Mirtazapine for Treatment of Cancer Associated Anorexia-cachexia

NCT03254173 | Completed Phase 2 DMC

• 1 other identifier: MCACS100
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

A randomized controlled clinical trial will be conducted to assess the efficacy of the FDA approved drug , mirtazapine , in treatment of cancer associated anorexia cachexia syndrome. Two arms will be compared . Arm A will involve 50 patients with confirmed advanced cancer receiving mirtazapine 15 mg once daily for 8 weeks \& Arm B will involve another 50 patients with confirmed advanced cancer receiving placebo for 8 weeks. Both arms will be compared to assess efficacy of mirtazapine in appetite stimulation primarily and to assess other outcomes secondarily which will be discussed later in details.

Conditions

Advanced Cancer; Cancer Associated Anorexia - Cachexia

Keywords

Mirtazapine; Anorexia - Cachexia; Advanced Cancer; Appetite

Outcome Measures

Primary Outcomes (1)

• Efficacy of mirtazapine in appetite stimulation in patients with cachexia due to advanced cancer with a change of increase of 1.5 degree on a numerical scale of 0 -10 as a target .

  Efficacy of mirtazapine in appetite stimulation in patients with cachexia due to advanced cancer with a change of increase 1.5 degree on a scale of 0-10 as a target , where 0 represents minimum appetite and 10 represents maximum appetite.

  It will be assessed at week 4 of receiving the intervention. The 4-week duration of treatment is of sufficient length to obtain benefit from an effective intervention for appetite.

Secondary Outcomes (5)

• Efficacy of mirtazapine in weight gain. ''Improved'' weight will be defined as a gain of ≥ 1 kg and ''maintained weight'' will be defined as a loss of <500 g, or a gain of <1 kg.

  It will be assessed at week 8 of receiving the intervention.

• Effect of mirtazapine in improving other symptoms , such as : nausea , vomiting , sleep with a change of decrease of ≥ 2 points on the ESAS ( Edmonton Symptom Assessment Scale ) from baseline.

  It will be assessed at week 8 of receiving the intervention.

• Effect of mirtazapine in improving quality of life : will be measured by an increase of 16 points in the FAACT questionnaire ( Functional Assessment of Anorexia\Cachexia Therapy ) with anorexia \ cachexia subscale .

  It will be assessed at week 8 of receiving the intervention.

• Changes in inflammatory cytokines associated with mirtazapine administration : quantitative c-reactive protein (CRP) , IL-6, and YKL-40 serum levels .

  It will be assessed at week 8 of receiving the intervention.

• Safety of mirtazapine use : Toxicity will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0

  It will be assessed at baseline , then at 14-day intervals until day 28 and after 30 days from the date of the last dose of the study drug.

Study Arms (2)

Arm A

ACTIVE COMPARATOR

Mirtazapine 30 mg oral tablets ( Remeron 30 mg oral tablets ) , as half tablet daily , i.e , 15mg daily , before sleep for a duration of 8 weeks

Drug: Mirtazapine 30 mg oral tablets

Arm B

PLACEBO COMPARATOR

Placebo oral tablets , as half tablet daily before sleep for a duration of 8 weeks

Drug: Placebo oral tablets

Interventions

Mirtazapine 30 mg oral tablets DRUG

Mirtazapine 30 mg oral tablets ( Remeron 30 mg oral tablets) , half tablet before sleep for 8 weeks

Also known as: Remeron 30 mg oral tablets

Arm A

Placebo oral tablets DRUG

Placebo oral tablets , half tablet daily before sleep for 8 weeks

Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with confirmed advanced cancer.
• Patients with appetite score equal or more than 4 on a 0 to 10 scale (10 \_ worst appetite).
• Patients with weight loss more than 5 % of body weight over 6 months . Or : Patients with any degree of weight loss more than 2 % associated with BMI ( body mass index ) of less than 20.
• Patients able to take pills orally and not dependent on tube feeding (no oral mucosal inflammation interfering with oral intake or dysphagia as determined by clinical examination).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Normal organ function (creatinine ≤2× upper limit of normal, bilirubin ≤2; upper limit of normal).
• Ability to understand and willingness to sign written informed consent.
• Patients could be receiving concurrent chemotherapy or radiation therapy.
• Patients with an expected life span of at least 3 months.

You may not qualify if:

• Patients with weight gain for known cause , e.g. , ascites.
• Premenopausal women with childbearing potential with a positive pregnancy test.
• Patients unable to maintain oral intake .
• Patients with dementia or delirium.
• Patients with uncontrolled symptoms that could impact appetite or caloric intake such as nausea, pain, or depression will be excluded until their symptoms had stabilized for at least 2 weeks.
• Because improvement in anorexia and/or weight in depressed individuals could be due to an antidepressant effect of mirtazapine, rather than to a direct effect on anorexia, patients with moderate to severe depressive symptoms will be also excluded. the screening instrument will be a single-item interview assessing depressed mood of the Schedule for Affective Disorders and Schizophrenia (SADS) instrument which is validated and highly accurate in screening for depression when compared to the gold standard of semistructured diagnostic interviews, and is rated on a 6-point Likert scale, where 0 = no depression and 6 = extreme feelings of depression. Patients with a score of 4 or more will be excluded from the study as they are considered to be at high risk for depression.
• No treatment with antipsychotic agents such as risperidone, quetiapine, clozapine, phenothiazine, or butyrophenone for 30 days prior to or during protocol therapy.
• Patients with untreated vitamin B12 deficiency or endocrine abnormalities that could affect appetite, such as thyroid dysfunction and hypoadrenalism.
• Patients on supplements or medications with potential appetite-stimulating activity, such as megestrol acetate, corticosteroids, or thalidomide, will be excluded unless they are put on a stable dose for more than 2 weeks and continue to experience poor appetite.

Sponsors & Collaborators

• Catherine Naseef Hunter: lead

Study Sites (1)

Kasr Al Ainy - Cairo University - Faculty of Medicine

Cairo, 11956, Egypt

Location

MeSH Terms

Interventions

Mirtazapine

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Catherine N Hunter, Ass. lecturer

  Clinical Oncology Department at Kasr Al Ainy NEMROCK

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: * Treatment allocation will be concealed from patients, investigators, and study coordinators enrolling the participants. * The pills used in the study ( either remeron or placebo ) will be kept into opaque containers , in order to be concealed from patients , investigators and study coordinators.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assisstant Lecturer at clinical oncology department at Kasr Al Ainy NEMROCK

Model Details: double-blinded randomized controlled trial.

Study Record Dates

• First Submitted: June 11, 2017
• First Posted: August 18, 2017
• Study Start: March 26, 2018
• Primary Completion: October 17, 2019
• Study Completion: October 17, 2019
• Last Updated: February 5, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will share

Locations

EG (1)