Clinical trial NCT03283488: Comparison Between Mirtazapine and Megestrol for the Control of Anorexia-cachexia in Cancer Patients in Palliative Care.
Official title: Randomized, Double-blind Clinical Trial of the Use of Mirtazapine Versus Megestrol for the Control of Anorexia-cachexia in Cancer Patients in Palliative Care.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cachexia; Cancer
Anorexia
Keywords: anorexia
cachexia
mirtazapine
megestrol
palliative care
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
First posted: 2017-09-14
Enrollment: 52
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Cancer-associated anorexia-cachexia is an insidious syndrome that has a major impact on the patient's quality of life, but is also associated with a significant reduction in survival. Despite its clinical importance, it remains a widely underestimated and untreated condition. Considering the scarcity of pharmacological measures, it is necessary to invest in studies that may contribute to the rational and effective treatment of this clinical condition. Mirtazapine has a special therapeutic potential because it is a well-tolerated drug with few adverse effects and with well-known orexigenic action in clinical practice.The objective of this study is to evaluate the effect of mirtazapine as a pharmacological measure in the management of cancer-related anorexia-cachexia in patients in palliative care. A randomized, double-blind clinical trial involving 52 cancer patients with anorexia-cachexia in palliative care will be conducted. Patients will be randomized to receive mirtazapine or megestrol and will be evaluated longitudinally for a period of 8 weeks. The primary endpoint will be to assess the effect of mirtazapine on anorexia and weight gain and secondary outcomes will be to assess the tolerability and safety of mirtazapine and the effect of mirtazapine on body composition, quality of life, and functional capacity of patients.

Detailed description: Cancer-associated anorexia-cachexia is an insidious syndrome that has a major impact on the patient's quality of life, but is also associated with a significant reduction in survival. Unintentional weight loss can predict a poor prognosis in cancer patients which is most likely due to decreased doses of treatment. Despite its clinical importance, it remains a widely underestimated and untreated condition. Considering the scarcity of pharmacological measures, it is necessary to invest in studies that may contribute to the rational and effective treatment of this clinical condition. Mirtazapine has a special therapeutic potential because it is a well-tolerated drug with few adverse effects and with well-known orexigenic action in clinical practice. It has been shown to have side effects of increased appetite and weight gain in cancer subjects with depression and nausea, as well as in non-depressed cancer patients, but there are not, as yet, randomized controlled trials showing its effect on cancer-associated anorexia-cachexia. The objective of this study is to evaluate the effect of mirtazapine as a pharmacological measure in the management of cancer-related anorexia-cachexia in patients in palliative care. A randomized, double-blind clinical trial involving 52 cancer patients with anorexia-cachexia in palliative care will be conducted. Patients will be randomized to receive mirtazapine or megestrol and will be evaluated longitudinally for a period of 8 weeks. After the initial evaluation and randomization, patients will be reassessed after 4 and 8 weeks at an outpatient clinic where they will be evaluated for the following variables: (1) General and demographic characteristics; (2) Usual food intake; (3) Anthropometric evaluation; (4) Presence and degree of symptoms using the Edmonton Symptom Assessment System; (4) Status performance using the Karnofsky performance status; (5) Quality of life using the QLQ-C30 Questionnaire; (6) Depression using the Hospital Anxiety and Depression Scale; (7) Prognosis using the Palliative Prognostic Score; (8) Evaluation of functional capacity using hand grip strength and gait speed; (9) Body composition using electrical bioimpedance and dual energy x-ray absorptiometry; (10) Physical Activity Behaviour using a tri-axial accelerometer. Patients will also be contacted via telephone calls at weeks 1, 2, 3, 5 and 6 for information regarding adverse events and drug compliance. The questioning about the occurrence of adverse events will also be performed at the outpatient clinic. Self-report of ingestion of tablets and counting of tablets on return of packages at the end of the study will be used to determine patient compliance. It is expect that use of mirtazapine can bring benefits increasing appetite and the body weight in cancer patientes in palliative care compared to the use of megestrol.

