To learn if lifestyle changes (such as diet and exercise) combined with daily aspirin and vitamin D can affect the likelihood of advanced colorectal cancer coming back (recurring)

Primary Objective:

To estimate the ctDNA clearance rate of colorectal cancer participants with minimal residual disease after 3 months of optimal lifestyle interventions

Secondary Objectives:

• To evaluate the dynamics of ctDNA allele fractions after 3 months of optimal lifestyle interventions and every 3 months thereafter up to 12 months
• To estimate the recurrence rate at 1 year in subjects who complete 3 months of optimal lifestyle interventions

Inclusion Criteria:

• Age ≥ 18 years at the time of study entry
• ECOG 0-1
• Histologically documented high-risk stage II, stage III, or stage IV colorectal adenocarcinoma with no evidence of disease following definitive local therapy (including surgical resection or ablation)
• No radiographic evidence of disease by contrast enhanced CT chest/abdomen/pelvis
• Presence of detectable ctDNA mutation that matches mutations found in tumor tissue
• Completion of all standard of care adjuvant therapy
• Platelet count >50,000
• Ability to give informed consent
• Ability to complete all questionnaires involved in study

Exclusion Criteria:

• Concurrent malignancy under active treatment
• Known active gastrointestinal bleeding or peptic ulcer disease
• Known hypersensitivity to vitamin D or aspirin
• CrCl<30 mL/min within 30 days of starting the intervention
• Current usage of therapeutic anticoagulation (warfarin, Eliquis, Xarelto)
• Inability to safely participate in physical activity in the opinion of the treating oncologist
• Pregnant or nursing women. N.B.: urine pregnancy test will be administered as part of the screening process.
• Persistent hypercalcemia or conditions predisposing to hypercalcemia (i.e., hyperparathyroidism)
• Known symptomatic genitourinary stones