This is a prospective, randomized study designed to compare genotype-guided dosing to usual care in patients with pancreas cancer and colorectal cancer who are UGT1A1 intermediate metabolizers (*1/*28) (heterozygotes) and usual UGT metabolizers (*1/*1). All patients will be assessed for UGT1A1 genotype at screening and those with intermediate or usual UGT1A1 genotypes (*1/*28, *1/*1) will be randomized to genotype-guided dosing versus usual care.

Inclusion Criteria:

• Patients must have histologically confirmed stage I-IV pancreas or stage III-IV colorectal cancer who are planning to undergo treatment.
• Prior treatment is allowed, specifically surgery and/or radiation and non-irinotecan containing regimens are allowed.
• Age ≥ 18 years.
• ECOG performance status ≤ 1.
• Patients must have adequate organ and marrow function as defined below:
• Measurable or non-measurable disease.

Exclusion Criteria:

• Patients who received prior treatment with irinotecan are excluded.
• 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 targeted therapy, in the opinion of the treating physician.
• Pregnant women are excluded from this study.
• Patients who are not planned for treatment of their cancer.