques or ≥ 1 cm on
             spiral computed tomography (CT) scan

          -  The participant has clinical documentation of disease progression during treatment or
             within 6 weeks after receiving the last dose of a therapeutic regimen for metastatic
             disease containing an anti-EGFR-component (cetuximab or panitumumab). Toxicity or
             planned treatment break will not be regarded as adequate evidence of disease
             progression and such participants will not be eligible for this trial

          -  The participant has received at least one prior standard and/or investigational
             regimen for metastatic disease

          -  The participant is age ≥ 18 years

          -  The participant has an Eastern Cooperative Oncology Group Performance Status (ECOG PS)
             of 0-1 (Karnofsky ≥ 80%

          -  The participant has adequate hematologic function as defined by an absolute neutrophil
             count ≥ 1500/microliter (μL), hemoglobin ≥ 9 grams/deciliter (g/dL), and a platelet
             count ≥ 100,000/μL

          -  The participant has adequate hepatic function as defined by a total bilirubin ≤ 1.5 x
             the upper limit of normal (ULN), and aspartate transaminase (AST) and alanine
             transaminase (ALT) ≤ 3 x the ULN (or ≤ 5 x the ULN in the presence of known liver
             metastases)

          -  The participant has adequate coagulation function as defined by international
             normalized ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT) ≤ 1.5 x the ULN.
             Participants on full-dose anticoagulation must be on a stable dose of oral
             anticoagulant or low molecular weight heparin, and if on warfarin must have an INR
             between 2 and 3 and have no active bleeding or pathological condition that carries a
             high risk of bleeding (for example, tumor involving major vessels or invading the
             rectal lumen, or known varices)

          -  The participant has adequate renal function as defined by serum creatinine ≤ 1.5 x the
             institutional ULN or creatinine clearance ≥ 60 milliliters/minute (mL/min) for
             participants with creatinine levels above the ULN, as well as urine protein ≤ 1+ on
             urine dipstick or routine urinalysis [(UA), if urine dipstick/routine UA indicates ≥
             2+ protein, a 24-hour urine collection for protein must demonstrate < 1000 milligrams
             (mg) of protein in 24 hours to allow participation in the study]

          -  The participant has fasting serum glucose < 120 milligrams/deciliter (mg/dL) or below
             the ULN

          -  The participant has a life expectancy of > 3 months

          -  Because the teratogenicity of IMC-A12 (cixutumumab) is not known, women of
             childbearing potential and men must agree to use adequate contraception (hormonal or
             barrier method of birth control; abstinence) prior to study entry and for the duration
             of study participation

          -  The participant has the ability to understand and the willingness to sign a written
             informed consent document

          -  The participant has a tumor that is K-ras wild-type (absence of mutations at codon 12
             or 13, as determined by the DxS K-ras Mutation Kit [polymerase chain reaction
             (PCR)-based analysis]).

          -  The participant experienced either a confirmed partial response or stable disease of ≥
             24 weeks duration during prior treatment with a cetuximab- or panitumumab-containing
             regimen except for participants with uridine diphosphate glucuronosyltransferase 1A1
             (UGT1A1) promoter polymorphism, for example, Gilbert syndrome, confirmed by genotyping
             or Invader®UGT1A1 Molecular Assay prior to enrollment. Participants enrolled with
             Gilbert Syndrome must have a total bilirubin ≤ 3 x ULN. If the participant has liver
             metastases, total bilirubin must be ≤ 3 x ULN.

        Exclusion Criteria

          -  The participant has received chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or has not recovered from
             adverse events due to agents administered more than 4 weeks earlier. Neurotoxicity, if
             present, must have recovered to National Cancer Institute Common Toxicity Criteria for
             Adverse Events (NCI-CTCAE) Version 3.0 grade ≤ 2.

          -  The participant is receiving any other investigational agent(s).

          -  The participant has a history of treatment with other agents targeting the
             insulin-like growth factor receptor (IGFR).

          -  The participant has known brain or leptomeningeal metastases.

          -  The participant has a history of primary central nervous system tumors, seizures not
             well controlled with standard medical therapy, or history of stroke within 6 months
             prior to randomization.

          -  The participant has a history of allergic reactions attributed to compounds of
             chemical or biologic composition similar to those of cetuximab or IMC-A12
             (cixutumumab).

          -  The participant has poorly controlled diabetes mellitus. Participants with a history
             of diabetes mellitus are allowed to participate, provided that their blood glucose is
             within normal range (fasting glucose < 120 mg/dL or below ULN) and that they are on a
             stable dietary or therapeutic regimen for this condition.

          -  The participant has an uncontrolled intercurrent illness including, but not limited
             to, ongoing or active infection requiring parenteral antibiotics, symptomatic
             congestive heart failure, uncontrolled hypertension, clinically significant cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  The participant is pregnant or lactating.

          -  The participant is known to be positive for infection with the human immunodeficiency
             virus.

          -  The participant is receiving therapy with immune modulators such as cyclosporine or
             tacrolimus.

          -  The participant has a history of another primary cancer, with the exception of: a)
             curatively resected nonmelanomatous skin cancer; b) curatively treated cervical
             carcinoma in-situ; or c) other primary solid tumor curatively resected treated with no
             known active disease present and no treatment administered for the last 3 years.