Efficacy and Safety Analyses of Mirtazapine in NSCLC Patients With Depression

January 6, 2016 updated by: Li Zhang, Sun Yat-sen University

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

236

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • GuangZhou, Guangdong, China, 510060
        • Cancer Center of Sun-Yat Sen University (CCSYSU)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: mirtazapine
Mirtazapine arm will be orally administered with mirtazapine 15mg, QD, consecutive medication for 8 weeks; along with palliative chemotherapy regimen decided by investigators.
Drug: Mirtazapine
Patients in mirtazapine arm will be orally administered mirtazapine as an anti-depression therapy; along with palliative chemotherapy.
Other Names:
  • Treatment arm: mirtazapine administration
Placebo Comparator: Placebo
Placebo arm will be orally administered with placebo 15mg, QD, consecutive medication for 8 weeks; along with palliative chemotherapy regimen decided by investigators.
Drug: Placebo
Patients in placebo arm will be orally administered placebo; along with palliative chemotherapy.
Other Names:
  • Comparative arm: placebo administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants responded to treatment.
Time Frame: baseline, and 3 weeks (d22), and 8 weeks (d57), and follow-up (d71, d85)
Using PHQ-9 or HAMD-17 questionnaire to assess the change of depression scores at the time points above. The measure unit is questionnaire score point, remain the same at every time points. And to calculate response number of patients (patients had 50% percent of depression questionnaire score points reduction compared to baseline after treatment initiation) and recovery number of patients (patients had PHQ-9 score less than 8 points PHQ-9 score less than 8 points during the treatment).
baseline, and 3 weeks (d22), and 8 weeks (d57), and follow-up (d71, d85)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response duration
Time Frame: From date of randomization until the date of first documented regression recurrence, assessed up to 12 weeks"
Regression recurrence defined as PHQ-9 score ascending above baseline level.
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
Time Frame: baseline, and 3 weeks (d22), and 8 weeks (d57), and follow-up (d71, d85)
Using EORTC QLQ-C30 (V3.0) to assess the quality of life change at the time points above. The measure unit is questionnaire score point, remain the same at every time points. And to calculate improved number of patients (patients had quality of life questionnaire score points gained compared to baseline after treatment initiation)
baseline, and 3 weeks (d22), and 8 weeks (d57), and follow-up (d71, d85)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2015

Primary Completion (Anticipated)

June 1, 2018

Study Completion (Anticipated)

June 1, 2019

Study Registration Dates

First Submitted

December 11, 2015

First Submitted That Met QC Criteria

January 6, 2016

First Posted (Estimate)

January 8, 2016

Study Record Updates

Last Update Posted (Estimate)

January 8, 2016

Last Update Submitted That Met QC Criteria

January 6, 2016

Last Verified

January 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MDES20150107

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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