Eligibility criteria: Inclusion Criteria:

* Patients aged ≥ 50 years.
* Patients with confirmed diagnosis of cancer by histopathological examination, including those not yet submitted to any therapy because they are in the therapeutic definition phase and those whose therapies have already been suspended because they are ineffective.
* Patients with cancer progression, with either local or distant metastases, documented by radiological or histopathological methods.
* Patients complaining of anorexia graded by the patient as ≥ 5 by the Edmonton Sympton Assessement Scale.
* Patients with weight loss ≥ 2% in the last 2 months or weight loss ≥ 5% in the last 6 months, referred by the patient or documented in electronic medical records, compared to the stable weight before diagnosis.
* Patients with a life expectancy of ≥ 2 months by the Palliative Prognostic Score.
* Patients with performance status greater than or equal to 60% using the Karnofsky Performance Status scale.

Exclusion Criteria:

* Patients diagnosed with depression or using antidepressant therapy with a score ≥ 12 in the depression items of the Hospital Anxiety and Depression Scale.
* Patients with unstable doses of corticosteroids.
* Patients with moderate renal and/or hepatic dysfunction (total bilirubin ≥ 1.5x the upper limit of normal, AST and ALT ≥ 5x upper limit of normal or creatinine ≥1.5x upper limit of normal).
* Patients with Central Nervous System metastases.
* Patients with inability to take oral medications.
* Patients with mechanical obstruction of the gastrointestinal tract.
* Patients with clinically bulky ascites and generalized edema.
* Patients with reports of allergy to the medications studied.
* Patients with hypothyroidism with TSH levels greater than or equal to 5 μU/mL and free T4 less than 0.7 ng/dL.
* Patients with uncorrected hydroelectrolytic disturbances, with altered serum sodium, potassium and/ or ionic calcium.
* Patients with persistent and uncontrolled nausea and/or vomiting associated with gastrointestinal tract neoplasia and/or chemotherapeutic or radiotherapeutic treatment.
* Patients with pacemakers.

Primary outcomes:
measure: Change in appetite
timeFrame: 8 weeks
measure: Change in body weight
timeFrame: 8 weeks
Secondary outcomes:
measure: Change in body lean and fat mass
timeFrame: 8 weeks
measure: Change in Quality of life
timeFrame: 8 weeks
measure: Assessment of muscle strength
timeFrame: 8 weeks
measure: Assessment of gait speed
timeFrame: 8 weeks
measure: Physical Activity behaviour
timeFrame: 8 weeks
measure: Incidence of treatment-related Adverse Events
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Ribeirão Preto
country: Brazil
facility: Clinics Hospital, Ribeirão Preto Medical School, University of São Paulo
state: São Paulo
Study officials:
affiliation: University of Sao Paulo
name: Nereida KC Lima, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Riechelmann RP, Burman D, Tannock IF, Rodin G, Zimmermann C. Phase II trial of mirtazapine for cancer-related cachexia and anorexia. Am J Hosp Palliat Care. 2010 Mar;27(2):106-10. doi: 10.1177/1049909109345685. Epub 2009 Sep 23.
citation: Theobald DE, Kirsh KL, Holtsclaw E, Donaghy K, Passik SD. An open-label, crossover trial of mirtazapine (15 and 30 mg) in cancer patients with pain and other distressing symptoms. J Pain Symptom Manage. 2002 May;23(5):442-7. doi: 10.1016/s0885-3924(02)00381-0.
citation: Tomiska M, Tomiskova M, Salajka F, Adam Z, Vorlicek J. Palliative treatment of cancer anorexia with oral suspension of megestrol acetate. Neoplasma. 2003;50(3):227-33.
citation: Wen HS, Li X, Cao YZ, Zhang CC, Yang F, Shi YM, Peng LM. Clinical studies on the treatment of cancer cachexia with megestrol acetate plus thalidomide. Chemotherapy. 2012;58(6):461-7. doi: 10.1159/000346446. Epub 2013 Feb 7.