Mirtazapine for Brain Tumor

Overseen By UC Irvine Health Chao Family Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, Irvine

Must be taking: Temozolomide

Must not be taking: Antidepressants

Disqualifiers: Prior chemotherapy, Hypersensitivity, Pregnancy, 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

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

Compensation: Varies

Number of Visits: 3

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether mirtazapine, an antidepressant, can reduce depression, nausea, and vomiting, and help maintain weight in people with glioma (a type of brain tumor) undergoing Temozolomide (TMZ) therapy. Researchers aim to assess patients' tolerance to mirtazapine's side effects during the study. It suits individuals diagnosed with glioma who have not yet started TMZ treatment and have discontinued any antidepressant medications for at least a month. As a Phase 2 trial, this study measures mirtazapine's effectiveness in an initial, smaller group, offering participants a chance to contribute to important research.

Do I need to stop my current medications to join the trial?

Yes, you need to stop any anti-depressant medications at least a month before joining the trial.

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

Research shows that mirtazapine is generally well-tolerated by patients. Some studies have found that it not only helps with depression but also reduces nausea and vomiting. This can be particularly beneficial for people with brain tumors undergoing chemotherapy. Although data on using mirtazapine for cancer-related symptoms is limited, its approval for treating depression suggests it is safe to use. However, side effects can vary among individuals. Studies have not found any major changes in overall survival, indicating that mirtazapine does not seem to worsen the illness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about mirtazapine for brain tumors because, unlike typical treatments that focus solely on shrinking the tumor, mirtazapine may also address the side effects of depression, nausea, and vomiting that glioma patients often experience. Most brain tumor treatments, like Temozolomide, target the tumor directly, but mirtazapine works by modulating neurotransmitters in the brain, potentially improving mood and quality of life for patients. Additionally, this antidepressant could help with weight management, which is crucial for maintaining strength during cancer treatment.

What evidence suggests that mirtazapine might be an effective treatment for depression, nausea, and vomiting in glioma patients?

Research has shown that mirtazapine can help with depression, nausea, and vomiting, especially in cancer patients. It increases certain chemicals in the brain, lifting mood and easing nausea. Some studies suggest it can also help patients maintain their weight, which is often challenging during cancer treatment. This trial will assess mirtazapine's potential to help glioma patients with these symptoms. Overall, mirtazapine's effects on mood and appetite make it a promising option for managing these issues during cancer therapy. ^{1 2 4 6 7}

Who Is on the Research Team?

Daniela Bota, MD PHD

Principal Investigator

University of California, Irvine

Are You a Good Fit for This Trial?

This trial is for adults over 18 with high-grade glioma who are about to start Temozolomide therapy and have not used it before. They must be able to perform daily activities at a moderate level (KPS of at least 60), understand English, sign consent forms, agree to use contraception, and have stopped antidepressants for a month.

Inclusion Criteria

I will be treated with temozolomide as part of my cancer care.

Willing to use approved methods of contraception for duration of study

I stopped taking antidepressants at least a month ago.

Exclusion Criteria

I am allergic to Mirtazapine and certain nausea medications.

I have received chemotherapy for brain cancer before.

Your doctors think you may not live for more than three months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mirtazapine for eight weeks to assess changes in depression, nausea, vomiting, and weight

8 weeks

3 visits (baseline, 4 weeks, 8 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mirtazapine

Trial Overview

The study tests if Mirtazapine can help reduce depression, nausea, vomiting, and maintain weight in patients with brain tumors undergoing Temozolomide chemotherapy. It also checks how well patients tolerate the drug during treatment.

How Is the Trial Designed?

Group I: mirtazapine in glioma patients treated with Temozolomide Experimental Treatment 1 Intervention

Using the well-known Beck Depression Inventory, we will assess the changes in depression scores from baseline to after four and eight weeks of treatment with mirtazapine. We will also assess the change in nausea, vomiting, and weight at the same time points, and collect information on tolerability of mirtazapine throughout the course of the study.

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?

University of California, Irvine

Lead Sponsor

Trials

580

Recruited

4,943,000+

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]

Recent research has shown that certain psychiatric drugs, including valproic acid, fluoxetine, escitalopram, and aripiprazole, may have potential in treating malignant brain tumors, highlighting their anticancer properties through various laboratory and clinical studies.

