Clinical trial NCT04748523: Effect of Mirtazapine Versus Placebo in Patients With Non-small Cell Lung Cancer and Anorexia
Official title: Effect of Mirtazapine Versus Placebo on Appetite, Nutritional Status and Quality of Life in Non-small Cell Lung cáncer Patients With Anorexia; Randomized Double-blind Clinical Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Anorexia
Non-small Cell Lung Cancer
Lead sponsor: Instituto Nacional de Cancerologia de Mexico
Sponsor class: OTHER
First posted: 2021-02-10
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind clinical trial
Primary purpose: TREATMENT

Brief summary: The realization of this project will generate an important advance in knowledge regarding one of the most important comorbidities in cancer patients: malnutrition.

Currently, comprehensive treatments of cancer patients recognize the importance of the assessment of nutritional status, and the impact it has on the prognosis, quality of life and toxicity generated by cancer treatment. Due to this, it is imperative to offer diagnostic tools that identify patients in a timely manner and, in addition to this, offer therapeutic strategies for the improvement of nutritional status, in an adjuvant manner to their oncological treatment.

It is widely recognized that the cachexia-anorexia syndrome (CACS) is present in 30 to 80% of cases in cancer patients and this proportion increases as the disease progresses, with weight loss being a powerful predictor of shorter survival. Unfortunately, current therapies available to treat anorexia and / or cancer-associated cachexia offer only partial results, mainly because the intervention is late and the development of an earlier and more effective intervention is still sought. Mirtazapine has recently gained attention not only because of its antidepressant effect, but also because of its potential benefit in patients with anorexia and weight loss, recently reported in a phase II study. Therefore, it is important to continue its evaluation through a randomized, double-blind clinical trial in which the effect of mirtazapine is compared and it is determined if it is superior compared to placebo to increase appetite in patients with NSCLC who present with anorexia.

This type of strategy is a relevant therapeutic option in those patients in whom nutritional counseling by itself is not sufficient to counteract the damage caused by anorexia and to cope with or prevent the development of cachexia.

Detailed description: Lung cancer is the leading cause of cancer death in Mexico and the world. One of the comorbidities most commonly associated with this type of malignancy is malnutrition, which occurs in approximately 40-50% of newly diagnosed cases. In addition to its high incidence, malnutrition in patients with cancer is of great relevance due to the negative effect that this entails on the quality of life and the prognosis of patients, as well as the increase in toxicity associated with oncological treatment. Malnutrition is a pathological state in which the deficiency in the adequate contribution of energy contributes to its development, producing a systemic catabolic state; Its etiology is variable, however, in most patients malnutrition is associated with a lack of appetite, which is called anorexia.

Mirtazapine is a tetracyclic antidepressant which has been widely used for the treatment of depression. Several clinical studies have proven its efficacy in this indication, with more than 5000 patients endorsing its clinical effect compared to placebo, other tetracyclic antidepressants and trazodone. In addition to its effect on mood, it has been observed that mirtazapine, used in standard doses, induces weight gain, increasing appetite and food consumption compared to patients receiving placebo.

The increase in appetite with consequent weight gain and increased food intake may be due to the blocking of 5HT1b, 5-HT2, 5-HT3, H1 receptors, involved in the regulation of appetite. A pilot study of 2 doses of mirtazapine (15 or 30 mg per day) in ambulatory cancer patients with pain and other discomforts suggests that it provides a significant improvement in quality of life, particularly in weight and energy intake. Recently, another phase II study observed that 57% of oncology patients, ambulatory, non-depressed, increased their appetite and body weight when treated with mirtazapine for 4 weeks. Despite these encouraging data, the study included a small sample of patients, so it is not possible to generate robust conclusions from these data.

