Single-Center Trial on Ketogenic Diet and Immunotherapy in Advanced Cancer This Study Evaluates the Safety and Effects of a Ketogenic Diet (KD) Combined With Immunotherapy in Adults With Advanced Melanoma, cSCC, or RCC.

Official title

Investigating the Effect of Ketogenic Diet on Immunological Parameters in Advanced Cancer Patients Undergoing Immunotherapy

Overview

This clinical trial aims to evaluate whether a ketogenic diet (KD), when combined with immunotherapy, can improve immune function and treatment outcomes in patients with advanced melanoma, cutaneous squamous cell carcinoma (cSCC), or renal cell carcinoma (RCC). Why Is This Study Important? Immunotherapy is a promising cancer treatment, but not all patients respond well. Research suggests that diet, particularly a high-fat, low-carbohydrate ketogenic diet, may help boost the immune system and make treatments more effective. What Will This Study Examine? Researchers want to understand: Is the ketogenic diet well-tolerated for cancer patients? Does the diet improve immune responses and treatment effectiveness? How Will the Study Work? Participants will be placed into one of two groups: Ketogenic Diet (KD) Group: A structured high-fat, low-carb diet (intermittent schedule: 2 weeks on, 1 week off). Standard Diet (SD) Group: A typical diet with no major changes. Throughout the study, a dietitian will closely support and guide you. Both groups will continue their standard immunotherapy treatment. What Will Participants Do? Write their food intake three times a week to help assess dietary adherence Follow their assigned diet for 10 weeks Have weekly check-ins with a dietitian (in-person at the hospital or via phone) Have weekly blood glucose and ketone level checks using a home device. Provide monthly blood samples to measure immune response during routine immunotherapy infusions Provide stool samples for gut microbiome analysis at the start and end of the study Measure Monthly Weight, body composition, and resting calorie burn Complete quality-of-life questionnaires What Are the Potential Benefits? Improved response to immunotherapy Better understanding of how diet influences cancer treatment Potential for a new supportive strategy for cancer care This study may help uncover ways to enhance cancer treatment through personalized nutrition.

Interventions

• Dietary supplement Ketogenic diet
  Ketogenic Diet as an Adjunct to Immunotherapy: Unlike many trials focused on chemotherapy or targeted therapies, this study specifically investigates the synergistic effects of the ketogenic diet with immune checkpoint inhibitors (ICIs), a promising approach for enhancing immunotherapy efficacy. The diet's high-fat, low-carbohydrate regimen is designed to shift metabolism towards ketone bodies and fatty acid utilization, potentially modulating immune responses and tumor immunogenicity in a way t

Primary outcome measures

• Number of Participants Adhering to the Ketogenic Diet and Experiencing Treatment-Related Adverse Events as Assessed by CTCAE v5.0 [Time frame: From enrollment to the end of treatment at 10 weeks]
• Change in Peripheral Blood Mononuclear Cell (PBMC) Composition at Baseline, During, and Post-Intervention [Time frame: Monthly (week 0, 4, 10 ±1 week).]
• Serum Cytokine Levels at Baseline, During, and Post-Intervention [Time frame: Monthly (week 0, 4, 10 ±1 week).]

Secondary outcome measures (9)

• Overall response rate according to RECIST v1. [Time frame: End of treatment at 10 weeks]
• Adherence to Dietary Interventions - Ketone Level Measurements [Time frame: Weekly from Baseline (Week 0) to Week 10]
• Change in Body Weight (kg) Over the Study Period [Time frame: Baseline (Week 0), Week 4, Week 10, and Week 14 (±1 week).]
• Change in Quality of Life Score Assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) [Time frame: At enrollment (Baseline, Week 0) and at the end of treatment (Week 10).]
• Fecal microbiome [Time frame: At enrollment (baseline) and at the end of treatment at 10 weeks]
• Sarcopenia [Time frame: At enrollment (baseline) and at the end of treatment at 10 weeks]
• Body composition-- Fat Mass and Lean Mass [Time frame: Monthly (week 0, 4, 10 ±1 week).]
• Resting Energy Expenditure (REE) [Time frame: Monthly (week 0, 4, 10 ±1 week).]
• The Rate of immune-related adverse events [Time frame: From enrollment to the end of treatment at 10 weeks]

Eligibility criteria

Inclusion criteria

• • Males and females, age >= 18 years

• Patients with a histologically confirmed melanoma or cSCC or RCC receiving first line treatment with combination nivolumab and ipilimumab /relatlimab or single agent ipilimumab, nivolumab, pembrolizumab, Cemiplimab.
• Able to read, understand, and provide written informed consent
• Willing and able to complete all study-specific procedures and visits
• Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Blood tests:

• Creatinine (Cr) < 1.5 mg/dL.
• Magnesium normal range ( 1.5 -2,6 mg/dL)
• Liver function tests (LFTs) 2.5x upper limit of normal (ULN).
• Neutrophils ≥ 1,000/mm3, platelets ≥ 50,000/mm3, Hb>8 g/dL
• Women of childbearing potential must have a negative β-HCG pregnancy test documented within 1 week of registration.

Exclusion criteria

• • Individuals < 18 years of age

• Unable or unwilling to provide consent
• Other active malignancy (other than adequately treated and cured basal or squamous cell skin cancer, curatively treated in situ disease, or any other cancer from which the patient has been disease free >=2 years)
• Currently consuming a low-carbohydrate (< 130 g/day) or KD or done so in the last 6-months
• Patients currently participating in an interventional or therapeutic clinical trial involving the use of active anti-cancer therapy.
• Active autoimmune diseases requiring active Immune suppressive medications
• Systemic steroid therapy, excluding for replacement due to adrenal insufficiency
• Major surgery within last 3 months
• BMI <18 or >35
• Medical contraindications to the intervention diet as determined by the treating physician.
• Self-reported major dietary restrictions related to the intervention such as irritable bowel syndrome (IBS).
• Patients with a history or active eating disorder
• Uncontrolled Diabetes mellitus or patients receiving insulin
• Known diagnosis of HIV
• Known active hepatitis B or hepatitis C
• Known inborn errors of lipid metabolism
• Sever or uncontrolled Hyperlipidemia (total cholesterol over 400 mg / dL, low-density lipoprotein (LDL) above 300 mg / dL, triglycerides over 500 mg / dl.).
• Pregnant or lactating.
• Patients who have undergone a transplant

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Israel · 1 center

• Rabin Medical Center — Petah Tikva

Publications

• 1. Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359(6382):1350-1355. 2. Hargadon KM, Johnson CE, Williams CJ. Immune checkpoint blockade therapy for cancer: An overview of FDA-approved immune checkpoint inhibitors. Int Immunopharmacol. 2018;62:29-39. 3. Haslam A, Prasad V. Estimation of the percentage of US patients with cancer who are eligible for and respond

Identifiers

NCT: NCT06896552 · 0046-25-RMC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