Fluoxetine for Colorectal Cancer

Overseen By Jasmine Mitchell, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Jonsson Comprehensive Cancer Center

Must be taking: Fluoxetine

Must not be taking: Tamoxifen, Pimozide, Thioridazine, others

Disqualifiers: Metastatic cancer, Neoadjuvant chemotherapy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 10 days

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether fluoxetine (commonly known as Prozac) can alter immune cells in tumors for individuals with colorectal cancer. The goal is to determine if it can prevent cancer cells from growing and spreading before surgery. Individuals with colorectal cancer who haven't received treatment and don't require pre-surgery therapy might be suitable candidates.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

Will I have to stop taking my current medications?

If you are currently taking tamoxifen, pimozide, thioridazine, or any antidepressants like SSRIs, SNRIs, MAOIs, or lithium, you will need to stop these medications to participate in the trial.

Is there any evidence suggesting that fluoxetine is likely to be safe for humans?

Research shows that fluoxetine, also known as Prozac, is generally safe for use. This popular antidepressant has been prescribed for many years to treat depression and anxiety. Studies have not found a link between fluoxetine and a higher risk of colorectal cancer. In fact, some patients taking fluoxetine showed a lower chance of developing colon cancer, although experts continue to discuss its effects.

Researchers are now testing fluoxetine in early studies to see if it can help change immune cells in patients with colorectal cancer. This means limited information exists about its safety for this specific use. However, the FDA's approval for other conditions suggests a certain level of safety. Always discuss the benefits and risks with your doctor before joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for colorectal cancer involve surgery, chemotherapy, and radiation, targeting cancer cells directly. However, fluoxetine, commonly known as an antidepressant, is being explored for its potential to affect cancer growth differently. Researchers are excited because fluoxetine may influence cancer cell behavior by altering serotonin pathways, which are not typically targeted in colorectal cancer treatment. This new approach could offer a supplementary method to weaken cancer cells before surgery, potentially improving outcomes.

What evidence suggests that fluoxetine might be an effective treatment for colorectal cancer?

Research has shown that fluoxetine, an antidepressant also known as Prozac, might help lower the risk of colon cancer. Some studies found that people taking fluoxetine had a reduced chance of developing colon cancer, with one study reporting up to a 50% decrease in risk. Fluoxetine may alter the immune cells around the tumor, making it harder for cancer cells to grow and spread. Additionally, fluoxetine has triggered a process called apoptosis, where cancer cells are programmed to die, potentially stopping tumor growth. While fluoxetine primarily treats depression, these findings suggest it might also play a role in cancer treatment. Participants in this trial will receive fluoxetine before surgery to evaluate its potential effects on colorectal cancer. ^{1 5 6 7 8}

Who Is on the Research Team?

Jasmine Mitchell, MD

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with colorectal cancer who are scheduled for surgery. The study is exploring if fluoxetine, a medication typically used for depression and anxiety, can alter immune cells in the tumor before surgery.

Inclusion Criteria

Platelets ≥ 100x10^9/L

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

Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT]) / alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 x ULN

Exclusion Criteria

I have been diagnosed with advanced colorectal cancer.

I have had chemotherapy before my planned colon cancer surgery.

I have no active cancer other than skin cancer (not melanoma) in the past 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fluoxetine orally once daily for 10 days prior to surgery

10 days

Follow-up

Participants are monitored for changes in immune cell composition and activity after treatment

up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Fluoxetine

Trial Overview The trial is testing fluoxetine's effect on modifying tumor immune cells in colorectal cancer patients. It aims to see if this common antidepressant can change the immune environment of the tumor and potentially hinder cancer growth and spread.

How Is the Trial Designed?

Group I: Treatment (fluoxetine) Experimental Treatment 1 Intervention

Patients receive fluoxetine PO once QD for 10 days prior to surgery.

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Published Research Related to This Trial

Approximately 50% of colorectal cancer patients develop metastatic disease, but long-term disease-free survival can be achieved in 25% to 40% of selected patients who undergo resection of liver or lung metastases.

New treatments like irinotecan and oxaliplatin, along with novel therapies such as targeted inhibitors and local interventions, have improved survival and quality of life for colorectal cancer patients, moving beyond the traditional use of 5-fluorouracil.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metastatic colorectal cancer. Kindler, HL., Shulman, KL.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3936192/

Antidepressant fluoxetine and its potential against colon ... Patients treated with fluoxetine (FLX) have a reduced incidence of colon cancer, although there still remains great controversy about the nature of its effects.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26004136/

Oncostatic effects of fluoxetine in experimental colon ... Recent studies have shown a reduced risk for colon cancer in patients given the antidepressant fluoxetine (FLX).

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0014299919303929

Fluoxetine selectively induces p53-independent apoptosis ... In some clinical studies, a 50% reduction of risk of colon cancer was reported in patients treated with fluoxetine (Coogan et al., 2009).

4. mdpi.com mdpi.com/1422-0067/25/12/6314

Potential Repurposing of Fluoxetine toward Cancer Therapy Different psychotropic drugs, including fluoxetine, fluspirilene, ebastine, and aripiprazole, demonstrated anticancer activity in glioblastoma, colorectal ...

5. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0050043

Antiproliferative Effects of Fluoxetine on Colon Cancer Cells ... In vivo, fluoxetine reduced the development of MNNG-induced dysplasia and vascularization-related dysplasia in colon tissue, which was analyzed by ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06225011

Fluoxetine for the Modification of Colorectal Tumor Immune ... 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 ...

7. journals.lww.com journals.lww.com/md-journal/fulltext/2020/05290/antidepressant_use_and_colorectal_cancer_morbidity.28.aspx

Antidepressant use and colorectal cancer morbidity and... The results showed antidepressant use was not associated with colorectal cancer mortality (RR: 1.08; 95% CI: 0.99–1.17). F3 Figure 3: Forest ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032716309284

Antidepressants and colorectal cancer: A population-based ... Contemporary first-line antidepressants (ie SSRI, SNRI), as well as older agents (ie TCA), are not associated with increased incidence of colorectal cancer.