Efficacy and Safety Analyses of Mirtazapine in the Treatment of Malignant Tumor Related Depression: A Phase II, Placebo-controlled, Randomized, Double-blinded Clinical Trial in Advanced Non-small Cell Lung Cancer Patients

Brief Summary

Detailed Description

Major depression prevail in patients with malignant tumor with an incident rate of 20% - 40%, 2-3 times more than the prevalence of population, especially high in patients with advanced solid tumor patients as 40% - 50.6%. National Comprehensive Cancer Network (NCCN) palliative care guideline recommended PHQ-9 as the diagnosis tool for depression, total scores ≥ 8 was considered the standard of malignant tumor related depression. Major depression had been proved related with malignant tumors, mirtazapine is the currently effective drug in anti-depression clinical therapy, have better tolerance and equal effect compared to Tricyclic antidepressants (TCAs) and 5-hydroxytryptamine (5-HT) or noradrenaline serotonin-norepinephrine reuptake inhibitors (NE-SNRIs). This is a phase II, placebo-controlled, randomized, double-blinded clinical trial. Study objective is to assess the efficacy and safety of mirtazapine in advanced NSCLC patients with malignant tumor related depression. Study hypothesis is that advanced NSCLC diagnosed with depression undertaking palliative chemotherapy with mirtazapine treatment for 8 weeks will have remarkable improvement in depression compared to baseline. Palliative chemotherapy and mirtazapine have better efficacy, recovery rate, response duration, tolerance and quality of life improvement than palliative chemotherapy and placebo. Moreover, mirtazapine could improve patients' anxiety and chemotherapy related nausea and vomit. Eligible advanced NSCLC Patients with PHQ-9 score ≥ 8, and undertaking palliative chemotherapy will be enrolled into this study. After baseline assessment (PHQ-9, HAMD-17 and EORTC QLQ-C30 questionnaires), 236 patients will be stratified (gender, age, NRS score for cancer pain 0-3/4-6/7-10) randomized (1:1) into mirtazapine or placebo treatment. Patients in mirtazapine arm will be orally administered with mirtazapine 15mg, QD, consecutive medication for 8 weeks; along with palliative chemotherapy regimen decided by investigators. Patients in placebo arm will be orally administered with placebo 15mg, QD, consecutive medication for 8 weeks; along with palliative chemotherapy regimen decided by investigators. During the treatment, PHQ-9, HAMD-17 and EORTC QLQ-C30 questionnaires will be collected at 3 weeks (d22) and 8 weeks (d57), or treatment discontinuation date due to depression deteriorated or suicidal tendency and behavior. Follow-up will last up to 4 weeks after treatment end with depression assessment (questionnaires every 2 weeks). If anti-depression therapy is not effective after 8 weeks treatment or treatment discontinuation, patients will be unblinded and receive other treatment according to investigators. Treatment end at 8 weeks. Study endpoints: primary endpoint is the anti-depression efficacy (response rate). Response defined as the PHQ-9 or HAMD-17 questionnaire score decrease ≥ 50% compared with baseline level. Secondary endpoints included: 1.recovery rate, recovery defined as the PHQ-9 score less than 8 points. 2. Response duration, defined as the time period from treatment response to regression recurrence (PHQ-9 score ascending above baseline level). 3. Quality of life improvement, define as the best quality of life score minus baseline level. 4. Compliance to anti-depression therapy, defined as the medication count at each follow-up time points.

Primary Outcomes

Secondary Outcomes

• Response duration(From date of randomization until the date of first documented regression recurrence, assessed up to 12 weeks")
• Number of participants had quality of life improvement(baseline, and 3 weeks (d22), and 8 weeks (d57), and follow-up (d71, d85))