Olanzapine and Mirtazapine for Weight Loss in Advanced Stage Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Englewood Hospital and Medical Center

Must not be taking: Marinol

Disqualifiers: Abnormal liver function, Elevated QTc, TPN/enteral feeds, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether olanzapine or mirtazapine better prevents weight and appetite loss in individuals with advanced cancer. Researchers are testing both drugs to assess their effectiveness in maintaining weight during cancer treatment. This trial may suit individuals with advanced cancer who have experienced more than 5% unintentional weight loss over the past 3-6 months, despite following standard nutritional advice and using supplements. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to important research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take Marinol within two weeks of joining the study. Patients on Dexamethasone are allowed to participate.

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

Research has shown that both olanzapine and mirtazapine are generally well-tolerated by people with advanced cancer. Olanzapine effectively reduces nausea and vomiting in cancer patients and is considered relatively easy for most to take. One study found that patients could take up to 20 mg without major problems.

Mirtazapine is also regarded as a safe choice for those with cancer. It is primarily processed by the liver and helps with several cancer-related symptoms. Studies suggest that most patients handle mirtazapine well and may benefit from its various effects.

Both treatments are generally manageable for patients, with few reports of serious side effects. This suggests they might be safe options for managing weight loss and appetite issues in advanced cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using olanzapine and mirtazapine for weight loss in advanced stage cancer patients because these drugs offer a novel approach compared to traditional treatments. While current options typically focus on managing symptoms with nutritional support and appetite stimulants, olanzapine and mirtazapine have unique properties that may help address weight loss more effectively. Olanzapine, primarily an antipsychotic, has been observed to influence weight gain by altering metabolism and appetite pathways. Mirtazapine, an antidepressant, is known for its side effects of increased appetite and weight gain. By repurposing these medications, researchers hope to provide a dual benefit of mood enhancement and weight stabilization, which could significantly improve the quality of life for cancer patients.

What evidence suggests that this trial's treatments could be effective for weight loss in advanced stage cancer?

Research has shown that olanzapine, one of the treatments in this trial, can cause noticeable weight gain in cancer patients, even at low doses like 2.5 mg per day. This suggests it might help address weight loss issues in people with advanced cancer. In contrast, studies have shown mixed results for mirtazapine, another treatment option in this trial. Some patients with advanced cancer gained weight, but their appetite did not clearly improve. Thus, while olanzapine seems promising for weight gain, mirtazapine's effectiveness remains less certain. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with advanced cancer who have lost more than 5% of their weight unintentionally over the last 3-6 months, despite nutritional support. They must be able to consent, communicate effectively, and have a life expectancy of at least 4 months. Those on dexamethasone or undergoing chemotherapy can join. People using Marinol recently, with abnormal heart rhythms or liver function, or primarily fed intravenously cannot participate.

Inclusion Criteria

You have lost more than 5% of your body weight over the last 3-6 months without trying to lose weight. This is not due to just not eating, and has not improved with standard nutrition advice and supplements for at least 2 weeks.

Able to provide informed consent

Pathologically and/or clinically confirmed diagnosis of advanced cancer

Exclusion Criteria

You have taken Marinol within two weeks before joining the study.

Elevated QTc (EKG performed within 1 year of enrollment will be accepted)

Total parental nutrition (TPN) or enteral feeds (PEG/PEJ) for >70% of their primary source of daily calorie intake

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Olanzapine or Mirtazapine to assess their effectiveness in preventing weight and appetite loss

6 months

Monthly visits for weight measurement

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mirtazapine
• Olanzapine

Trial Overview The study aims to compare the effectiveness of two medications, Olanzapine and Mirtazapine, in preventing further weight loss and appetite loss in patients with advanced stage cancer. It will assess which drug better helps manage these symptoms associated with cancer.

How Is the Trial Designed?

Group I: Olanzapine Experimental Treatment 1 Intervention

Group II: Mirtazapine Experimental Treatment 1 Intervention

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?

Englewood Hospital and Medical Center

Lead Sponsor

Trials

21

Recruited

770+

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03254173

Mirtazapine for Treatment of Cancer Associated Anorexia ... Efficacy of mirtazapine in weight gain in patients with cachexia due to advanced cancer. ''Improved'' weight will be defined as a gain of ≥ 1 kg and '' ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00832520

Phase II Study of Remeron for Cancer Patients Losing ... Therefore, using mirtazapine in cancer patients even without depression may help to stop unwanted weight loss and increase survival by allowing patient to ...

3. cdn.amegroups.cn cdn.amegroups.cn/journals/pbpc/files/journals/2/articles/100804/public/100804-PB4-3338-R2.pdf?filename=jtd-17-05-3478.pdf&t=1757432981

Clinical significance of mirtazapine for anorexia in patients ... In a study including 20 patients with advanced-stage cancer, the data did not reveal significant changes in appetite, despite a weight gain of.

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

Clinical significance of mirtazapine for anorexia in patients ... In a study including 20 patients with advanced-stage cancer, the data did not reveal significant changes in appetite, despite a weight gain of ≥ ...

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

What is the evidence for mirtazapine in treating cancer-related ... The study did not find any significant difference for weight or fatigue across the different arms. Oszoy et al. report an open-labelled study ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02650544

Efficacy and Safety Analyses of Mirtazapine in NSCLC ... Study objective is to assess the efficacy and safety of mirtazapine in advanced NSCLC patients with malignant tumor related depression. Study hypothesis is that ...

7. bmcpalliatcare.biomedcentral.com bmcpalliatcare.biomedcentral.com/articles/10.1186/s12904-022-00976-7

What is the effectiveness and safety of mirtazapine versus ... Mirtazapine, an antidepressant agent, has been suggested as a potential relevant drug to alleviate multiple cancer-related symptoms at a same time.

8. jpsmjournal.com jpsmjournal.com/article/S0885-3924(11)00320-4/fulltext

Intolerance to Mirtazapine in Advanced Cancer Therefore, we anticipated that advanced cancer patients would tolerate mirtazapine relatively well and might benefit from its several effects. However, there ...

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

Therapeutic Effects, Side Effects, and Adverse Effects of ... Cancer was advanced (stage IV) in about 80% of the sample. About 90% of patients reported anorexia at baseline, and nearly a third were ...