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

Repurposing Drugs as Immunotherapeutic Agents: Changes in Colorectal Tumor Immune Cells After Targeting Serotonin

This phase I trial tests whether fluoxetine (prozac) works to modify the tumor immune cells before surgery in patients with colorectal cancer. Fluoxetine is a commonly used selective serotonin reuptake inhibitor (SSRI) prescribed for major depressive disorder and generalized anxiety. Giving fluoxetine may modify the immune cell composition in the tumor and its microenvironment and may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread in patients with colorectal cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Adenocarcinoma
• Intervention / Treatment: Drug: Fluoxetine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jasmine Mitchell, MD; Phone Number: 310-825-0712; Email: jlmitchell@mednet.ucla.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA / Jonsson Comprehensive Cancer Center
      • Contact: Jasmine Mitchell, MD; Phone Number: 310-825-0712; Email: jlmitchell@mednet.ucla.edu
      • Principal Investigator: Randolph Hecht, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (fluoxetine); Patients receive fluoxetine PO once QD for 10 days prior to surgery.	Drug: Fluoxetine; Receive PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune cell composition and microenvironment	Will be assessed by changes in the immune cell composition in the tumor and its microenvironment before and after exposure to selective serotonin reuptake inhibitors therapy. Fixed tumor samples will be analyzed by immunohistochemistry for immune cell tumor infiltration and relevant lineage/activation/exhaustion markers. Will use descriptive statistics and graphical displays to compare the changes in tumor immune markers between the pre- and post-treatment tissue.	within a year of surgery

Collaborators and Investigators

• Sponsor: Jonsson Comprehensive Cancer Center
• Investigators: Principal Investigator: Randolph Hecht, MD, UCLA / Jonsson Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: January 4, 2024
• First Submitted That Met QC Criteria: January 17, 2024
• First Posted (Actual): January 25, 2024

Study Record Updates

• Last Update Posted (Actual): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Selective Serotonin Reuptake Inhibitors; Fluoxetine
• Other Study ID Numbers: 23-001744; NCI-2023-09939 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No