The purpose of this study is to assess objective response rate (partial and complete response) of Nivolumab and Ipilimumab concomitant to a special diet (ketogenic diet, continuous or discontinuous) or standard diet with or without BHB according to RECIST v1.1 at 8 weeks.
After being informed about the study and potential risks, all patients giving informed consent will undergo a 10 days screening period to determine eligibility for study entry. At week1day1, patients who meet the eligibility requirements will be enrolled in to : * Arm A : continuous ketogenic diet for 3 months * Arm B : discontinuous ketogenic diet (15 days on, 15 days off) for 3 months * Arm C : oral liquid ketone supplement BHB monoester, 15 days-on 15 days off during 3 months. * Arm D : standard diet (without any diet restrictions). and follow up as in arms A, B, C. All patients will receive Nivolumab plus Ipilimumab according to practical routine.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
3
ARM A : continuous ketogenic diet
ARM B : discontinuous ketogenic diet
ARM C : BHB supplementation
Gustave Roussy
Villejuif, Val-de-Marne, France
Hôpital Européen Georges Pompidou
Paris, France
Hôpitaux Cochin-Port-Royal
Paris, France
Objective response rate
Preliminary activity will be assessed by measuring objective response rate (ORR) (partial/complete response) of Nivolumab plus Ipilimumab concomitant to a special diet (KD continuous or discontinuous) or standard diet (SD) with or without (BHB) according to RECIST v1.1 at 8 weeks.
Time frame: at 8 weeks after diet initiation.
Safety of Nivolumab plus Ipilimumab concomitant to a special diet
the safety of Nivolumab plus Ipilimumab concomitant to a special diet (ketogenic diet, continuous or discontinuous) or standard diet (SD) with or without BHB will be measured by the rate of all and grade 3-4 adverse events (AEs) according to CTCAEv4, and compare the rate to historical data.
Time frame: Events reported from the first day of diet and up to and including 100 days following the last day of diet could be included in estimating this incidence rate.
Assessment of weight
Assessment of weight in kilograms by baseline test and follow up in order to evaluate the impact of the diet concomitant to immunotherapy on nutritional status, muscle mass, and sarcopenia.
Time frame: from the first day of diet and up to 2 years from diet initiation
Assessment of albuminemia
Assessment of albuminemia in g/L in order to evaluate the impact of the diet concomitant to immunotherapy on nutritional status, muscle mass, and sarcopenia.
Time frame: from the first day of diet and up to 2 years from diet initiation
Assessment of prealbuminemia
Assessment of prealbuminemia in g/L in order to evaluate the impact of the diet concomitant to immunotherapy on nutritional status, muscle mass, and sarcopenia.
Time frame: from the first day of diet and up to 2 years from diet initiation
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Assessment of C reactive protein
Assessment of C reactive protein in mg/L in order to evaluate the impact of the diet concomitant to immunotherapy on nutritional status, muscle mass, and sarcopenia.
Time frame: from the first day of diet and up to 2 years from diet initiation
Assessment of sarcopenia
Sarcopenia will be assessed according to SliceOmatic software V5.0 and preestablished thresholds of skeletal muscle tissue (-29 to +150 Hounsfield units). Axial L3 sections will be used to measure the total muscle area (TMA) and calculate skeletal muscle index (SMI, cm²/m²). Sarcopenia is defined as SMI lower than a sex-based threshold (\<55.4 in men and \<38.9 in women).
Time frame: from the first day of diet and up to 2 years from diet initiation
Assessment of Quality of Life (QoL)
explore the evolution of Patient Reported Outcomes using EORTC QLQ 30 file in all treated patients.
Time frame: At screening and 9 weeks after diet initiation
progression-free survival assessment
PFS is specified as the time between the date of the starting of the diet and the first date of documented progression, based on assessments (as per RECIST v1.1 criteria), or death due to any cause.
Time frame: from the first day of diet and up to 2 years from diet initiation
Sarcopenic event-free survival (SFS)
SFS will be estimated from intervention starting.
Time frame: from the first day of diet and up to 2 years from diet initiation
Overall survival (OS)
OS is specified as the time between the date of the starting of the diet and the date of the death whatever the cause.
Time frame: from the first day of diet and up to 2 years from diet initiation