The purpose of this study is to find out what effects, good and/or bad STA-9090 has on colorectal cancer. This is a phase II trial which tests both how well the drug works in fighting your cancer as well as any possible side effects it will have on the patient.

Cancer is a disease of uncontrolled growth. This growth is controlled in part by a series of proteins that are part of a growth pathway. Some of these proteins are destroyed by a protein called HSP90 and STA-9090 is a test drug which blocks one of the proteins that helps cancer grow. This study will also look at molecular markers that may affect how the cancer grows, and how it responds to treatment.

Inclusion Criteria:

• The patient has histologically or cytologically-confirmed colorectal cancer with metastatic disease documented on diagnostic imaging studies.
• The patient 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 ≥20 mm on conventional measurement techniques or ≥10 mm on spiral computed tomography (CT) scan.
• The patient has received at least one prior standard and/or investigational regimen for metastatic disease.
• The patient is age ≥18 years.
• The patient has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 (Karnofsky≥ 80%).
• The patient has adequate hematologic function as defined by an absolute neutrophil count ≥1500/μL, hemoglobin ≥9/μdL, and a platelet count ≥100,000/μL.
• The patient has adequate hepatic function as defined by a total bilirubin ≤ 2.5x 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 patient, if not on anticoagulation, has adequate coagulation function as defined by international normalized ratio (INR) ≤1.5 ULN and partial thromboplastin time (PTT) ≤1.5x the ULN. Patients on full-dose anticoagulation must be on a stable dose of oral anticoagulation or low molecular weight heparin, must have an INR value within acceptable range for treatment and have no active bleeding or pathological condition that, in the opinion of the investigator, carries a high risk of bleeding.
• The patient has adequate renal function as defined by serum creatinine ≤1.5 x the institutional ULN or creatinine clearance ≥60 mL/min for patients with creatinine levels above 1.5, as well as urine protein ≤1+ on routine analysis (if routine UA indicates ≥2+ protein, a 24-hour urine collection for protein must demonstrate < 1000mg of protein in 24 hours to allow participation in the study).
• The patient has a life expectancy of > 3 months.
• Because the teratogenicity of STA-9090 is not known, men and women of childbearing potential must agree to use adequate contraception (hormonal or barrier birth control; abstinence) prior to study entry and for the duration of study participation.
• The patient has the ability to read and willingness to sign informed consent.
• For stage I of the protocol (the first 15 patients) the tumor must be amenable to biopsy and the patient must be willing to undergo pre and post treatment biopsies.
• The patient must have a normal QTc interval on baseline ECG , (<470 milliseconds, males and females).

Exclusion Criteria:

• Patient may not have received chemotherapy within 4 weeks prior to entering the study, and must have recovered (to grade 1 or less) from adverse events due to agents administered.
• Primary brain tumors or active brain metastases. However, patients with a history of CNS metastases will be eligible if they have been treated and are stable for 4 weeks after completion of treatment, with image documentation required, and must be either off steroids or on a stable dose of steroids for a minimum of 2 weeks prior to enrollment.
• History of stroke within 6 months of treatment or other significant neurological limitations.
• Major surgery within 4 weeks prior to entering the study.
• Poor venous access for study drug administration or would require a peripheral or central indwelling catheter for study drug administration. Study drug administration via indwelling catheters is prohibited at this time.
• Use of any investigational agents within 4 weeks prior to entering the study.
• History of severe allergic reactions to excipients (e.g., Polyethylene glycol 300 and Polysorbate 80), including severe hypersensitivity reactions defined as ≥ Grade 3 based on NCI CTCAE version 3.
• Treatment with chronic immunosuppressants (e.g., cyclosporine following transplantation or systemic steroids for treatment of autoimmune disease). However, patients may receive steroids for stable CNS metastases as described in exclusion criterion 2.
• Uncontrolled intercurrent illness including, but not limited to, human immunodeficiency virus (HIV)-positive patients receiving combination antiretroviral therapy, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, ventricular arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Other medications, or severe acute/chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.
• Ventricular ejection fraction (Ef) ≤ 45%.
• Inaccessible tissue for biopsy (first 15 patients only)
• History of or current coronary artery disease, myocardial infarction, angina pectoris, angioplasty or coronary bypass surgery
• History of or current uncontrolled dysrhythmias, or requirement for antiarrhythmic medications, or Grade 2 or greater left bundle branch block
• New York Heart Association class II/III/IV congestive heart failure with a history of dyspnea, orthopnea or edema that requires current treatment with angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers or diuretics
• Current or prior radiation therapy to the left hemithorax