Anorexia is common symptom in cancer patients and is associated with increased morbidity
and mortality. However timely detection with objective tools is necessary to establish
the diagnosis of anorexia and to assess the magnitude of change over time. The anorexia
pathophysiology is not clearly understood and treatment options are limited. Anecdotal
historical benefits of smoking marijuana on nausea, pain and anorexia led to studies with
marijuana and synthetic cannabinoids from Δ-9-tetrahydrocannabinol, the main active agent
in marijuana. The endogenous cannabinoid system with its receptors CB1 and CB2 regulate
appetite in four functional levels: (1) limbic system (hedonistic quality), (2)
hypothalamus (appetite stimulant), (3) intestinal, and (4) tissue adipose.

Nabilone, a synthetic analogue of THC approved in Mexico for nausea and vomiting induced
by chemotherapy is also used in palliative care units for clinical improvement in
increased appetite patients in terminal stages, however, there are no clinical trials
demonstrating this benefit.

Nabilone Effect on the Attenuation of Anorexia, Nutritional Status and Quality of Life in Lung Cancer Patients

Non-Small Cell Lung Cancer

Anorexia

Cachexia

Weight Lose

Background: Lung cancer is the leading cause of cancer death in Mexico and the world.
Malnutrition is often associated with this type of cancer appearing in about 40-50% of
patients the diagnosis made, affecting the quality of life and prognosis, as well as
increased toxicity to cancer treatment. Cancer anorexia is characterized by loss of
appetite and is the main cause of reduced food consumption in lung cancer patients.
Anorexia occurs in up to 25% of cases. Unfortunately, current therapies available to
treat anorexia and / or cachexia associated with cancer provide only partial results,
mainly because the intervention is delayed and the development of an early and effective
intervention is still looking.

In most patients, malnutrition is associated with a hyporexia secondary to the production
of pro-inflammatory cytokines such as tumor necrosis factor (TNF), leading to an increase
in metabolism and appetite loss. Nabilone is a synthetic cannabinoid derivative that is
widely used in oncology for its antiemetic and adjuvant effect of pain. Although widely
used for the treatment of anorexia in palliative care, no randomized clinical trials
demonstrating an effect on cancer-associated anorexia, however, in animal models,
stimulation of cannabinoid receptors, mainly through CB1 receptor can modulate
hypothalamic circuits in the brain stem, which in turn regulate food intake and satiety.
Moreover cannabinoids are able to block the effects of TNF in the nervous system, which
is associated with appetite changes in cancer patients. Additionally, agonists of
cannabinoid receptors attenuated weight loss in murine models of anorexia.

Additionally, to diagnosis anorexia The Anorexia-Cachexia scale (A/CS-12) from The
Functional Assessment of Anorexia-Cachexia therapy (FAACT) questionnaire relates
differences in symptoms and severity, assigning a value of 0-4 for each of 12 items. A
2010 consensus of special interest group of CACS from ESPEN (The European Society for
Clinical Nutrition and Metabolism) in order to unify criteria, proposed that a score ≤24
of the A/CS-12 would be enough to establish a diagnosis of anorexia.

The administration of Nabilone in patients with anorexia associated with Non-Small Cell
Lung Cancer (NSCLC) is expected to increase appetite, nutritional status and quality of
life.

Methods: randomized double-blind clinical trial assessing Nabilone effect in non-small
cell lung cancer (NSCLC) patients with unresectable stage III/IV NSCLC, ECOG performance
status (ECOG PS) 1-2 and anorexia (main criteria: score of Anorexia Cachexia scale
(AC/S-12) from Functional Assessment of Anorexia Cachexia Therapy ≤24). Patients are
randomized to Nabilone at 0.5mg to 1mg, or placebo, given daily orally for 8 weeks.
Changes are evaluated from baseline to week 2, 4, and 8.

Time Assessment Dose T0 Baseline 0.5mg T1 2 weeks 1 mg T2 4 weeks 1 mg T3 8 weeks 1 mg

Sample size:

To determine the sample size is considered the effect of cannabinoid (dronabinol, 2.5 mg
/ 22 days) in appetite in cancer patients by a difference in proportions of 34% more than
placebo, requiring 32 patients per group plus 20% of loss gives us a total of 39 patients
per group, with a power of 90% and an α of 0.05

Nabilone

Placebo

Nabilone Effect on the Attenuation of Anorexia, Nutritional Status and Quality of Life in Patients With Anorexia Associated With Advanced Lung Cancer: Randomized Double Blind Clinical Trial

Lack of desire to eat food. Will be obtained through a questionnaire Anorexia / Cachexia
scale from Functional Assessment of Anorexia Cachexia Therapy (FAACT) (score ≤24
diagnosis of anorexia)

It is an index of a person's weight in relation to height

convenient, fast and cheaper method used to make a nutritional assessment, consisting of
3 parts: anamnesis, physical examination and qualification.

Total calories consumed on average per day for a subject

MD M Sc

Total protein grams consumed on average per day for a subject

Total lipids grams consumed on average per day for a subject

Total carbohydrate grams consumed on average per day for a subject

adverse effect from Common terminology criteria for adverse event

The Global status of Quality of Life evaluation is evaluated using the validated
Mexican-Spanish version of the European Organization for the Research and Treatment of
Cancer Quality of Life Questionnaires specific for cancer with the items 29 and 30.

The Physical functioning evaluation is evaluated from the validated Mexican-Spanish
version of the European Organization for the Research and Treatment of Cancer Quality of
Life Questionnaires specific for cancer

The Role functioning evaluation is evaluated from the validated Mexican-Spanish version
of the European Organization for the Research and Treatment of Cancer Quality of Life
Questionnaires specific for cancer

The Emotional Functioning evaluation is evaluated from the validated Mexican-Spanish
version of the European Organization for the Research and Treatment of Cancer Quality of
Life Questionnaires specific for cancer

The Social Functioning evaluation is evaluated from the validated Mexican-Spanish version
of the European Organization for the Research and Treatment of Cancer Quality of Life
Questionnaires specific for cancer

The Nausea/Vomiting evaluation is evaluated from the validated Mexican-Spanish version of
the European Organization for the Research and Treatment of Cancer Quality of Life
Questionnaires specific for cancer

The Fatigue evaluation is evaluated from the validated Mexican-Spanish version of the
European Organization for the Research and Treatment of Cancer Quality of Life
Questionnaires specific for cancer

The appetite loss evaluation is evaluated from the validated Mexican-Spanish version of
the European Organization for the Research and Treatment of Cancer Quality of Life
Questionnaires specific for cancer

Patients start receiving a dose of 0.5 mg daily oral nabilone the first 2 weeks and then
1 mg to complete 8 weeks.

Patients start receiving a dose of 0.5 mg daily oral placebo the first 2 weeks and then 1
mg to complete 8 weeks.

Nabilone Effect on the Attenuation of Anorexia, Nutritional Status and Quality of Life in Lung Cancer Patients

About this trial

Study ID

Status

Type

Phase

Placebo

Accepting

Not accepting

Trial Timing

What is this trial about?

What are the participation requirements?

Locations

Location

Status