Trial Information

Chimiodiet Study:Impact of Early and Active Nutritional and Dietary Management on grade3 or More Toxicities Induced by Chemotherapy and Targeted Therapies Administered to Patients as First Intention for Non Surgical Metastatic Colorectal Cancer.

The "Nutricancer study" carried out on 2,000 French patients showed a malnutrition
prevalence rate of 39% in cancer patients. Malnutrition is an independent risk factor for
hospital-acquired infections. It also increases the complication rate following surgery,
chemotherapy and radiotherapy. It may require a reduction in chemotherapy dosage, thus
decreasing the effectiveness of treatment. It increases the length of hospital stays and the
cost of care, and has a negative impact on the quality of life of patients (2, 3).
Nutritional management is not sufficient. Close to 60% of patients included in the
Nutricancer study reported that they had received no nutritional support. Yet, the benefits
of nutritional support in perioperative care for surgical colorectal cancers is well
established. A recent study suggests that early and active nutritional support in rectal
cancer patients reduces the risk of malnutrition, complications from radiotherapy and
increases the quality of life of patients. Close to half of patients receiving FOLFOX or
FOLFIRI type chemotherapies for metastatic colorectal cancer (CRC) develop a grade 3
toxicity. Our hypothesis is that active nutritional support during chemotherapy for
metastatic colorectal cancer will permit the sustainability of intakes and the nutritional
status of patients and lead to a reduction in complications, an improvement in quality of
life and a reduction in the length of hospital stays.

The goal of our study is to show that early and active nutritional and dietary management
(early nutritional support for short) during chemotherapy for metastatic colorectal cancer
decreases the risk of malnutrition, reduces chemotherapy toxicity, improves quality of life
and decreases the length of hospital stays.

The main evaluation criteria of the study will be the frequency of grade 3 or more toxicity
in patients receiving active nutritional support during first line chemotherapy and/or
targeted therapy for non surgical metastatic colorectal cancer.

Experimental framework: This is a prospective, multicentre, open, sample-based clinical
trial. Patients eligible for the study must have been diagnosed with non surgical metastatic
colorectal cancer and be planned to receive 5FU/oxaliplatine or 5FU/irinotecan based
chemotherapy, associated or not with targeted therapy. The main exclusion criteria are
severe malnutrition, adjuvant radiotherapy, artificial nutrition, pregnancy and
breastfeeding, another severe active disease and participation in another clinical trial.

The ChimioDiet study will be proposed during the consultation meant to set up chemotherapy.
Selected patients will be randomly assigned to two groups:

- Group I: patients receiving active nutritional support from the first chemotherapy
session.

- Group II: patients initially receiving no active nutritional support. Random assignment
of patients to groups will be automatically generated by the e-CRF software, taking
into account the need for stratification according to research centre and chemotherapy
type.

An evaluation of nutritional status will be carried out every two weeks (weight, appetite
and intake record). Patients with malnutrition or dietary intakes below 50% of recommended
daily intake over 2 consecutive consultations will receive a protein- and calorie-rich oral
supplement or, if required, enteral or parenteral artificial nutrition. All undesirable
effects of chemotherapy will be recorded. Patients will be required to fill out a quality of
life questionnaire (EORTC QLQ-C30) upon selection for inclusion in the study and every three
months thereafter.

The analysis of the main judgement criteria will rely on a logistic regression. Measured
outcome will be the occurrence of a grade 3 or more toxicity. The main explanatory variables
will be the group to which the patient has been assigned (early and active nutritional
support or not). The analysis will also take into account the main stratification
parameters, namely treatment centre and type of chemotherapy.

Description of active nutritional support: Early and active nutritional support is mainly
concerned with maintaining protein and energy intake levels despite chemotherapy. A
part-time nutritionist will be assigned to each research centre. She will cover active
nutritional support during a one-hour consultation and assist the investigating oncologist
in filling out the e-CRF data. A two-day meeting prior to the beginning of the study will
enable the standardization of active nutritional support strategy across all research
centres:

- The nutritionist will explain the consequences of the side effects of chemotherapy on
appetite levels and nutritional status.

- Spontaneous oral intake and eating habits will be assessed based on a qualitative and
quantitative 3-day food record.

- Then the nutritionist will explain to patients how to adapt their diet (fortification,
portion control etc.) according to personal preferences and dietary habits, appetite
fluctuation and side effects.

- A booklet containing an overview of the nutritional counsel, recipe ideas, an example
of a daily menu, energy equivalence tables and specific diet and hygiene tips for each
possible side effects of chemotherapy will be given to all patients.

- During each consultation, patients will be weighed, appetite and food intake will be
evaluated (24-hour record except for prospective 3-day record of V0, V3, V6, V9, V12,
V13 and V14 consultations), chemotherapy side effects will be recorded and nutritional
counsel will be adapted to each patient's individual situation. In case of decrease in
food intake and/or weight loss, a protein- and energy-rich oral supplement will be
given.

In both groups, if a patient exhibits signs of malnutrition (weight loss >5% over a
one-month period or > 10% in total) and/or food intake less than 50% of estimated daily
requirements, an oral supplement will be given after approval of the oncologist. If this
measure is insufficient, artificial nutrition (enteral or parenteral) will be considered.