Effect of Omega-3 Supplements on the Prevention of Cachexia in Head and Neck Cancer Treated With Radio(Chemo)Therapy

Study Overview
=================
Brief Summary
-----------------
Cancer cachexia is a complex metabolic process affecting up to 80% of patients suffering from an advanced-stage cancer. Moreover, 20 to 40% of all cancer deaths are caused directly by cachexia. Head and neck (H&N) cancer patients are nutritionally vulnerable since tumour localisation can interfere with food intake, since alcohol and tobacco abuse - two etiological risk factors of H&N cancer - are associated with nutritional deficits, and since the intensive treatment can lead to progressive weight loss. Recently, omega-3 fatty acids have gained interest for their beneficial effects in several diseases. Moreover, nutritional supplementation enriched with omega-3 FA could potentially maintain body weight in cancer patients undergoing intensive treatment. Aims In this study, the investigators want to evaluate the use of omega-3 FA supplementation as nutritional and the investigators would like to identify potential risk factors, biomarkers and objective measurement tools which can predict therapy-induced cachexia.

Detailed Description
-----------------
Design A prospective, placebo-controlled trial. H&N cancer patients eligible for curative treatment will be randomised to receive standard nutritional support with placebo (15ml/day Sunflower oil, control group) or nutritional support with omega-3 FA supplementation (15ml/day Echium oil, experimental group) during radio(chemo)therapy. All patients will undergo a nutritional screening (Patient-Generated Subjective Global Assessment), a quality of life evaluation (EORTC QLQ C30 & HN35) and will be asked to keep a 3-day food diary at the start of their therapy, and again during the 4th week and the end of therapy. Body composition and grip strength will be measured with bio-electrical impedance (BIA) analysis, Dual X-ray absorptiometry (DXA) and the JAMAR® hydraulic hand dynamometer once at baseline, and again in the 4th week of therapy. Blood samples are collected at baseline, and in the 4th week of therapy to (1) verify compliance rate by measuring fatty acid concentration, (2) verify the presence of potential biomarkers that can predict cachexia and (3) to detect the presence of SNPs associated with severe acute dysphagia. Demographic data, tumour characteristics and therapy-related toxicity will also be collected. Population Newly diagnosed non-metastatic (stage I-IVB) head and neck cancer patients (≥18 or older) eligible for curative primary or adjuvant radiotherapy with or without systemic therapy

Official Title
-----------------
Multi-centric, Placebo-controlled Trial of Omega-3 Fatty Acid Supplementation in Weight Maintenance and Preservation of Lean Body Mass, in (Pre)Cachectic Head and Neck Cancer Patients, Undergoing Curative Radio(Chemo)Therapy

Conditions
-----------------
Cancer Cachexia, Head and Neck Cancer

Intervention / Treatment
-----------------
* Dietary Supplement: BioMega SDA®
* Dietary Supplement: Sunflower oil high oleic


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed squamous cell carcinoma of the head and neck region, generally cancer of the oral cavity, (naso)pharynx and larynx. Cancer of the parotid gland, or nasal cavity and paranasal sinuses are excluded, as well as cT1 N0 M0 tumours of the glottis. Primary cancer or relapse, eligible for primary or adjuvant radiotherapy with or without systemic treatment, with curative intent TNM stage I to IVB, without distant metastases Patients should be older than 18 at the time of enrolment Patients should be able to adequately communicate in Dutch or French Exclusion Criteria: Patients younger than 18 years at the time of recruitment Pregnant or lactating women Patients presenting with another non-cured cancer (PSA or CEA not within normal range as determined by the treating physician) Patients that already underwent a radio(chemo)therapy treatment within the last 6 months Patients taking oral anticoagulants or LMWH at therapeutic doses Patients taking anti-epileptics Patients with an indication of heart failure NYHA 3 or 4, or presence of an implantable cardioverter-defibrillator Patients with a pacemaker will be excluded from BIA-analysis Patients presenting with active intestinal co-morbidity, precluding adequate dietary intake or interfering with the absorption of the nutritional supplements (eg Crohn's disease) Patients with a known eating disorder (eg anorexia nervosa, bulimia nervosa) Patients with uncontrollable diabetes HIV-positive patients Patients with (severe) dementia (DSM-IV criteria) Patients actively taking fish oil, echium oil or omega-3 FA supplements in the last 4 weeks before enrolment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: omega-3 fatty acid supplementation<br>omega-3 fatty acid supplementation (echium oil) | Dietary Supplement: BioMega SDA®<br>* Echium oil, 15ml/day, 2 times per oral 7.5ml sachet/day, during 7-week radio(chemo)therapy<br>|
| Placebo Comparator: standard nutritional support<br>sunflower oil supplementation | Dietary Supplement: Sunflower oil high oleic<br>* Sunflower oil high oleic, 15ml/day, 2 times per oral 7.5ml sachet/day, during 7-week radio(chemo)therapy<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| prevention of therapy-related weight loss | difference between body weight at baseline and end of therapy | 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| determination of beneficial (and possible side) effects of omega-3 FA supplements in general, and specifically on body weight and body composition | measurement of evolution in body composition (baseline - week 4); measurement of evolution in quality of life (baseline - week 4 - end therapy); measurement of adverse events (CTCAE v4.0)in both groups | 7 weeks | 
| establish feasibility, variability and distribution of BIA, DXA and JAMAR® as objective measurement tools of body composition | evolution percentage fat and lean mass (baseline - week 4) as determined by Bio-Elektrical Impedance (BIA) and Dual Energy X-ray Absorptiometry (DXA); evolution grip strength (kg) (baseline - week 4) as determined by JAMAR® hydraulic hand dynamometer | 7 weeks | 
| identification of potential clinical risk factors of cachexia | identification of nutritional parameters (obtained from validated nutritional screeners and PG-SGA), demographic, tumour and therapy characteristics, physical, emotional, financial, functional, nutritional and psycho-social characteristics (obtained from EORTC QLQ C30 & HN35), and body composition measurements (% fat, % lean mass, phase angle obtained from BIA, DXA and hand dynamometer) | 7 weeks | 
| evaluation of the use and reliability of different validated nutritional screening tools in this population | screening with Short Nutritional Assessment Questionnaire (SNAQ), Mini-Nutritional Assessment short-form (MNA-SF), Malnutrition Universal screening tool (MUST), Nutritional risk screening (NRS 2002), Malnutrition screening tool (MST) and the nutrition risk score (NRS); nutritional assessment with Patient Generated - Subjective Global Assessment (PG-SGA) as gold standard | 7 weeks | 
| identification and evaluation of potential biomarkers for therapy-induced cachexia | identification of serum biomarkers and Single Nucleotide Polymorphisms (SNP) | 7 weeks | 
| measurement of difference in quality of life | measurement of quality of life (baseline, week 4, end therapy) with EORTC QLQ C30&HN35 | 7 weeks | 
| dropout and compliance to nutritional supplements | number of sachets consumed; omega-3 fatty acid profile as marker for therapy compliance | 7 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
head and neck cancer, omega-3 fatty acid supplementation, echium oil, weight loss, cancer cachexia, body composition, biomarker, quality of life