Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent side effects caused by antineoplastic agents, with a prevalence from 19% to over 85%. Clinically, CIPN is a mostly sensory neuropathy that may be accompanied by motor and autonomic changes of varying intensity and duration.

Due to its high prevalence among cancer patients, CIPN constitutes a major problem for both cancer patients and survivors as well as for their health care providers, especially because, at the moment, there is no single effective method of preventing CIPN; moreover, the possibilities of treating this syndrome are very limited.

The phycocyanin (PC), a biliprotein pigment and an important constituent of the blue-green alga Spirulina platensis, has been reported to possess significant antioxidant and radical-scavenging properties, offering protection against oxidative stress.

Study hypothesis is that phycocyanin may give protection against oxaliplatin-induced neuropathy in the treatment of gastro intestinal cancers including oesogastric, colo-rectal and pancreatic cancers. This trial will be a randomised placebo-controlled study.

The phycocyanin used in this protocol (Phycocare®) will be 5 times more concentrated than the Spirulysat (food supplement commercialized by Algosource).

It will be administrated during Oxaliplatin based chemotherapy and 3 months after oxaliplatin stopped.

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 cancer including oesogastric, colo-rectal, pancreatic cancers, locally advanced pancreatic cancers 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 (including phytotherapy 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 with thoracic-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 is treated with a monoclonal antibody combined to chemotherapy (bevacizumab or cetuximab or panitumumab or nivolumab or Trastuzumab For patients treated with trastuzumab : patient without HER2 overexpression (defined by positive IHC3 or positive IHC2 and confirmed by a positive FISH result)
• Patient with clinically significant coronaries affection or myocardial infarction within 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 of inflammatory intestinal disease or extended resection of the small intestine or presence 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 any other grade 4, gastro-intestinal perforations or non-gastrointestinal fistulas or intra-abdominal abscesses during the 6 months before randomization.
• For patient treated with bevacizumab: patient with uncontrolled arterial hypertension (systolic pressure >150 mmHg and/or diastolic pressure >100 mmHg) with and without antihypertensive medication. Patients with high hypertension are eligible if antihypertensive medication lowers their arterial pressure to the level specified by the criterion.
• Patient with an history of hypertensive crisis or hypertensive encephalopathy
• Patient with other concomitant malignancy or history of cancer (except in situ carcinoma of the cervix, or non-melanoma skin cancer, treated with curative intent treatment) except if considered in complete remission for at least 2 years before randomization
• Existence of any other pathology, metabolic problem, anomaly during the clinical examination or biological anomaly which may reasonable suspect an underlying pathology which would contra- indicate the use of the study medication or any other risk of complication related to the treatment.
• Any treatment including an experimental drug, or participation in another clinical trial within 28 days before randomization.
• Pregnant women, or women who could possibly be pregnant (or who expect to fall pregnant within 6 months of the end of treatment), or who are breast feeding are not eligible.
• Men and women of child-bearing potential who do not accept to use a highly effective contraceptive (as per currently acceptable institutional standards) or abstinence during the study and for the month after the last administration of the study treatments.
• Persons deprived of liberty or under guardianship.
• Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

The placebo will match as much as possible all the characteristics of the Phycocare®