Local Consolidative Therapy in Colorectal Cancer

Inclusion Criteria:

* Subjects must have histologically or cytologically confirmed metastatic colorectal cancer with 1-3 active metastatic lesions irrespective of location. Previously locally treated (e.g. radiation or interventional radiology-based ablated) metastases that have had a 6-month progression free interval per imaging exams, do not count toward the 1-3 active metastases. Adjacent lymph nodes in the same region constitute one active lesion.
* Subjects must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v. 1.1 as described in detail in section 12.0.
* All sites of metastatic disease must be amenable to either surgical resection or stereotactic body radiotherapy (SBRT).
* The primary lesion may be either intact or previously resected, but if intact must be resected as part of LCT (primary does not count as one of 1-3 sites of metastatic disease).
* Subjects must have received at least one prior line of systemic therapy with a fluoropyrimidine-based regimen for metastatic disease and be candidates for further systemic chemotherapy. Front-line therapy could have been discontinued for disease progression, unacceptable toxicity, or drug holiday, provided that the therapy was discontinued less than six months from study enrollment.
* Age \> 18 years.
* ECOG performance status 0 or 1
* Subjects must have normal organ and marrow function as defined below

  * Absolute neutrophil count \> 1,500/mcL
  * Platelets \> 100,000/mcL
  * Total bilirubin \< 2 mg/dL
  * AST/ALT (SGOT/SGPT) \< 5X ULN
  * Creatinine \< 1.5X ULN OR
  * Creatinine clearance \< 50 ml/min/1.73 m2 for subjects with creatinine levels above institutional normal
* Subjects must possess the ability to understand and willingness to sign a written informed consent and HIPAA consent document.

Exclusion Criteria:

* Subjects must not be experiencing toxicity due to prior therapy that has not resolved to ≤Grade 1 by study registration, with the exception of sensory neuropathy related to previous oxaliplatin exposure, alopecia and fatigue.
* \>Grade 2 sensory neuropathy
* Subjects must not be receiving any other investigational agents.
* Subjects must not have known central nervous system (CNS) metastases and/or carcinomatous meningitis, either untreated or treated.
* Subjects must not be unfit to receive combination therapy (\>/=2 drugs that could include one biologic agent) as determined by the treating physician.
* Subjects must be able to undergo surgical resection and/or SBRT.
* Subjects must not have 4 or more active metastatic sites.
* Subjects must not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Any condition or significant co-morbidity that prevents safe surgery or delivery of SBRT
* Subjects must not be pregnant or breast feeding. Refer to section 4.4 for further detail.