Dasatinib for the Prevention of Oxaliplatin-Induced Neuropathy in Patients With Metastatic Gastrointestinal Cancer Receiving FOLFOX Chemotherapy With or Without Bevacizumab

Inclusion Criteria:

Confirmed confirmed stage II, III or IV colon or rectal cancer and other gastrointestinal (GI) cancers (e.g. pancreas, esophagogastric, bile duct, small bowel cancers etc) who are candidates for mFOLFOX6, with or without bevacizumab therapy. Pathological confirmation of colon,rectal or other GI cancer is required. Patients may have had prior therapy for GI cancer.
Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
Platelets >= 100 x 10^9/L
International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x upper limit of normal (ULN) unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
Serum creatinine: =< 1.5 x upper limit of normal (ULN), or measured or calculated creatinine clearance (estimated by Cockcroft-Gault formula or measured ) >= 50 mL/min urine protein:creatinine (UPC) < 2
Total bilirubin =< 2 x ULN
Aspartate aminotransferase (AST, serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT, serum glutamate pyruvate transaminase [SGPT]) =< 3 x ULN, unless evidence of liver metastases, then AST/alanine aminotransferase (ALT) =< 5 x ULN
Blood pressure (if receiving bevacizumab): systolic blood pressure (SBP) > 150 or diastolic blood pressure (DBP) > 100
Serum potassium and magnesium within the institution normal range.
Corrected QT (QTc) interval =< 450 mSec
Women of child-bearing potential must agree to use adequate contraception prior to study entry, for the duration of study participation and for 3 months after completion of study treatment administration
Prior chemotherapy in the adjuvant or metastatic setting is allowed including prior exposure to oxaliplatin in the adjuvant setting for colorectal cancer or other GI cancer as long as neuropathy is grade 1 or less.
Pre-existing neuropathy is allowed as long as it is grade 1 or less.

Exclusion Criteria:

Treatment with any other investigational agents within 4 weeks or 5 half-lives (whichever is longer) prior to the first dose of dasatinib
Gastrointestinal (GI) disease or impairment of GI function that is likely to significantly alter the absorption of dasatinib
Use of potent OCT2 and/or CYP3A4 inhibitors if treatment cannot be either safely discontinued or switched to a different medication prior to starting dasatinib
Concurrent cetuximab panitumumab or any other biological/targeted agent.
Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, known human immunodeficiency virus (HIV) diagnosis if receiving combination antiretroviral therapy, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations, including psychotic disorders, dementia and substance use disorders, that would limit compliance with study requirements
Because there is an unknown potential risk for adverse events in nursing infants secondary to treatment of the mother with dasatinib and/or oxaliplatin, breastfeeding should be discontinued
Inability to understand and sign informed consent
Any other condition that in the opinion of the investigators would make the study therapy unsafe