Duloxetine for Colorectal Cancer

Not currently recruiting at 880 trial locations

Overseen By Chaoyuan Kuang

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Alliance for Clinical Trials in Oncology

Must be taking: Oxaliplatin

Must not be taking: Antidepressants, MAOIs, Warfarin, Heparin

Disqualifiers: Peripheral neuropathy, Seizure disorder, Glaucoma, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 30

Duration: 17 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether duloxetine, commonly used for depression and pain, can prevent pain, tingling, and numbness in patients with stage II-III colorectal cancer receiving the chemotherapy drug oxaliplatin. Duloxetine increases certain chemicals in the brain. The trial includes different groups to determine the best dose and assess effectiveness. It suits patients with colorectal cancer who will receive oxaliplatin and have not experienced similar nerve issues before. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, allowing patients to contribute to important research.

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications. You cannot use other drugs for peripheral neuropathy, certain antidepressants, or serotonin-altering agents. Some medications must be stopped at least 7 to 14 days before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that duloxetine is generally safe for use. It often helps with pain and symptoms like tingling and numbness associated with chemotherapy. Studies indicate that duloxetine is sometimes used off-label to treat nerve pain from cancer treatments with drugs like paclitaxel and docetaxel. This suggests it might also help with similar symptoms from other cancer treatments like oxaliplatin.

Duloxetine has been tested on many people, and most can take it without serious issues. However, like any medication, it can have side effects. Some people experience nausea, dry mouth, or tiredness. Rarely, it may cause more serious problems, so regular check-ups during treatment are important.

The FDA addressed a recall due to a possible cancer-causing chemical in one batch, but this was a specific issue. Discussing any concerns with a doctor is always advisable, but overall, duloxetine's safety is well understood from years of use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for colorectal cancer, which typically involve chemotherapy, radiation, and surgery, duloxetine is primarily known as an antidepressant and works by influencing serotonin and norepinephrine in the brain. Researchers are excited about duloxetine for colorectal cancer because it offers a novel approach to potentially managing symptoms or enhancing quality of life for patients, which traditional cancer treatments may not address directly. Additionally, if duloxetine demonstrates effectiveness in this new role, it could provide a less invasive treatment option with a different side effect profile compared to conventional cancer therapies.

What evidence suggests that duloxetine could be effective in preventing peripheral neuropathy in colorectal cancer patients?

This trial will evaluate duloxetine's effectiveness in preventing chemotherapy-induced peripheral neuropathy (CIPN) in colorectal cancer patients. Studies have shown mixed results regarding duloxetine's ability to prevent CIPN, which includes symptoms like pain, tingling, and numbness. Research suggests that duloxetine can help manage pain and aid recovery after some surgeries. However, other studies found duloxetine no more effective than a placebo in preventing tingling and numbness from chemotherapy. It increases certain brain chemicals that help reduce pain and depression. While some evidence supports its use for pain relief, its effectiveness in preventing CIPN remains uncertain. Participants in this trial will be assigned to different groups, including those receiving duloxetine and those receiving a placebo, to further investigate its potential benefits. ^{1 2 6 7 8}

Who Is on the Research Team?

Ellen M. Lavoie Smith, PhD

Principal Investigator

The University of Alabama at Birmingham School of Nursing

Are You a Good Fit for This Trial?

This trial is for stage II-III colorectal cancer patients who are about to receive oxaliplatin treatment and have no prior neurotoxic chemotherapy, pre-existing neuropathy, seizure disorders, glaucoma, severe psychiatric conditions or substance abuse. They must not be on certain medications like MAOIs or strong CYP1A2 inhibitors and should not be pregnant.

Inclusion Criteria

I have stage II-III colorectal cancer and will start a specific chemotherapy regimen soon.

No serious eating disorder such as bulimia or anorexia

No known diagnosis of ethanol (ETOH) addiction/dependence within the past 10 years

Exclusion Criteria

I am not taking medications like gabapentin for nerve pain and can stop them 7 days before treatment.

I stopped taking MAOI or other antidepressants 14 days before starting the treatment.

I am not taking strong medications that affect liver enzymes CYP1A2 and CYP2D6.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive duloxetine or placebo alongside standard oxaliplatin treatment to prevent peripheral neuropathy

17 weeks

Weekly visits for monitoring and administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

Follow-up visits at 30 days, 3, 6, 12, and 18 months post-treatment

What Are the Treatments Tested in This Trial?

Interventions

• Duloxetine

Trial Overview

The trial is testing whether duloxetine can prevent peripheral neuropathy (pain, tingling, numbness) in patients receiving oxaliplatin for colorectal cancer. It involves comparing the effects of duloxetine with a placebo while monitoring quality-of-life through questionnaires.

How Is the Trial Designed?

Group I: Phase III, Arm I (duloxetine hydrochloride) Experimental Treatment 5 Interventions

Patients in Phase III receive most promising dose of duloxetine hydrochloride from Phase II PO QD in the absence of unacceptable toxicity.

Group II: Phase II, Arm II (duloxetine hydrochloride) Experimental Treatment 5 Interventions

Patients in Phase II receive duloxetine hydrochloride 30 mg (1 duloxetine capsule) orally (PO) once daily (QD) during week 1, duloxetine hydrochloride 60 mg (2 duloxetine capsules) PO QD during weeks 2-16, followed by duloxetine hydrochloride 30 mg (1 duloxetine capsule) PO QD during week 17 in the absence of unacceptable toxicity.

