Investigating the Effect of Ketogenic Diet on Immunological Parameters in Advanced Cancer Patients Undergoing Immunotherapy
Trial Snapshot
- Phase
- Phase 1
- Status
- Not yet recruiting
- Sponsor
- Rabin Medical Center
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Number of Participants Adhering to the Ketogenic Diet and Experiencing Treatment-Related Adverse Events as Assessed by CTCAE v5.0
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 100 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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 ≤
- •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
Arms & Interventions
Ketogenic Diet (KD) Group: A high-fat, low-carb diet (intermittent schedule: 2 weeks on,1 week off))
Seven days (±2 days) before first dose of immunotherapy, patients will receive instructions to follow KD. The KD composition: 5-10% of the calories from carbohydrate, 20-30% protein and 60-70% fat. No calorie restriction will be applied, and patients will be instructed to eat to satiety. Supplemental MCT (medium chain triglyceride) oil or /and ketocal powder (Nutricia) will be added at the dietician's discretion in order to promote ketone production. During the period off the KD, the participants will be instructed to gradually follow standard diet composition (50-60% of the calories from carbohydrate, 15-20% protein and 20-30% fat). Diet protocol will be given to the patient along with specific menu suggestions for each individual.
Intervention: Ketogenic diet (Dietary Supplement)
Standard Diet (SD) Group: A typical diet with no major changes.
Outcomes
Primary Outcomes
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
This measure will assess the feasibility and tolerability of the ketogenic diet (KD) in cancer patients undergoing immunotherapy by evaluating: Diet Adherence: The number of participants who maintain KD for at least 80% of the study duration, based on dietary intake logs and ketone level measurements. Tolerability: The number of participants experiencing treatment-related adverse events (AEs), as assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The severity and frequency of AEs will be documented and categorized.
Change in Peripheral Blood Mononuclear Cell (PBMC) Composition at Baseline, During, and Post-Intervention
Time Frame: Monthly (week 0, 4, 10 ±1 week).
This measure will evaluate changes in immune cell composition in response to the ketogenic diet (KD) and immunotherapy. PBMC Composition: Assessed using cytometry by time-of-flight (CyTOF) to characterize shifts in immune cell subsets (e.g., T cells, natural killer cells, monocytes). Data Analysis: Changes from the baseline will be reported as absolute values and fold-changes over time.
Serum Cytokine Levels at Baseline, During, and Post-Intervention
Time Frame: Monthly (week 0, 4, 10 ±1 week).
This measure will evaluate changes in cytokine levels in response to the ketogenic diet (KD) and immunotherapy. Serum Cytokine Levels: Quantified using multiplex immunoassays to measure the concentrations of key cytokines, such as IL-2, IFN-γ, TNF-α, and IL-10. Data Analysis: Changes from baseline will be reported as absolute values and fold-changes over time.
Secondary Outcomes
- Overall response rate according to RECIST v1.(End of treatment at 10 weeks)
- Adherence to Dietary Interventions - Ketone Level Measurements(Weekly from Baseline (Week 0) to Week 10)
- Change in Body Weight (kg) Over the Study Period(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)(At enrollment (Baseline, Week 0) and at the end of treatment (Week 10).)
- Fecal microbiome(At enrollment (baseline) and at the end of treatment at 10 weeks)
- Sarcopenia(At enrollment (baseline) and at the end of treatment at 10 weeks)
- Body composition-- Fat Mass and Lean Mass(Monthly (week 0, 4, 10 ±1 week).)
- Resting Energy Expenditure (REE)(Monthly (week 0, 4, 10 ±1 week).)
- The Rate of immune-related adverse events(From enrollment to the end of treatment at 10 weeks)
Investigators
Gal Markel
MD Ph.D. MBA, Deputy Director of Rabin Medical Center, and Director of Davidoff Center Rabin Medical Center, Full Professor of Clinical Microbiology & Immunology at the Sackler Faculty of Medicine, Tel Aviv University.
Rabin Medical Center