Clinical trial NCT03146338: Prophylaxis of Magnesium-rich Mineral Water to Prevent Hypomagnesemia Induced by an Anti-EGFR (OPTIMAG)
Official title: Prophylaxis of Magnesium-rich Mineral Water to Prevent Hypomagnesemia Induced by an Anti-EGFR Monoclonal Antibody
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Metastatic Colorectal Cancer
Metastatic Head and Neck Cancer
Keywords: Anti-EGFR
Hypomagnesemia
Magnesium-rich mineral water
Metastatic colorectal or head and neck cancers
Lead sponsor: Weprom
Sponsor class: OTHER
Collaborators: name: Neptune
First posted: 2017-05-09
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Anti-EGFR (Epidermal Growth Factor Receptor) therapies, namely cetuximab and panitumumab, have become standards in the management of metastatic colorectal and head and neck cancers. These therapies are used in daily practice, that requiring to manage their skin and digestive toxicities. However, anti-EGFR are also frequently responsible for hypomagnesemia often neglected and under-treated.

Hypomagnesemia may manifest as asthenia, cramps, muscle weakness, mood disorders. She is often underestimated because they are difficult to identify and accountable by clinicians in the context of cancer under chemotherapy.

There is currently no national or international recommendation on the management of hypomagnesaemia in oncology and medicine in general. There are, however, on the market many nutritional supplements rich in magnesium in the form of tablets or oral solution, in multiple dosages.

These food supplements rich in magnesium are sold without proof of effectiveness. Moreover, the prescription of oral magnesium supplementation adds to the oncology patient an over-medicalization, which can be poorly tolerated at the digestive level, and responsible for diarrhea and a lack of compliance.

The European Food Safety Authority (EFSA) recommends in its opinion on "Dietary reference values for water" to consume 2 liters for women and 2.5 liters for men every day, all sources combined (food and beverages). The drink represent 80% of the water intake, that is about 1.5 Liter per day excluding food. However, there are multiple water marketed or distributed freely, with different compositions. Thus the quantity and quality of the mineral water consumed can influence the metabolism. Rozana® mineral water, has the double advantage of being the French water the most concentrated in magnesium (160 mg / L) and of being lowly concentrated in sulphate, responsible of the laxative power of certain waters.

Instead of adding magnesium supplements with a poor digestive tolerance, to patients with metastatic cancer and often with a heavy treatment , the aim of this study is to evaluate whether a change in oral hydration in quantitative and qualitative terms can decrease the rate of hypomagnesemia in patients treated with anti-EGFR.

Detailed description: Anti-EGFR (Epidermal Growth Factor Receptor) therapies, namely cetuximab and panitumumab, have become standards in the management of metastatic colorectal and head and neck cancers. These therapies are used in daily practice, that requiring to manage their skin and digestive toxicities. However, anti-EGFR are also frequently responsible for hypomagnesemia often neglected and under-treated.

Magnesium remains the fourth cation and the second most important intracellular cation in the body. It is an indispensable cofactor in multiple enzymatic reactions. Hypomagnesemia may manifest as asthenia, cramps, muscle weakness, mood disorders. She is often underestimated because they are difficult to identify and accountable by clinicians in the context of cancer under chemotherapy.

There is currently no national or international recommendation on the management of hypomagnesaemia in oncology and medicine in general. Hypomagnesemia is, in daily practice, mostly undiagnosed or untreated. There are, however, on the market many nutritional supplements rich in magnesium in the form of tablets or oral solution, in multiple dosages.

To date, these food supplements rich in magnesium are sold without proof of effectiveness. The clinical data are very insufficient, and no oral supplementation is reimbursed. Moreover, the prescription of oral magnesium supplementation, often several intakes a day, adds to the oncology patient an over-medicalization, which can be poorly tolerated at the digestive level, and responsible for diarrhea and a lack of compliance. Oral hydration is one of the most prescribed medical advice and remains essential to combat the risk of dehydration in extreme ages. The European Food Safety Authority (EFSA) recommends in its opinion on "Dietary reference values for water" to consume 2 liters for women and 2.5 liters for men every day, all sources combined (food and beverages). The drink represent 80% of the water intake, that is about 1.5 Liter per day excluding food. However, there are multiple water marketed or distributed freely, with different compositions. Thus the quantity and quality of the mineral water consumed can influence the metabolism.

The digestive absorption of magnesium provided by mineral water in a healthy individual was evaluated at around 40 to 50%. Rozana® mineral water, has the double advantage of being the French water the most concentrated in magnesium (160 mg / L) and of being lowly concentrated in sulphate, responsible of the laxative power of certain waters.

Instead of adding magnesium supplements with a poor digestive tolerance, to patients with metastatic cancer and often with a heavy treatment , the aim of this study is to evaluate whether a change in oral hydration in quantitative and qualitative terms can decrease the rate of hypomagnesemia in patients treated with anti-EGFR.

Eligibility criteria: Inclusion Criteria:

1. Patient having either:

   * a metastatic head and neck cancer or in locoregional relapse, proved histologically, authorizing an oral feeding or by gastrostomy or nasogastric tube,
   * a metastatic colorectal cancer, histologically proved, wild-type RAS
2. Patient who must be treated by anti-EGFR for this cancer
3. Age ≥ 18 years
4. Performance Status = 0, 1 or 2
5. Patient affiliated to a social security scheme
6. Patient who have given written consent prior to any specific study-related procedure

Exclusion Criteria:

1. Cerebral metastasis
2. Previous anti-EGFR treatment
3. Patient requiring exclusive parenteral nutrition and hydration
4. Concomitant treatment by radiotherapy
5. Presence of another invasive cancer, other than head and neck or digestive, except basal cell carcinoma or intracervical neoplasia treated
6. Presence of hypomagnesemia at randomization
7. Ongoing oral or intravenous magnesium supplementation within 2 weeks before randomization
8. Patient with grade III or IV diarrhea within 2 weeks before randomization
9. Patient who have had a jejunostomy or ileostomy
10. Patient with constitutional tubulopathy
11. Patient with chronic renal insufficiency (MDRD Clarity \<60 mL / min)
12. Pregnancy or breast-feeding
13. Persons deprived of their liberty or under guardianship
14. Dementia, mental impairment or psychiatric pathology that may compromise the patient's informed consent and / or adherence to the protocol and follow-up of the trial
15. Patient who can not follow protocol for psychological, social, family or geographical reasons

Primary outcomes:
measure: Rate of patients with hypomagnesemia
timeFrame: 3 months
Secondary outcomes:
measure: Median rate of magnesium and hypomagnesemia grade III / IV
timeFrame: 6 months
measure: Proportion of patients with a 20% decrease in magnesemia
timeFrame: 6 months
measure: Incidence of hypomagnesemia after 2 cycles of anti-EGFR treatment
timeFrame: 6 months
measure: The fraction of urinary excretion over 24 hours of magnesium
timeFrame: 6 months
measure: Rate of patient requiring magnesium supplementation
timeFrame: 6 months
measure: Rate of hypomagnesemia at 5 months of treatment
timeFrame: 5 months
measure: Enteral intakes in magnesium
timeFrame: 6 months
measure: Quality of life
timeFrame: 6 months
measure: Compliance
timeFrame: 6 months
measure: Rate of diarrhea and cramps
timeFrame: 6 months
measure: Hypocalcaemia and hypokalemia rates
timeFrame: 6 months
measure: Time until hypomagnesemia occurrence, regardless of grade, and time until grade III / IV hypomagnesemia
timeFrame: 6 months
measure: Progression-free survival
timeFrame: 2 years
measure: Overall survival
timeFrame: 2 years
Other outcomes:
Locations:
city: Lorient
country: France
facility: GHBS Lorient
state: Bretagne
city: Plérin
country: France
facility: CARIO-HPCA Plérin
state: Bretagne
city: Caen
country: France
facility: Centre Maurice TUBIANA
state: Normandie
city: Chambray-lès-Tours
country: France
facility: CORT 37
city: La Roche-sur-Yon
country: France
facility: Centre Hospitalier Départemental
city: Le Mans
country: France
facility: Centre Hospitalier
city: Le Mans
country: France
facility: Centre Jean Bernard
city: Nancy
country: France
facility: Polyclinique de Gentilly
city: Niort
country: France
facility: Centre Hospitalier
city: Pontivy
country: France
facility: Centre Hospitalier Centre Bretagne
city: Tours
country: France
facility: CHRU Tours
city: Vannes
country: France
facility: Centre d'Oncolgie Saint Yves
Study officials:
affiliation: Centre Jean Bernard - Le Mans
name: Hugues BOURGEOIS, MD
role: PRINCIPAL_INVESTIGATOR
References: