study evaluating neurotoxicity in patients with metastatic gastro intestinal cancer taking phycocare® or placebo during oxaliplatin based chemotherapy

Conditions: Metastatic Gastric Cancer

Summary: 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.

Eligibility criteria:
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.

Keywords: oxaliplatin based chemotherapy neurotoxicity