Fluoxetine for the Modification of Colorectal Tumor Immune Cells Before Surgery in Patients With Colorectal Cancer

PRIMARY OBJECTIVE:

I. To evaluate alterations in tumor immune cell composition and activity under SSRI treatment.

OUTLINE:

Patients receive fluoxetine orally (PO) once daily (QD) for 10 days prior to surgery.

Inclusion criteria

• Male or female ≥ 18 years of age at visit 1
• Previously untreated cytologically or histologically confirmed colorectal adenocarcinoma that will not need neoadjuvant therapy
• Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study
• World Health Organization (WHO) Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count (ANC) ≥ 1.5x10^9/L
• Platelets ≥ 100x10^9/L
• Hemoglobin ≥ 9 g/dL
• Serum creatinine (sCr) ≤ 1.5 x upper limit of normal (ULN)
• Creatinine clearance (Ccr) ≥ 40 mL/min (as calculated by Modified Cockcroft-Gault formula)
• Serum total bilirubin ≤ 1.5 x ULN
• Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT]) / alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 x ULN
• Baseline corrected QT (QTc) within normal limits per the Bazett formula. Any electrocardiogram (EKG) done prior to consent is acceptable for baseline QTc monitoring.

• Normal QTc ranges from 350-450 ms for adult men and from 360-460 ms for adult women

Exclusion criteria

• Presence of a condition or abnormality that in the opinion of the investigator would compromise the safety of the participant or the quality of the data
• A diagnosis of metastatic colorectal adenocarcinoma
• Individuals who have received neoadjuvant chemotherapy prior to the planned colon cancer resection
• Individuals with absolute or relative contraindications to fluoxetine

• Baseline prolonged QTc
• Concurrently taking tamoxifen, pimozide, or thioridazine
• Individuals using other SSRIs, serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), lithium or other antidepressants at time of initial biopsy
• Currently active second primary malignancy or history of malignancy less than 5 years prior to the time of study eligibility (Patients with history of skin cancers excluding melanoma will be eligible for participation)