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NCT Number: NCT06896552

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.

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.

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Key information

Conditions

Cancer Adenocarcinoma Carcinoma Carcinoma, Renal Cell Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Immunotherapy Ketogenic Diet Kidney Diseases Kidney Neoplasms Male Urogenital Diseases Melanoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year–100 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Ketogenic diet

Dietary Supplement

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 that standard diets do not.

Primary outcomes

  1. 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.

  2. 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.

  3. 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

  1. Overall response rate according to RECIST v1.

    Time frame: End of treatment at 10 weeks

  2. Adherence to Dietary Interventions - Ketone Level Measurements

    Time frame: Weekly from Baseline (Week 0) to Week 10

    Ketone Level Measurements: Ketone levels will be measured to assess whether participants are in a state of ketosis (>0.3 Mm), indicating adherence to the ketogenic diet.

    Data Analysis: Ketone levels will be analyzed to determine adherence to the ketogenic diet.

  3. Change in Body Weight (kg) Over the Study Period

    Time frame: Baseline (Week 0), Week 4, Week 10, and Week 14 (±1 week).

    Body weight (in kilograms) will be measured using a calibrated digital scale at specified time points. Changes from baseline will be reported as absolute weight differences and percentage change

  4. 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).

    Quality of life will be assessed using the EORTC QLQ-C30 questionnaire, a validated tool for measuring cancer patients' health-related quality of life.

    The EORTC QLQ-C30 consists of 30 items, evaluating functional scales (physical, role, emotional, cognitive, and social functions), symptom scales (fatigue, pain, nausea/vomiting, etc.), and global health status.

    Scores range from 0 to 100. Higher scores on functional and global health scales indicate better quality of life.

    Higher scores on symptom scales indicate greater symptom burden (worse outcome).

    Changes from baseline to Week 10 will be reported as mean score differences.

  5. Fecal microbiome

    Time frame: At enrollment (baseline) and at the end of treatment at 10 weeks

    Such as, but not limited to, 16S analysis

  6. Sarcopenia

    Time frame: At enrollment (baseline) and at the end of treatment at 10 weeks

    Assessed using CT scans of the axial L3 sections and customized software

  7. Body composition-- Fat Mass and Lean Mass

    Time frame: Monthly (week 0, 4, 10 ±1 week).

    This measure will assess changes in body composition using bioelectrical impedance analysis (BIA).

    Fat Mass(kg) and Lean Mass (kg): Body composition will be assessed using Bioelectrical Impedance Analysis (BIA) to measure fat mass(kg) and lean mass(kg).

    Data Analysis: Changes in fat mass and lean mass will be reported as absolute values and fold-changes over time.

  8. Resting Energy Expenditure (REE)

    Time frame: Monthly (week 0, 4, 10 ±1 week).

    Measured by indirect calorimeter - Q-NRG

  9. The Rate of immune-related adverse events

    Time frame: From enrollment to the end of treatment at 10 weeks

Study contacts

Contact information is provided by the study sponsor or research team.

Keren Porper, M.Sc

CONTACT

[email protected]

97239377990

Sponsors and collaborators

Lead sponsor

Rabin Medical Center

Other

Registry information

Official study title

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

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Mar 26, 2025
Registry last updated
Mar 26, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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