Study Evaluating Neurotoxicity in Patients with Metastatic Gastro Intestinal Cancer Taking Phycocare® or Placebo During Oxaliplatin Based Chemotherapy

Inclusion Criteria:

• Male or female with the age > or = to 18 years old.

• Negative pregnancy test for women with child-bearing potential if applicable (without hysterectomy for example)

• Information given to the patient who must have signed informed consent

• Patient with Histologically or cytologically proven gastro intestinal cancerincluding oesogastric, colo-rectal, pancreatic cancers, locally advanced pancreaticcancers and planned to be treated with oxaliplatin

• Patient with metastatic disease not previously treated

• Patient willing not to take any plant-based therapy during the study (includingphytotherapy and gemmotherapy)

• Previous radiotherapy is authorized if discontinued ≥15 days prior to randomization

• Sites of disease evaluated within 42 days prior C1 day 1 of chemotherapy withthoracic-abdominal-pelvic CT scan (or abdominal-pelvic MRI and chest X-ray)

• Patient with ECOG Performance status 0 or 1

• Patients with a Life expectancy ≥12 weeks

• Laboratory results:

Hematologic function:

polynuclear neutrophils ≥ 1.5.109/L platelets ≥100.109/L haemoglobin ≥9 g/dL

Hepatic function:

transaminases ≤2.5 times upper limit of normal (ULN) (≤5 ULN in case of hepatic metastases), alkaline phosphatases ≤2.5 x ULN (≤5 ULN in case of hepatic metastases), total bilirubin ≤1.5 x ULN

Renal function:

creatinemia clearance >50 ml/min (Cockcroft and Gault)

• Patient with Public Health insurance coverage

Exclusion Criteria:

• Patients with phenylketonuria

• Patients with known meningeal or brain metastases

• Patient previously treated for their metastatic cancer

• Patient previously treated with oxaliplatin

• Patient with specific contraindication or known hypersensitivity to spirulina

• Patient with specific contraindication or known hypersensitivity to oxaliplatin.

• Known allergy or hypersensitivity to antibodies or any preservatives if patient istreated with a monoclonal antibody combined to chemotherapy (bevacizumab orcetuximab or panitumumab or nivolumab or Trastuzumab For patients treated withtrastuzumab : patient without HER2 overexpression (defined by positive IHC3 orpositive IHC2 and confirmed by a positive FISH result)

• Patient with clinically significant coronaries affection or myocardial infarctionwithin 6 months prior to randomization.

• Patient with peripheral neuropathy >1 (CTCAE scale version 5.0).

• Patients with known dihydropyrimidine dehydrogenase (DPD) deficiency.

• Patient with acute intestinal obstruction or sub-obstruction, history ofinflammatory intestinal disease or extended resection of the small intestine orpresence of a colic prosthesis.

• Patient with unhealed wound, active oesogastric or duodenal ulcer, or bone fracture

• Patient with an history of abdominal fistulas, trachea-esophageal fistulas or anyother grade 4, gastro-intestinal perforations or non-gastrointestinal fistulas orintra-abdominal abscesses during the 6 months before randomization.

• For patient treated with bevacizumab: patient with uncontrolled arterialhypertension (systolic pressure >150 mmHg and/or diastolic pressure >100 mmHg) withand without antihypertensive medication. Patients with high hypertension areeligible if antihypertensive medication lowers their arterial pressure to the levelspecified by the criterion.

• Patient with an history of hypertensive crisis or hypertensive encephalopathy

• Patient with other concomitant malignancy or history of cancer (except in situcarcinoma of the cervix, or non-melanoma skin cancer, treated with curative intenttreatment) except if considered in complete remission for at least 2 years beforerandomization

• Existence of any other pathology, metabolic problem, anomaly during the clinicalexamination or biological anomaly which may reasonable suspect an underlyingpathology which would contra- indicate the use of the study medication or any otherrisk of complication related to the treatment.

• Any treatment including an experimental drug, or participation in another clinicaltrial within 28 days before randomization.

• Pregnant women, or women who could possibly be pregnant (or who expect to fallpregnant within 6 months of the end of treatment), or who are breast feeding are noteligible.

• Men and women of child-bearing potential who do not accept to use a highly effectivecontraceptive (as per currently acceptable institutional standards) or abstinenceduring the study and for the month after the last administration of the studytreatments.

• Persons deprived of liberty or under guardianship.

• Psychological, familial, sociological or geographical condition potentiallyhampering compliance with the study protocol and follow-up schedule.