Mirtazapine for Cancer-related Appetite Loss

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Antidepressants

Must not be taking: Corticosteroids, Benzodiazepines

Disqualifiers: Dementia, Delirium, Pregnancy, 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: 5

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Mirtazapine, an antidepressant, can improve appetite in patients with advanced cancer experiencing significant weight loss and anorexia. Researchers aim to determine if Mirtazapine can also address common issues such as insomnia, pain, nausea, and fatigue, thereby enhancing overall quality of life. The trial compares Mirtazapine to a placebo (a non-active substance) to assess its effects. This trial may suit individuals with advanced cancer who have experienced anorexia for at least a month and have lost more than 5% of their pre-illness weight in the past six months. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

You can continue taking your current medications, including complementary therapies or cancer treatments, as long as you have been on a stable dose for at least 2 weeks and have your doctor's permission.

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

Research has shown that mirtazapine can help with appetite and weight issues related to cancer. Studies have found that it often boosts appetite and can lead to weight gain. Mirtazapine is generally well-tolerated, with common side effects like drowsiness and dry mouth, which are usually mild.

While evidence supports mirtazapine's safety, more research is needed to confirm its effectiveness and safety specifically for cancer-related symptoms. Notably, mirtazapine is already used to improve appetite in seriously ill patients, indicating some trust in its safety for similar conditions.

For those considering joining a trial with mirtazapine, these points may provide more information about its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cancer-related appetite loss?

Mirtazapine is unique because it targets appetite loss in cancer patients by acting on specific neurotransmitters in the brain, such as serotonin and norepinephrine. Unlike typical appetite stimulants that primarily focus on increasing hunger, Mirtazapine may also help improve mood and reduce nausea, which can be beneficial for cancer patients. Researchers are excited about this treatment because it offers a dual approach, potentially addressing both psychological and physical components of appetite loss, which could lead to better overall patient outcomes compared to current options.

What evidence suggests that Mirtazapine might be an effective treatment for cancer-related appetite loss?

This trial will compare Mirtazapine with a placebo to assess its effectiveness in treating cancer-related appetite loss. Research has shown that mirtazapine does not significantly increase appetite in cancer patients with anorexia. Studies found that mirtazapine works no better than a placebo, which contains no active medicine, for boosting appetite in these patients. Even when patients took mirtazapine at night for 28 days, their appetite did not improve compared to those who took a placebo. This suggests that mirtazapine might not be effective for treating appetite loss in cancer-related anorexia. ^{3 5 6 7 8}

Who Is on the Research Team?

Shalini Dalal, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adult cancer patients with anorexia and weight loss can join this trial. They must be able to consent, follow the study plan, and attend clinic visits. Pregnant women or those on certain medications like corticosteroids are excluded, as well as patients with dementia or severe depression/anxiety.

Inclusion Criteria

I can keep taking my current medications and therapies with my doctor's approval.

Ability to provide informed consent and comply with study procedures

Negative urine pregnancy test at time of inclusion into study for female patients of childbearing potential, within 24 hours of study enrollment.

Exclusion Criteria

Inability to maintain oral intake over the course of the study, such as with mechanical obstruction of the alimentary tract or intractable vomiting

I am not using benzodiazepines regularly.

I am currently on tube feeding or parenteral nutrition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive mirtazapine or placebo for 15 days, followed by dose adjustments for mirtazapine group

4 weeks

3 visits (in-person), 4 calls (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Mirtazapine
• Placebo

Trial Overview The trial is testing if Mirtazapine improves appetite in advanced cancer patients compared to a placebo. It also looks at sleep quality, pain relief, mood changes, and quality of life over about a month.

How Is the Trial Designed?

Group I: Mirtazapine Experimental Treatment 1 Intervention

Mirtazapine 15 mg by mouth (PO) daily for 15 days; Day 22-29, increased to 30 mg PO daily.

Group II: Placebo Placebo Group 1 Intervention

One placebo tablet by mouth daily.

Mirtazapine is already approved in United States, European Union for the following indications:

Approved in United States as Remeron for:

• Major depressive disorder

Approved in European Union as Avanza for:

• Major depressive episodes

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

Mirtazapine and olanzapine are effective alternatives for managing chemotherapy-related nausea, showing similar binding affinity to 5-HT3 receptors as standard treatments like ondansetron, but with longer half-lives and lower costs.

These medications not only reduce nausea but also improve sleep quality and appetite in patients with advanced cancer, suggesting they should be considered first-line treatments alongside traditional anti-nausea medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer chemotherapy and cachexia: mirtazapine and olanzapine are 5-HT3 antagonists with good antinausea effects. Kast, RE., Foley, KF.[2018]

Vandetinib is a promising new oral medication for advanced non-small cell lung cancer, shown to be safe for once-daily dosing up to 300 mg in Phase I studies.

Phase II clinical trials indicate that vandetinib may enhance treatment effectiveness when used alongside chemotherapy, with further research ongoing to explore its full potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual targeting of the vascular endothelial growth factor receptor and epidermal growth factor receptor pathways with vandetinib (ZD6474) in patients with advanced or metastatic non-small cell lung cancer. Natale, RB.[2022]

ZD6474 effectively targets two important pathways in tumor growth, inhibiting both tumor angiogenesis and cell proliferation, which suggests a dual mechanism of action in fighting cancer.

Phase I trials indicate that ZD6474 is generally well tolerated and suitable for once-daily oral dosing, with ongoing Phase II studies comparing its efficacy against standard treatments in non-small-cell lung cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ZD6474--clinical experience to date. Heymach, JV.[2023]

Vandetanib significantly increases the plasma levels of metformin and digoxin when taken together, suggesting that patients may need closer monitoring and possible dose adjustments for these medications.

No significant drug-drug interactions were observed between vandetanib and midazolam or the proton pump inhibitor omeprazole and the H2-receptor antagonist ranitidine, indicating that these combinations are likely safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic evaluations of the co-administrations of vandetanib and metformin, digoxin, midazolam, omeprazole or ranitidine. Johansson, S., Read, J., Oliver, S., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12170241/

Clinical significance of mirtazapine for anorexia in patients ... Based on the available evidence, mirtazapine does not improve outcomes in this setting. As the pathophysiology of cachexia becomes clearer, ...

2. dam.upmc.com dam.upmc.com/-/media/upmc/services/palliative-and-supportive-institute/documents/the-tablet-v4n3-new-literature_mirtazapine-for-cancerrelated-cachexia.pdf

Mirtazapine for cancer-associated anorexia and cachexia Prior RCT published in 2021 found that there was no significant difference in appetite for patients with incurable solid tumors prescribed ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0885392421003699

Mirtazapine in Cancer-Associated Anorexia and Cachexia Mirtazapine 15mg at night for 28 days is no better than placebo in improving the appetite of incurable solid tumor patients with cancer-associated anorexia and ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03254173

Mirtazapine for Treatment of Cancer Associated Anorexia ... Efficacy of mirtazapine in appetite stimulation in patients with cachexia due to advanced cancer with a change of increase of 1.5 degree on a numerical scale of ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34051293/

Mirtazapine in Cancer-Associated Anorexia and Cachexia Conclusion: Mirtazapine 15mg at night for 28 days is no better than placebo in improving the appetite of incurable solid tumor patients with cancer-associated ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7036072/

What is the evidence for mirtazapine in treating cancer-related ... The effectiveness and safety of mirtazapine in alleviating multiple symptoms in cancer populations remain unclear.

7. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2813830

Mirtazapine as Appetite Stimulant in Patients With Non– ... This randomized clinical trial assesses the effect of mirtazapine on appetite and energy consumption in patients with advanced non–small ...

8. psychiatrist.com psychiatrist.com/jcp/olanzapine-mirtazapine-rcts-cancer-related-anorexia/

Therapeutic Effects, Side Effects, and Adverse Effects of ... Mirtazapine is more likely to increase appetite and cause weight gain than selective serotonin reuptake inhibitors.23–25 These findings ...