Phase I Trial of Ganetespib, Capecitabine, and Radiation in Rectal Cancer

Inclusion Criteria: * Must be at least 18 years of age * Stage II or III histologically-proven rectal adenocarcinoma. The distal border of the tumor must be at or below the peritoneal reflection, defined as within 12 centimeters of the anal verge by proctoscopic examination. * Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 * Adequate hematologic function as defined by: * Absolute neutrophil count ≥ 1,500 cells/µL * Platelets ≥ 100,000/µL * Hemoglobin ≥ 9.0g/dL * Adequate hepatic function as defined by: * Total bilirubin ≤ 1.5 x the upper limit of normal (ULN) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN * Albumin ≥ 3.0 g/dL * Adequate renal function as defined by: * Serum creatinine ≤ 1.5 x ULN * Calculated creatinine clearance of ≥ 50 mL/min * International normalized ratio (INR) ≤ 1.5. Anticoagulation is allowed only with low molecular weight heparin (LMWH). Patient receiving LMW heparin on stable therapeutic dose for more than 2 weeks or with factor Xa level \< 1.1 U/mL are allowed on the trial. * Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures * Ability to understand and willingness to sign a written informed consent document * Female subjects of childbearing potential and males must agree to use adequate contraception (e.g., hormonal or barrier method of birth control; abstinence) for the duration of study treatment * Female subjects of childbearing age must have a negative serum pregnancy test at study entry. Exclusion Criteria: * History of previous radiation therapy to the abdomen or pelvis * History of previous chemotherapy for rectal cancer * Major surgery within 4 weeks prior to first dose of ganetespib * Poor venous access for study drug administration. The study drug must be administered via peripheral venous access or through vascular access devices (VADs) (such as ports and peripherally-inserted central catheters \[PICCS\] containing silicone catheters. Use of VADs with catheters made of any other material is not allowed. * History of severe allergic or hypersensitivity reactions to excipients (e.g., Polyethylene glycol \[PEG\] 300 and Polysorbate 80) * Baseline corrected QT interval (QTc) \> 450 msec or previous history of QT prolongation while taking other medications * Ventricular ejection fraction (Ef) ≤ 55% at baseline * Treatment with chronic immunosuppressants (e.g., cyclosporine following transplantation) * Women who are pregnant or lactating * Uncontrolled intercurrent illness * 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 subject inappropriate for entry into this study * Patients must be able to take oral medications. * Unequivocal metastatic disease on computed tomography or chest X-ray * Clinically significant comorbid conditions such as cardiovascular disease or significant peripheral vascular (e.g., uncontrolled hypertension, myocardial infarction, unstable angina) within 6 months of study entry, serious cardiac arrhythmia requiring medication, and uncontrolled infection. * Clinical evidence of bleeding diathesis or coagulopathy * Significant involvement of the bladder by the tumor * Patients with prior malignancies, including pelvic cancer, are eligible if they have been disease free for \> 5 years. Patients with prior in situ carcinomas are eligible provided there was complete removal.