Prevention of Oxaliplatin-induced Neuropathic Pain by a Specific Diet

Study Overview
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Brief Summary
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Use lay language. Oxaliplatin is a reference anticancer drug in the treatment of colorectal cancer. However, its use is hampered by a specific neurotoxicity, which is characterized by acute thermal hypersensitivity, notably to cold temperatures, and by chronic neuropathy appearing with the repetition of chemotherapy cycles. To this date there is no effective therapy able to prevent and/or to treat these adverse drug reactions. So oncologists are sometimes strained to decrease anticancer doses or to stop chemotherapy; Previously, a polyamine deficient diet has been able to prevent acute oxaliplatin-induced hypersensitivity in animals. So we hypothesizes that a specific nutritional therapy, a polyamine deprived diet, may prevent acute oxaliplatin-induced hypersensitivity in patients.

Detailed Description
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This is a prospective, single-center, controlled and interventional study with two parallel groups randomized in single-blind. After obtaining informed consent, all included patients will be randomized, either: in the group with a polyamines depleted diet : 2-4 cans per day of Polydol® (oral alimentation without polyamines), associated to predefined menus low in polyamines, according to the chemotherapy cycle and for 107 days in the control group with a normal polyamines containing diet: 1 can per day of Polydol® associated with predefined menus with normal average in polyamines and for 107 days. Randomization will be performed by considering stratification on the tumor presence or not, because it is one of the polyamines source (Linsalata and Russo, 2008) and could influence the results in the study. In addition, patient compliance will be collected in the case report form all along the study, and included in the statistical analysis of the study.

Official Title
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Prevention of Oxaliplatin-induced Neuropathic Pain by a Specific Diet

Conditions
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Neuropathy, Digestive Cancer System

Intervention / Treatment
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* Behavioral: Polyamines depleted diet, associating Polydol® cans and predefined menus low in polyamines


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Patients affected by gastrointestinal cancer, without cytotoxic neurotoxic chemotherapy, had to receive FOLFOX 4 chemotherapy (folinic acid + 5-FU + oxaliplatin) in the adjuvant, neoadjuvant or palliative situation with an expected period of 8 cures of treatment or 4 months. Patients having given their written, free and informed consent Patient's members of a social security scheme Patients not having participated in another clinical trial within 15 days before its baseline (possibility of participating and / or participate in an observational trial) Effective contraception for patients, male or female, in childbearing age. Neutrophils > 2.109/L and/or platelet > 100.109/L before the first treatment cycle Exclusion Criteria: - Patient which cannot receive FOLFOX 4 whatever the reason Patients < 18 years old and > 70 years old Malnourished patient (French National Authority for Health, 2003) Patients with all or part of an upper limb amputation Diabetic patient Patients with neuropathy Oral nutrition impossible Painful procedures scheduled after the baseline (e.g. surgical excision) Neurological disorders (e.g. parkinsonism, stroke ...) Alcohol consumption upper 3 alcohol units (30 g) for men and upper 2 alcohol units (20 g) for women Patients having already received cytotoxic neurotoxic chemotherapy (taxanes, platinum salts or vinca alkaloids) Patients treated for another cancer within 5 years except basal cell skin carcinoma or in situ cervical cancer Any unbalanced progressive disease (hepatic failure, renal insufficiency (creatinine clearance <30 mL / min), respiratory failure, congestive heart failure, myocardial infarction within the past 6 months ...) Patients requiring Ca2 + or Mg2 + perfusions Hypersensitivity or allergy known about one of study product's component Pregnant woman or breastfeeding woman Legal disability (person deprived of liberty or under guardianship) Patients for psychological, social, family or geographical reasons can not be monitored regularly and / or be compliant with the requirements of the study Patients already included in another clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: polyamines depleted diet<br>• in the group with a polyamines depleted diet : 2-4 cans per day of Polydol® (oral alimentation without polyamines), associated to predefined menus low in polyamines, according to the chemotherapy cycle and for 107 days | Behavioral: Polyamines depleted diet, associating Polydol® cans and predefined menus low in polyamines<br> <br> |
| Other: normal polyamines containing diet<br>• in the control group with a normal polyamines containing diet: 1 can per day of Polydol® associated with predefined menus with normal average in polyamines and for 107 days. | Behavioral: Polyamines depleted diet, associating Polydol® cans and predefined menus low in polyamines<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cold pain thresholds |  | day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cold pain thresholds |  | day -7, 0, 2, 14, 16, 28, 30, 42, 70, 72, 98, 100, 154 | 
| Heat pain thresholds |  | day -7, 0, 2, 14, 16, 28, 30, 42, 70, 72, 98, 100, 154 | 
| DN4 (Douleur Neuropathique en 4 Questions) scores |  | day -7, 0, 2, 14, 16, 28, 30, 42, 70, 72, 98, 100, 154 | 
| HADS (Hospital Anxiety and Depression Scale) score |  | day -7, 0, 14, 28, 42, 98, 154 | 
| Adverse drug reactions (CTCAE (Common Terminology Criteria for Adverse Events)) |  | day 0, 2, 14, 16, 28, 30, 42, 70, 72, 98, 100, 154 | 
| Cancer response |  | day 154 | 
| Oxaliplatin dose intensity |  | day 154 | 
| Erythrocyte polyamine levels |  | day -7, 0, 14, 28, 42, 70, 98 | 
| NPSI ( Neuropathic Pain Symptom Inventory)scores |  | day -7, 0, 2, 14, 16, 28, 30, 42, 70, 72, 98, 100, 154 | 
| QLQ-C30 (Quality of Life questionnaire C30)scores |  | day -7, 0, 2, 14, 16, 28, 30, 42, 70, 72, 98, 100, 154 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Allodynia;, Anticancer drug;, Oxaliplatin;, Digestive cancer system, Acute oxaliplatin-induced hypersensitivity, Hyperalgesia;, Dysesthesia, Polyamines depleted diet