Group III: Phase II, Arm I (duloxetine hydrochloride, placebo) Experimental Treatment 6 Interventions

Patients in Phase II receive duloxetine hydrochloride 30 mg (1 duloxetine capsule) orally (PO) once daily (QD) during week 1, duloxetine hydrochloride 30 mg (1 duloxetine capsule) PO QD and placebo (1 placebo capsule) PO QD during weeks 2-16, followed by duloxetine hydrochloride 30 mg (1 duloxetine capsule) PO QD during week 17 in the absence of unacceptable toxicity.

Group IV: Phase II, Arm III (placebo) Placebo Group 4 Interventions

Patients in Phase II receive placebo (1 placebo capsule) orally (PO) once daily (QD) during week 1, placebo (2 placebo capsules) PO QD weeks 2-16, followed by placebo (1 placebo capsule) PO QD during week 17 in the absence of unacceptable toxicity.

Group V: Phase III, Arm II (placebo) Placebo Group 4 Interventions

Patients in Phase III receive placebo PO QD in the absence of unacceptable toxicity.

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The maximum tolerated dose (MTD) for the combination of erlotinib, capecitabine, and oxaliplatin in metastatic colorectal cancer (MCRC) was established as capecitabine 825 mg/m² twice daily, oxaliplatin 130 mg/m² on day 1, and erlotinib 100 mg daily, with the regimen showing good tolerability and no unexpected adverse events.

Antitumor activity was observed in the trial, with one complete response, four partial responses, and stable disease in 11 patients, indicating that this combination therapy may be effective and warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase Ib dose-escalation study of erlotinib, capecitabine and oxaliplatin in metastatic colorectal cancer patients. Van Cutsem, E., Verslype, C., Beale, P., et al.[2020]

The XELOX30 regimen, which combines capecitabine and a shorter 30-minute infusion of oxaliplatin, was tested in 70 patients with advanced colorectal cancer resistant to irinotecan, showing a response rate of 17% and a median survival of 9.5 months.

The treatment demonstrated a moderate level of neurotoxicity, with 56% of patients experiencing grade 1 and 17% grade 2 neuropathy, indicating that XELOX30 is a convenient and effective second-line therapy with a safety profile comparable to longer infusion schedules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-time infusion of oxaliplatin in combination with capecitabine (XELOX30) as second-line therapy in patients with advanced colorectal cancer after failure to irinotecan and 5-fluorouracil. Pfeiffer, P., Sørbye, H., Ehrsson, H., et al.[2020]

In a large post-marketing surveillance study of 301 patients with colorectal cancer, gastrointestinal stromal tumors, and hepatocellular carcinoma, regorafenib was found to have a high incidence of adverse events (85% for CRC), with palmar-plantar erythrodysesthesia syndrome being the most common side effect, but no new safety concerns were identified.

The effectiveness of regorafenib varied by cancer type, showing an overall response rate of 4.7% for CRC, 0% for GIST, and 41.4% for HCC, with median progression-free survival of 2.1 months for CRC and 9.2 months for GIST, indicating that while it is generally safe, its efficacy can differ significantly among different cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of safety and effectiveness of regorafenib for treatment of metastatic colorectal cancer, advanced gastrointestinal stromal tumors, and hepatocellular carcinoma: a post-marketing surveillance study in Korea. Beom, SH., Bae, KB., Zang, DY., et al.[2022]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/37194004/

Efficacy of perioperative duloxetine as a part of multimodal ...

Perioperative duloxetine had reduced postoperative pain, decreased opioid consumption, and improved the quality of recovery in patients undergoing laparoscopic ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12494338/

A Retrospective Analysis of 14 Antineoplastic Agents - PMC

Of the 156 patients dispensed paclitaxel, 62 (40%) were dispensed with duloxetine compared to 43 (28%) with venlafaxine. Of the 70 patients ...

3.

cdn.mdedge.com

cdn.mdedge.com/files/s3fs-public/issues/articles/0825FED%20AVAHO%20Antidepress_0.pdf

A Retrospective Analysis of 14 Antineoplastic Agents

Among these,. 201 patients (36%) received both anticoagulants and antidepressants: duloxetine for 64 patients, venlafaxine for 30, trazodone for ...

4.

firstwordpharma.com

firstwordpharma.com/story/5965717

Duloxetine Does Not Prevent Chemotherapy-Induced ...

Researchers were unable to show that the serotonin–norepinephrine reuptake inhibitor duloxetine is more beneficial than placebo in preventing CIPN.

5.

studypages.com

studypages.com/s/duloxetine-to-prevent-chemo-induced-numbness-tingling-in-stage-ii-iii-colon-cancer-146053/

Duloxetine to Prevent Chemo-Induced Numbness & ...

This clinical trial studies the best dose of duloxetine and how well it works in preventing pain, tingling, and numbness (peripheral neuropathy)

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC2962879/

Colorectal cancer risk in relation to antidepressant medication ...

A recent study noted a reduced risk of colorectal cancer associated with SSRI use and a non-significant reduction with TCA use.

7.

emjreviews.com

emjreviews.com/neurology/news/duloxetine-recalled-due-to-cancer-risks/

Duloxetine Recalled Due to Cancer Risks

The FDA has classified a recall of Duloxetine due to N-nitroso-duloxetine, a potentially cancer-causing chemical.

8.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2004/21427lbl.pdf

Cymbalta® (duloxetine hydrochloride) - accessdata.fda.gov

Duloxetine has been evaluated for safety ... tabulated results from placebo controlled trials appear in this listing); infrequent adverse events.