Ketogenic Dietary Intervention to Improve Response to Immunotherapy in Patients With Metastatic Melanoma and Metastatic Kidney Cancer

Phase I Study of the Safety and Feasibility of a Ketogenic Dietary Intervention to Improve Response to Immunotherapy

This phase I trial studies how well a ketogenic dietary intervention works to improve response to immunotherapy in patients with melanoma and kidney cancer that has spread from where it first started (primary site) to other places in the body (metastatic). A ketogenic diet (KD) means eating fewer carbohydrates and more fats. The purpose is to use ketones (normal breakdown from fat) instead of glucose (sugar) as an energy source. Researchers want to see whether a ketogenic diet can improve tumor response in patients receiving immune checkpoint inhibitors (ICI). ICI are newer treatment options that help the immune system better fight some cancers. Following a KD may improve tumor response in patients with metastatic melanoma and metastatic kidney cancer treated with ICI.

Study Overview

• Status: Suspended
• Conditions: Metastatic Renal Cell Carcinoma; Metastatic Cutaneous Melanoma; Stage IV Renal Cell Cancer AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8
• Intervention / Treatment: Other: Questionnaire Administration; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Other: Dietary Intervention; Other: Educational Activity; Other: Glucose Measurement; Other: Ketone Measurement; Other: Best Practice

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the safety and feasibility of establishing a ketogenic dietary intervention trial with longitudinal biospecimen collection in the Ohio State University Comprehensive Cancer Center (OSUCCC) cutaneous and genitourinary oncology clinics.

EXPLORATORY OBJECTIVE:

I. To assess whether the microbiome (binary, high versus [vs] low diversity) mediates the relationship between time in ketosis (days with peripheral blood beta-hydroxybutyric acid [BHB] > 0.5 mM) and tumor size over the course of treatment.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo a ketogenic dietary intervention with personalized coaching from a dietician about the KD, which includes extensive educational and ongoing support on the KD and continuous ketone monitoring by talking to a dietician directly, with the ability to text a dietician at any time and expect a response within 12 hours over 24weeks. Patients also undergo daily blood glucose and ketone monitoring, undergo computed tomography (CT), undergo blood sample collection and may undergo stool sample collection on the study.

ARM II: Patients follow a standard of care diet on the study.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Males and females, age >= 18 years
• Clinical site A will include patients with confirmed diagnosis of metastatic melanoma (including those with brain metastases) receiving first line treatment with combination nivolumab and ipilimumab or single agent ipilimumab, nivolumab, pembrolizumab
• Clinical site B will include patients with confirmed diagnosis of metastatic renal cell carcinoma (RCC) (including those with brain metastases) receiving first line treatment with combination nivolumab and ipilimumab or single agent PD-1 inhibitor (e.g., nivolumab, pembrolizumab)
• Scheduled for imaging every 6 to 12 weeks for metastatic melanoma (MM) and mRCC as is standard of care per National Comprehensive Cancer Network (NCCN) guidelines
• Able to read, understand, and provide written informed consent
• Willing to provide stool specimen for research studies as outlined in the timeline
• Willing to participate in a ketogenic diet (KD)

Exclusion Criteria:

• Individuals < 18 years of age
• Unable or unwilling to provide consent
• Patients with type 1 diabetes mellitus or type 2 diabetes using insulin
• Patients who are clinically underweight (body mass index [BMI] < 18.5) at the start of treatment
• 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 >=5 years)
• Currently consuming a low-carbohydrate (< 130 g/day) or ketogenic diet or done so in the last 6-months
• Women who are known to be pregnant are excluded. However no additional pregnancy testing out of what would be recommended prior to initiating anti-cancer therapy will be performed solely for this study
• Patients currently participating in an interventional or therapeutic clinical trial involving the use of active anti-cancer therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (Ketogenic diet); Patients undergo a ketogenic dietary intervention with personalized coaching from a dietician about the KD, which includes extensive educational and ongoing support on the KD and continuous ketone monitoring by talking to a dietician directly, with the ability to text a dietician at any time and expect a response within 12 hours over 24weeks. Patients also undergo daily blood glucose and ketone monitoring, undergo CT, undergo blood sample collection and may undergo stool sample collection on the study.	Other: Questionnaire Administration; Ancillary studies; Procedure: Biospecimen Collection; Undergo blood and stool sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Computed Tomography; Under CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Other: Dietary Intervention; Undergo ketogenic diet; Other Names: Dietary Modification; intervention, dietary; Nutrition Intervention; Nutrition Interventions; Nutritional Interventions; Other: Educational Activity; Receive coaching support; Other: Glucose Measurement; Undergo blood glucose testing; Other Names: Glucose; GLUC; Other: Ketone Measurement; Undergo ketone measurement; Other Names: Ketones
Active Comparator: Arm II (usual caare); Patients follow a standard of care diet on the study.	Other: Best Practice; Undergo standard of care diet; Other Names: standard of care; standard therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Will be assessed by immune-related adverse events (irAEs), serious adverse events (SAEs), Treatment Emergent Adverse Events (TEAEs), clinical laboratory, vital signs, physical examinations. Will be monitored during study visits and telephone calls using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0, which also includes irAEs. Grade 3, 4 and 5 toxicities will be reported as adverse events.	Up to 1 year
Adherence (feasibility measure)	Adherence will be defined as > 80% of days in ketosis and compliant as collecting all gut microbiome specimens. Diet adherence and progress will be assessed daily using at-home whole capillary blood glucose and continuous ketone monitoring devices	Up to 1 year

Collaborators and Investigators

• Sponsor: Ohio State University Comprehensive Cancer Center
• Investigators: Principal Investigator: Marium Husain, MD, MPH, Ohio State University Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• The Jamesline

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: April 25, 2024
• First Submitted That Met QC Criteria: April 25, 2024
• First Posted (Actual): April 30, 2024

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Skin Diseases; Urologic Neoplasms; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Kidney Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Carcinoma, Renal Cell; Melanoma; Health Services Administration; Health Care Quality, Access, and Evaluation; Organic Chemicals; Investigative Techniques; Therapeutics; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Quality of Health Care; Carbohydrates; Quality Indicators, Health Care; Nutrition Therapy; Sugars; Guidelines as Topic; Quality Assurance, Health Care; Hexoses; Monosaccharides; Standard of Care; Specimen Handling; Diet Therapy; Practice Guidelines as Topic; Glucose; Ketones
• Other Study ID Numbers: OSU-21335; NCI-2024-01894 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No