Ketogenic Diet for Patients Receiving Treatment for Metastatic Renal Cell Carcinoma

Inclusion Criteria:

1. Subject with histologically-confirmed renal cell carcinoma

2. At least one CT-verified metastasis ≥ 10 mm, not previously irradiated

3. Treatment : PAZOPANIB, SUNITINIB, PEMBROLIZUMAB/AXITINIB or NIVOLUMAB/IPILIMUMAB (for first line), NIVOLUMAB, CABOZANTINIB, AXITINIB, SORAFENIB, TKI anti-VEGF, othertherapy for second and third line of treatment

4. Men and women, aged ≥ 18 years

5. OMS ≤ 1

6. Screening laboratory values must meet the following criteria and should be obtainedprior to commencement of treatment:

7. Hemoglobin ≥ 9 g/dL, neutrophils ≥ 1000 /mm3, platelets ≥ 100 000 /mm3,leukocytes ≥ 2000 /mm3

8. Total bilirubin ≤ 1,5 ULN, ASAT and ALAT ≤ 3 x ULN

9. Creatinine clearance ≥ 30 mL/min, verified proteinuria above or equal to 1g/24hours measured from 24 hours of urine if the urinary protein

10. Corrected calcium ≤ ULN

11. Patient must have signed and dated informed consent

12. Patient must have an internet connection

Exclusion Criteria:

1. Any contraindication to a ketogenic diet : primary carnitine deficiency, fatty acidbeta-oxidation and cytogenesis deficiencies, pyruvate carboxylate deficiency,porphyria

2. Swallowing disorder

3. Important surgical procedure within the 4 weeks before treatment

4. Prior radiotherapy must have been completed at least 2 weeks prior to treatment

5. Pregnant women or breastfeeding

6. Subjects with previous malignancies (except non-melanoma skin cancer and thefollowing endometrial in situ cancers) are excluded unless a complete remission wasachieved at least 3 years prior to study entry and no additional therapy is requiredduring the study period

7. Subjects with symptomatics brain metastases, uncontrolled compression of the spinalcord, carcinomatous meningitis, signs of cerebral or leptomeningeal involvement

8. Uncontrolled blood pressure (SBP >150 mmH et DBP >100 mmHg)

9. Any serious or uncontrolled medical disorder during the last 6 months : hepaticinsufficiency, renal insufficiency, respiratory insufficiency

10. Patients with any severe medical conditions within 6 month prior to inclusion suchas : myocardial infarction, severe/instable angina pectoris, coronary artery bypasssurgery, NYHA III or IV congestive heart failure, stroke or transient ischemicattack

11. Patients with sere medical conditions within 3 month prior to inclusion such as :grade 3 or grade 4 gastrointestinal bleeding, peptic ulcer treatment resistant,esophagitis or ulcerated gastritis, infectious or inflammatory bowel disease,diverticulitis, thrombosis, pulmonary embolism or other uncontrolled thromboembolicevent, unhealed bone fractures

12. Known history of testing positive for human immunodeficiency virus (HIV) or knownacquired immunodeficiency syndrome (AIDS)

13. Malabsorption syndrome

14. Uncontrolled infection

15. QT/QTc interval > 450 msec for men and > 470 msec for women

16. Concomitant treatments : strong inducers of CYP3A4 (DEXAMETHASONE, PHENYTOINE,CARBAMAZEPINE, RIFAMPICINE, RIFABUTINE, RIFAPENTINE, PHENOBARBITAL, and ST. JOHN'SWORT)

17. Social, psychological or medical condition that may interfere with participation inthe study or its evaluation

18. Patient deprived of liberty by judicial or administrative decision

19. Patient with psychiatric treatment under duress

20. Patient subject to legal protection measures

21. Patient unable to give informed consent.