The objective of this protocol is to conduct a prospective, randomized, double-blind clinical trial to evaluate the effect of Mirtazapine on appetite, nutritional status and quality of life in patients with anorexia associated with lung cancer. The sample would include 86 patients, 43 patients with Mirtazapine and 43 sith placebo for 8 weeks, with an inducing dose of 15 mg to a máximum of 30 mg. The methodology for conducting this study consists of recruiting patients diagnosed with anorexia according to the anorexia-cachexia (ACS) scale, which has a cut-off point specifically validated for lung cáncer. Once the patient is selected, they are invited to participate in the study and an informed consent is requested. Subsequently a subjective global evaluation is performed, a 24-hour reminder of energy consumption, evaluation of anthropometric measures (weight, height,% weight loss, body mass index), evaluation of body composition (% fat, fat-free mass and phase angle), common gastrointestinal adverse effects of chemotherapy according to CTCAE, an evaluation of anxiety and depression (HADS) , as well as determination of quality of life through the questionnaire "The European organization for research and treatment of cancer quality of life questionnaire (QLQ) -C30 and (QLQ) LC-13", validated for Mexican population.

All determinations will be made at baseline, at 4 and at 8 weeks. All the variables are going to be evaluated inside each groups and between groups. It´s going to be considered significant p ≤ 0.05.

Eligibility criteria: Inclusion Criteria:

* Outpatients over 18 years of age who are receiving care in INCan with histopathological diagnosis of advanced stage non-small cell lung cancer (IIIB or IV).
* A score ≤ 32 on the cachexia anorexia scale or ≥ 5% weight loss in the last month.
* Good performance status (ECOG 0-2)
* That they are receiving chemotherapy as standard treatment or tyrosine kinase inhibitors or immunotherapy.
* Have a life expectancy\> 8 weeks.
* Accept and sign informed consent letter.

Exclusion Criteria:

* Known allergy to mirtazapine
* Patients who are treated with antidepressants
* Patients who are under treatment with megestrol acetate
* Patients with moderate hepatic and / or renal dysfunction (bilirubin level ≥ 1.5 x above normal limits (UNL), AST and ALT ≥ 5 x UNL, or creatinine ≥5 x UNL).
* Those unable to take medication orally.
* Patients with mechanical obstruction of the gastrointestinal tract, ascites or generalized edema.
* Patients with a history of phenylketonuria (preparation contains phenylalanine).
* Patients with delirium.

Primary outcomes:
measure: Percentage of patients with Anorexia
timeFrame: From the baseline assessment to 4 and 8 weeks
measure: Energy Consumption
timeFrame: From the baseline assessment to 4 and 8 weeks
Secondary outcomes:
measure: Weight
timeFrame: From the baseline assessment to 8 weeks
measure: Body Mass Index
timeFrame: From the baseline assessment to 8 weeks
measure: Subjetive Global Assessment
timeFrame: From the baseline assessment to 8 weeks
measure: Protein consumption
timeFrame: From the baseline assessment to 8 weeks
measure: Lipids consumption
timeFrame: From the baseline assessment to 8 weeks
measure: Carbohydrates consumption
timeFrame: From the baseline assessment to 8 weeks
measure: Body fat
timeFrame: From the baseline assessment to 8 weeks
measure: Fat free mass
timeFrame: From the baseline assessment to 8 weeks
measure: phase angle
timeFrame: From the baseline assessment to 8 weeks
measure: Quality of life - Global status
timeFrame: From the baseline assessment to 8 weeks
measure: Quality of life - physical functioning
timeFrame: From the baseline assessment to 8 weeks
measure: Quality of life -Role functioning
timeFrame: From the baseline assessment to 8 weeks
measure: Quality of life - Emotional functioning
timeFrame: From the baseline assessment to 8 weeks
measure: Quality of life - Cognitive functioning
timeFrame: From the baseline assessment to 8 weeks
measure: Quality of life - Social functioning
timeFrame: From the baseline assessment to 8 weeks
measure: Quality of life - Fatigue
timeFrame: From the baseline assessment to 8 weeks
measure: Quality of life - Nausea and vomiting
timeFrame: From the baseline assessment to 8 weeks
measure: Quality of life - loss of appetite
timeFrame: From the baseline assessment to 8 weeks
measure: Anxiety
timeFrame: From the baseline assessment to 8 weeks
measure: Depression
timeFrame: From the baseline assessment to 8 weeks
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: Instituto Nacional de Cancerologia
Study officials:
affiliation: Instituto Nacional de Cancerología de México
name: Oscar G Arrieta Rodriguez, M.D., M.Sc.
role: PRINCIPAL_INVESTIGATOR
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