Conatumumab/Panitumumab Combination Metastatic Colorectal Cancer Study

Inclusion Criteria:

* Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum
* Radiographically documented disease progression per modified Response Evaluation Criteria in Solid Tumors (RECIST) during or following treatment with fluoropyrimidine, irinotecan, and/or oxaliplatin chemotherapy for Metastatic Colorectal Cancer. Progressive disease must be documented during or ≤ 6 months after the last dose of the most recent chemotherapy regimen prior to enrollment.
* At least 1 uni-dimensionally measurable lesion measuring ≥ 20 mm in one dimension per modified RECIST. Lesion must not be chosen from a previously irradiated field, unless there has been documented disease progression in that field after irradiation and prior to enrollment. All sites of disease must be evaluated.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Available archived paraffin-embedded tumor tissue from the primary tumor or metastasis for submission to the central laboratory
* Man or woman ≥ 18 years of age at the time of enrollment
* Hematologic function within the following limits:

  * Absolute neutrophil count (ANC) \> 1.0 x 10\^9 cells/L
  * Platelets ≥ 100 x 10\^9/L
* Renal function within the following limits:

  * Creatinine \< 2.0 mg/dL
* Hepatic function within the following limits:

  * Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN) (≤ 5 x ULN if liver metastases)
  * Alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases)
  * Bilirubin ≤ 2 x ULN
* Metabolic function within the following limits:

  * Amylase ≤ 2 x ULN
  * Lipase ≤ 2 x ULN
  * Magnesium ≥ lower limit of normal
* Negative pregnancy test ≤ 72 hours before enrollment (for woman of childbearing potential only)
* Must have received 1, 2, or 3 prior chemotherapy regimens for Metastatic Colorectal Cancer
* Competent to comprehend, sign, and date the independent ethics committee/institutional review board (IEC/IRB) approved written informed consent

Exclusion Criteria:

* History of other primary cancer, unless:

  * Curatively resected non-melanomatous skin cancer
  * Curatively treated cervical carcinoma in situ
  * Other primary solid tumor curatively treated with no known active disease present and no treatment administered for ≥ 5 years before enrollment
* Prior treatment with anti-epidermal growth factor receptor (EGFr) inhibitors (eg, cetuximab, erlotinib, gefitinib), unless treatment was received in the adjuvant setting ≥ 6 months before enrollment
* Use of systemic chemotherapy and radiotherapy ≤ 30 days before enrollment
* Use of prior anti-tumor therapies with a short serum half-life (less than 1 week) including prior experimental agents or approved anti-tumor small molecules ≤ 30 days before enrollment
* Use of anti-tumor therapies with a longer serum half-life (eg, bevacizumab) including prior experimental or approved protein/antibodies ≤ 42 days before enrollment
* Any investigational agent or therapy ≤ 30 days before enrollment
* Known allergy or hypersensitivity to any component of panitumumab and/or AMG 655
* History of or known presence of central nervous system (CNS) metastases
* History of interstitial lung disease (eg, pneumonitis, pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computerized tomography (CT) scan
* Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrollment
* Active inflammatory bowel disease or other active bowel disease causing chronic diarrhea (defined as ≥ Common Terminology Criteria for Adverse Events \[CTCAE\] grade 2 \[CTCAE version 3.0\])
* Known positive test for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic hepatitis B infection
* Any co-morbid disease or condition that could increase the risk of toxicity (eg, significant ascites, significant pleural effusion)
* Any uncontrolled concurrent illness (eg, infection, bleeding) or history of any medical condition that may interfere with the interpretation of the study results
* Major surgical procedure (requiring general anesthesia) ≤ 28 days or minor surgical procedure (excluding central venous catheter placement) ≤ 14 days before enrollment. Patients must have recovered from surgery related toxicities.
* Other investigational procedures are excluded
* Patient is currently pregnant or breast feeding
* Man or woman of childbearing potential who is not willing to use adequate contraceptive precautions during treatment and for 6 months (for women) or 1 month (for men) after the last investigational product administration. Adequate contraceptive precautions includes double barrier contraceptive methods (eg, diaphragm and condom) or abstinence.
* Previously enrolled into this study
* Patient unwilling or unable to comply with study requirements