The review emphasizes the need to address limitations in repurposing these medications for brain cancer treatment, particularly for vulnerable populations like children and pregnant women, while suggesting future research directions to improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surprising Anticancer Activities of Psychiatric Medications: Old Drugs Offer New Hope for Patients With Brain Cancer. Zhuo, C., Xun, Z., Hou, W., et al.[2020]

Psychotropic drugs, such as antipsychotics and antidepressants, can cross the blood-brain barrier and may inhibit the growth of glioma by affecting key signaling pathways involved in cell proliferation and apoptosis.

These drugs have shown potential as anticancer agents in preclinical and clinical studies, suggesting they can be repurposed for glioma treatment while maintaining their established safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug repositioning: Using psychotropic drugs for the treatment of glioma. You, F., Zhang, C., Liu, X., et al.[2022]

In a phase II study involving 30 patients with brain metastases from non-small cell lung cancer (NSCLC), temozolomide (TMZ) was found to be an active and safe treatment option, with 10% of patients achieving an objective response, including two complete remissions.

No severe (grade 3 or 4) toxicities were reported, and all treatment-related adverse events were mild to moderate, indicating that TMZ can be administered without significant safety concerns in this heavily pre-treated patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral temozolomide in heavily pre-treated brain metastases from non-small cell lung cancer: phase II study. Giorgio, CG., Giuffrida, D., Pappalardo, A., et al.[2018]

Temozolomide (TMZ) is commonly used as an adjuvant therapy for malignant glioma, but in this case study, a patient developed treatment-related acute myeloid leukemia (t-AML) after receiving 15 cycles of TMZ, highlighting a rare but serious complication.

The case raises questions about the duration of TMZ therapy, as the patient showed no tumor progression but still developed t-AML, suggesting a need for better guidelines to balance treatment benefits and risks in long-term TMZ use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case of Therapy-Related Acute Myeloid Leukemia Associated with Adjuvant Temozolomide Chemotherapy for Anaplastic Astrocytoma. Kosugi, K., Saito, K., Takahashi, W., et al.[2018]

A retrospective review of 33 isolated mirtazapine ingestions showed that overdoses are generally well tolerated, with the most common symptoms being drowsiness and lethargy, and no reported deaths.

Among the 23 patients with recorded symptoms, cardiovascular effects were noted in 4, including tachycardia in 3 patients, indicating that while mirtazapine overdoses can cause some cardiovascular symptoms, they are not severe in most cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes after isolated mirtazapine (Remeron) supratherapeutic ingestions. LoVecchio, F., Riley, B., Pizon, A., et al.[2022]

Cediranib, whether used alone or with lomustine, did not show improved efficacy compared to lomustine alone in treating recurrent glioblastoma, indicating limited effectiveness of this combination.

The addition of bevacizumab to radiation and temozolomide improved progression-free survival in newly diagnosed glioblastoma patients, but it did not extend overall survival, suggesting that while it may delay disease progression, it does not necessarily lead to longer life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

2010 Society for Neuro-Oncology Annual Meeting: a report of selected studies. Ahluwalia, MS.[2018]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12559032/

Survival outcomes associated with antidepressant use in ...

The median age at diagnosis was 62 (IQR 52–70) years with a median overall survival of 13.8 months. Of the cohort, 44% utilized antidepressants after diagnosis, ...

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pmc.ncbi.nlm.nih.gov

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

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Overall, the data was of poor quality, limited by small sample size and bias. However, mirtazapine showed effectiveness in treating depression, ...

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sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0014299919304911

Mirtazapine increases glial cell line-derived neurotrophic ...

Mirtazapine treatment significantly increased GDNF mRNA expression and GDNF release in both C6 cells and primary astrocytes.

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clinicaltrials.gov

clinicaltrials.gov/study/NCT03935685?term=AREA%5BBasicSearch%5D(remeron)&rank=2

Pilot Study of Mirtazapine for the Dual Tx of Depression ...

The purpose of the study is to estimate the ability of mirtazapine to reduce depression, nausea, and vomiting, and maintain weight in depressed glioma ...

5.

academic.oup.com

academic.oup.com/noa/article/7/1/vdaf075/8162438

The effect of antidepressants on glioblastoma survival

Despite improvements in care, it continues to carry a poor prognosis, with 5-year survival rates under 7% and an average survival time of 8 ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7516105/

Antidepressant drug use in glioblastoma patients

Nineteen patients (29.2%) were on antidepressant drugs at the time of their tumor diagnosis. No differences were observed in OS between those patients who had ...

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withpower.com

withpower.com/trial/phase-3-glioma-1-2019-4a1f7

Mirtazapine for Brain Tumor · Info for Participants

This trial is testing whether mirtazapine can help reduce depression, nausea, vomiting, and weight loss in brain tumor patients undergoing chemotherapy.