Efficacy and Safety Analyses of Mirtazapine in NSCLC Patients With Depression

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. Eligible advanced NSCLC Patients with PHQ-9 score ≥ 8, and undertaking palliative chemotherapy will be enrolled into this study. patients will be stratified (gender, age, Numerical Rating Scale 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, Patient health questionnaire (PHQ-9), Hamilton Depression Scale (HAMD-17) and European Organization for Research on Treatment of Cancer (EORTC) quality of life questionnaire-C30 (QLQ-C30) questionnaires will be collected at baseline, 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). 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.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Pathology confirmed non-small cell lung cancer, undertaking palliative chemotherapy
* Age above 18 years old
* PHQ-9 score ≥ 8 points at baseline assessment
* Eastern Cooperative Oncology Group (ECOG) performance score 0 -2
* Orally administration of drugs without difficulties
* Eligible bone marrow function, liver and kidney function for chemotherapy
* Pregnancy test negative in 7 days for women of child-bearing age; willing to take contraception measures.
* Signed Informed consent form (ICF)

Exclusion Criteria:

* Clinical diagnosis of depression before advanced NSCLC confirmed
* Suicide tendency or behavior
* Mania in past medical history
* Received surgery or radiation therapy in 4 weeks
* Central nervous system (CNS) metastasis or spinal compression; except no symptoms and with no cortical hormonotherapy in 4 weeks.
* Systemically treatment with psychotropic medications, antihistamines drugs, antibiotics, cortical hormone therapy, antiepileptic drugs, immunosuppressive agents or other drugs might affect treatment in 4 weeks; or locally used of these drug in 2 weeks.
* AST or ALT ≥ 2.5 ULN without liver metastasis; or ≥ 5 ULN with liver metastasis.
* Serum creatinine ≥ 2 mg/dl
* Residual toxicity event ≥ CTCAE grade 2, except peripheral neurotoxicities.
* Any severe or uncontrolled systemic diseases judged by investigators.
* Any contraindication of mirtazapine.

Exclusion Criteria:

* Invalid subject after randomization
* Major protocol violations judged by investigators.
* Poor compliance
* Intolerable adverse events
* Subject withdraw ICF
* Any pregnancy events
* No clinical benefits due to clinical adverse events, laboratory abnormalities or other medical conditions
* Other reasons of treatment discontinuation judged by investigators.

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