ExIST Study of LY2157299 (Galunisertib) in Rectal Cancer

Inclusion Criteria: * Patients (male and female) with histologically confirmed rectal adenocarcinoma, AJCC Stage IIA-IIIC or AJCC Stage IV appropriate for consideration of primary rectal tumor resection. * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Age 18 years or above. * Laboratory values (performed within 28 days prior to enrollment) as follows: * WBC ≥3.0 109/L * Hgb ≥9g/dl (patients may be transfused to reach this level) * Platelets ≥99 109 /L * Creatinine ≤1.5X upper limit of laboratory normal * AST/ALT ≤5 X upper limit of laboratory normal * Total bilirubin ≤1.5X upper limit of laboratory normal * BNP ≤ 3 times the baseline value and upper limit of laboratory normal * Troponin I ≤ upper limit of laboratory normal * hsCRP ≤ upper limit of laboratory normal * Cystatin ≤ upper limit of laboratory normal * PT/INR ≤1.5X upper limit of laboratory normal * Pre-menopausal women must have a negative pregnancy test on the day treatment starts and must avoid becoming pregnant while on treatment and for 3 months following completion of therapy. Men must avoid fathering a child while on treatment and for 3 months following completion of therapy. This exclusion is required due to the toxicities that chemotherapy, radiation, and LY2157299 may have on the forming fetus, spermatogenesis or the nursing child. Also, because pregnancy may alter immune function it may limit the treatment efficacy. Women of childbearing potential must agree to use a medically approved contraceptive method during the treatment period and for 3 months following the last dose of LY2157299. Contraceptive methods may include an intrauterine device \[IUD\], birth control pills or barrier method. If condoms are used as a barrier method, a spermicidal agent should be added as a double barrier protection. * No active bleeding. * Ability to give informed consent and comply with the protocol. Patients with a history of psychiatric illness must be judged able to understand fully the investigational nature of the study and the risks associated with the therapy. Exclusion Criteria: * Active infection requiring systemic antibiotics. * Active autoimmune disease as defined by the autoimmune disease assessment tool (see protocol) * Diagnosis of a solid tumor malignancy (excluding non-melanoma skin cancer) within 3 years of enrollment. * History of prior pelvic radiation. * Aortic aneurysm (see protocol) * Abnormal Echocardiogram (see protocol) * Immunodeficiency, need for immunosuppressive medications, or need for chronic steroids. * Participation in any investigational drug study within 28 days of enrollment. * Pregnant or lactating women, as treatment involves risks to the embryo or fetus. * Other medical or psychiatric conditions that in the opinion of the Principal Investigator would preclude safe participation in protocol. * History of cardiac disease, including myocardial infarction within 6 months before study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension, major cardiac abnormalities, a predisposition for developing aneurysms including family history of aneurysms, Marfan syndrome, bicuspid aortic valve, or evidence of damage to the large vessels of the heart. * Concomitant use of strong CYP3A4 inhibitors and inducers