Clinical trial NCT04316520: Ketogenic Diet for Patients Receiving Treatment for Metastatic Renal Cell Carcinoma
Official title: A Pilot Study Evaluating the Tolerability of a Ketogenic Diet With Vitamin Supplementation for Patients Receiving Treatment for Metastatic Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metastatic Renal Cancer
Keywords: metastatic renal cancer
ketogenic diet
immunotherapy
first line treatment
targeted therapy
Lead sponsor: University Hospital, Angers
Sponsor class: OTHER_GOV
Collaborators: name: Vitaflo International, Ltd
First posted: 2020-03-20
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the tolerance of one year of ketogenic diet associated with vitamin supplementation in patients treated for a metastatic renal cell carcinoma.

Detailed description: This research study is a pilot study evaluating the tolerance of a ketogenic diet associated with a standard of care in patient with metastatic renal cell carcinoma.

The drugs involved in this study could be NIVOLUMAB + IPILIMUMAB, PEMBROLIZUMAB + AXITINIB, SUNITINIB or PAZOPANIB.

Cancer cells are known to have an increased glycolytic activity that allows them to product energy from anaerobic degradation of glucose. A ketogenic diet places the body in ketosis state. It forces the body to burn fat instead of glucose. Fat metabolism occurs via the mitochondrial oxidative phosphorylation. By reducing sugar intake and regulating energy metabolism, the ketogenic diet could contribute to limit tumor progression.

This diet will be introduced during one year, patient will be monitored closely with biological tests and radiological assessments every three month.

Eligibility criteria: 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, other therapy 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 obtained prior to commencement of treatment:

   1. Hemoglobin ≥ 9 g/dL, neutrophils ≥ 1000 /mm3, platelets ≥ 100 000 /mm3, leukocytes ≥ 2000 /mm3
   2. Total bilirubin ≤ 1,5 ULN, ASAT and ALAT ≤ 3 x ULN
   3. Creatinine clearance ≥ 30 mL/min, verified proteinuria above or equal to 1g/24 hours measured from 24 hours of urine if the urinary protein
   4. Corrected calcium ≤ ULN
7. Patient must have signed and dated informed consent
8. Patient must have an internet connection

Exclusion Criteria:

1. Any contraindication to a ketogenic diet : primary carnitine deficiency, fatty acid beta-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 the following endometrial in situ cancers) are excluded unless a complete remission was achieved at least 3 years prior to study entry and no additional therapy is required during the study period
7. Subjects with symptomatics brain metastases, uncontrolled compression of the spinal cord, 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 : hepatic insufficiency, renal insufficiency, respiratory insufficiency
10. Patients with any severe medical conditions within 6 month prior to inclusion such as : myocardial infarction, severe/instable angina pectoris, coronary artery bypass surgery, NYHA III or IV congestive heart failure, stroke or transient ischemic attack
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 thromboembolic event, unhealed bone fractures
12. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired 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'S WORT)
17. Social, psychological or medical condition that may interfere with participation in the 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.

Primary outcomes:
measure: Tolerance of one year of ketogenic diet 2:1
timeFrame: 1 year
Secondary outcomes:
measure: Compliance of ketogenic diet
timeFrame: 1 year
measure: Progression free survival according to RECIST 1.1 at 2 years
timeFrame: 2 years
measure: Overall survival at 2 years
timeFrame: 2 years
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU Angers
Study officials:
References: