Clinical trial NCT05025826: Study Evaluating Neurotoxicity in Patients With Metastatic Gastro Intestinal Cancer Taking Phycocare® or Placebo During Oxaliplatin Based Chemotherapy
Official title: Randomized, Double-blind, Multicenter Placebo-controlled Study Evaluating Neurotoxicity in Patients With Metastatic Gastro Intestinal Cancer Taking Phycocare® or Placebo During Oxaliplatin Based Chemotherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Metastatic Gastric Cancer
Keywords: Oxaliplatin based chemotherapy
neurotoxicity
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
Collaborators: name: Algosource
First posted: 2021-08-27
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Arm A: Phycocare Arm B: Placebo
Primary purpose: PREVENTION

Brief 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.

Detailed description: 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.

Primary outcomes:
measure: Demonstrate a 50% decrease of the grade> or = 2 neurotoxicity at 4 months after oxaliplatin-based chemotherapy start in the PHYCOCARE arm
timeFrame: 4 months after oxaliplatin-based chemotherapy start
Secondary outcomes:
measure: Comparison between the two arms of percentage of patients who stopped oxaliplatin for neurological toxicity
timeFrame: last day of chemotherapy
measure: Comparison between the two arms of percentage of patients with oxaliplatin dose decrease
timeFrame: last day of chemotherapy
measure: Comparison between the two arms of Neurological toxicities according to the Common Terminology Criteria for adverse Event (CTCAE) v5.0
timeFrame: end of study visit (an average of 9 months after cycle 1 day1)
measure: Comparison between the two arms of Overall Toxicity (including hematological toxicity, gastro-intestinal toxicity, etc…)
timeFrame: end of study visit (an average of 9 months after cycle 1 day1)
measure: Comparison between the two arms of Patient 's Quality of Life according with EORTC-QLQ-C30
timeFrame: end of study visit (an average of 9 months after cycle 1 day1)
measure: Comparison between the two arms of Neurological toxicities
timeFrame: end of study visit (an average of 9 months after cycle 1 day1)
Other outcomes:
Locations:
city: Cholet
country: France
facility: Centre Hospitalier de Cholet
city: Clermont-Ferrand
country: France
facility: Clermont-Ferrand UH
city: Dijon
country: France
facility: DIJON UH
city: La Roche-sur-Yon
country: France
facility: Chd La Roche Sur Yon
city: Nantes
country: France
facility: Hôpital le Confluent
city: Nantes
country: France
facility: Nantes Uh
city: Rennes
country: France
facility: Saint Gregoire Clinique
city: Saint-Nazaire
country: France
facility: Mutaliste Clinic Saint Nazaire
city: Suresnes
country: France
facility: Foch Suresnes Hosptial
Study officials:
affiliation: NANTES UH
name: Yann TOUCHEFEU, Professor
role: PRINCIPAL_INVESTIGATOR
References: