Efficacy of an Oral Immunomodulatory Nutrient on Survival During Postoperative Concomitant Chemoradiotherapy in Head and Neck Cancer

Double-blind Multicenter Phase III Trial Evaluating the Efficacy of an Oral Immunomodulatory Nutrient on Survival During Postoperative Concomitant Chemoradiotherapy in Head and Neck Squamous Cell Carcinoma (HNSCC)

The investigators designed a prospective randomized double-blind trial to determine if the oral immunomodulating formula could improve the disease-free survival rate in high-risk locally-advanced head and neck Squamous Cell Carcinoma patients treated with Chemoradiotherapy.

The primary objective is to evaluate the efficacy on disease-free survival of a formula enriched with L-arginine, omega-3 fatty acids, and ribonucleic acids, taken for 5 days before each cycle of chemotherapy, in patients with high-risk locally-advanced HNSCC treated with postoperative concomitant chemoradiotherapy (CRT).

This study is a national, multicentric double blinded, randomised phase III trial. A total of 306 patients (102 patients in group control vs 204 patients in group Oral Impact®) will be required including 10% of lost-to-follow-up patients.

An immunomodulating oral supplementation compound (Oral Impact®) is compared to an isocaloric isonitrogenous control. The compound to be assessed contains 334kcal/bag and 18.1g of proteins, as well as immunomodulatory nutrients such as L-Arginine, RNA and omega-3. The control has the same formula to that of the Oral Impact®, but not enriched with specific nutrients. Each patient has to take Oral Impact® or a sip feed control during 5 days before each cycle of chemotherapy.

DFS will be measured from the time of randomization to the time of the first evidence of progression (local, regional, metastatic, or second primary) or death from any cause. Patients alive without carcinologic event were censored at last follow-up date.

Patients treated with postoperative CRT are expected to have a 2-year DFS rate of 60% without specific diet (pControl).

Including a ratio 1:2, an expected recruitment of 90 patients per year, the current study will require 131 events to detect an absolute improvement of 15% (HR=0.56, pExperimental=75%) with 0.90 statistical power using a two-sided test and a significance level of 0.05.

A total of 306 patients (102 vs 204) will be required including 10% of lost of follow-up patients.

The inclusion period would be 4 years, for an expected total duration of study about 8 years.

Inclusion Criteria:

• Surgically resected primary squamous cell carcinomas (HNSCC) of the hypopharynx, oropharynx, larynx and oral cavity with pathological stage pT1-2 pN+ (pathological stage 1 ou 2 with node) or pT3-4 any pN (pathological stage 3 ou 4 with or without node) (UICC 7th edition, 2010),
• Postoperative concomitant CRT based on radiotherapy and on cisplatinum, 3 cycles, 100mg/m² by cycle,
• Patients who undergone macroscopically complete resection,
• High-risk characteristics patients with one or more following criteria: such as invasion of two or more regional lymph nodes, extracapsular extension of nodal disease or microscopically-involved mucosal margins of resection, perineural involvement, vascular tumor embolism,
• WHO (World Health Organization) performance status 0, 1 or 2,
• Age: 18 years old up to 75 years old including,

Exclusion Criteria:

• Nasopharyngeal, paranasal sinuses, nasal cavity tumours or thyroid cancers
• Sepsis at baseline
• Distant metastasis
• Other immunomodulating diets in the last month before inclusion
• Parenteral nutrition at baseline
• History of hypersensitivity and/or allergy to any component of Oral Impact ®
• Patients with history of malignancies who are not disease-free for more than 5 years.