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

120 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing whether mirtazapine can help reduce depression, nausea, vomiting, and weight loss in brain tumor patients undergoing chemotherapy. The study will monitor these patients over a period of time to see if their symptoms improve and if the medication is well-tolerated. Mirtazapine has been used to prevent chemotherapy-induced nausea and vomiting (CINV) and improve quality of life in cancer patients.

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.

What evidence supports the effectiveness of the drug Mirtazapine for brain tumors?

Some psychiatric drugs, like antidepressants, have shown potential in treating brain tumors by affecting brain chemicals and making cancer cells more sensitive to other treatments. This suggests that drugs like Mirtazapine, which is an antidepressant, might also have similar effects. ^{1 2 3 4 5}

Is mirtazapine generally safe for humans?

Mirtazapine is generally well-tolerated in humans, with common side effects being drowsiness and weight gain. In cases of overdose, symptoms like drowsiness and mild heart rate changes were observed, but no deaths occurred, indicating it is generally safe. ^{6 7 8 9 10}

How is the drug Mirtazapine unique for treating brain tumors?

Mirtazapine is unique for brain tumors as it is primarily an antidepressant, unlike standard chemotherapy drugs like temozolomide, which are typically used for brain tumors. This suggests a novel approach, potentially targeting different pathways or symptoms associated with brain tumors. ^{11 12 13 14 15}

Research Team

Daniela Bota, MD PHD

Principal Investigator

University of California, Irvine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Brexpiprazole, a Serotonin-Dopamine Activity Modulator, Can Sensitize Glioma Stem Cells to Osimertinib, a Third-Generation EGFR-TKI, via Survivin Reduction. [2020]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Surprising Anticancer Activities of Psychiatric Medications: Old Drugs Offer New Hope for Patients With Brain Cancer. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Seizures in low- and high-grade gliomas: current management and future outlook. [2010]

4. Ireland pubmed.ncbi.nlm.nih.gov

Drug repositioning: Using psychotropic drugs for the treatment of glioma. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

How about Levetiracetam in Glioblastoma? An Institutional Experience and Meta-Analysis. [2021]

6. England pubmed.ncbi.nlm.nih.gov

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

7. United States pubmed.ncbi.nlm.nih.gov

Outcomes after isolated mirtazapine (Remeron) supratherapeutic ingestions. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Mirtazapine, a dopamine receptor inhibitor, as a secondary prophylactic for delayed nausea and vomiting following highly emetogenic chemotherapy: an open label, randomized, multicenter phase III trial. [2021]

9. Greece pubmed.ncbi.nlm.nih.gov

Effect of Mirtazapine for the Prevention of Nausea and Vomiting in Patients With Thoracic Cancer Receiving Platinum-based Chemotherapy. [2023]

10. Japan pubmed.ncbi.nlm.nih.gov

[Efficacy of mirtazapine for appetite loss and nausea of the cancer patient--from clinical experience in Memorial Sloan-Kettering Cancer Center]. [2018]

11. Ireland pubmed.ncbi.nlm.nih.gov

Oral temozolomide in heavily pre-treated brain metastases from non-small cell lung cancer: phase II study. [2018]

12. United States pubmed.ncbi.nlm.nih.gov

A Case of Therapy-Related Acute Myeloid Leukemia Associated with Adjuvant Temozolomide Chemotherapy for Anaplastic Astrocytoma. [2018]

13. England pubmed.ncbi.nlm.nih.gov

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

14. United States pubmed.ncbi.nlm.nih.gov

Alternative chemotherapeutic agents: nitrosoureas, cisplatin, irinotecan. [2018]

15. United States pubmed.ncbi.nlm.nih.gov

A phase II study of the farnesyl transferase inhibitor, tipifarnib, in children with recurrent or progressive high-grade glioma, medulloblastoma/primitive neuroectodermal tumor, or brainstem glioma: a Children's Oncology Group study. [2016]