Time Restricted Eating (TRE) in Metastatic Head and Neck Squamous Cell Cancer (mHNSCC) or Unresectable or Metastatic Renal Cell Carcinoma (RCC)

Phase 2, Single Arm Study to Evaluate the Efficacy of Time Restricted Eating (TRE) on Immunotherapy Treatment Outcomes in Patients With Metastatic Head and Neck Squamous Cell Cancer (mHNSCC) or Unresectable or Metastatic Renal Cell Carcinoma (RCC)

The purpose of this study is to evaluate whether Time Restricted Eating (TRE) can improve responses in participants with metastatic head and neck squamous cell cancer (mHNSCC) or unresectable/metastatic renal cell carcinoma (RCC) receiving Immune Checkpoint Blockers (ICB) by changing the gut microbiome (the bacteria and other microorganisms living in individual's bodies). A particular focus of this study is to compare the outcomes of African American participants when compared to the rest of the participant population. TRE is a form of intermittent fasting where food and drink intake is limited to a specific time window during the day. The information learned from this study may help researchers develop new strategies to improve outcomes in patients with mHNSCC and RCC in the future.

Participants will be asked to complete a dietary survey at baseline and week 9 and provide a baseline stool and blood sample. Two weeks before beginning ICB and after participants completed the baseline assessments, they will begin TRE. TRE will be defined as limiting food and drink intake to a 10 hour window during each day and fasting for 14 hours at night. Participants will be asked to complete a daily food log to document the times they eat and drink. On day 1 of ICB and weeks 3, 6, 9, 26, and 52 after ICB, participants will be asked to collect a blood sample and a toxicity assessment will be performed. On day 1 of ICB and weeks 9, 26, and 52 of ICB, participants will be asked to provide a stool sample. Participants will also undergo tumor imaging throughout the study as part of their standard of care assessments. If a participant's disease progresses after ICB, they will repeat all study assessments and be withdrawn from the study.

Study Overview

• Status: Withdrawn
• Conditions: Metastatic Renal Cell Carcinoma; Unresectable Renal Cell Carcinoma; Metastatic Head-and-neck Squamous-cell Carcinoma
• Intervention / Treatment: Behavioral: Time restricted eating (TRE)

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

HNSCC Cohort

Inclusion Criteria:

1. Histologically or cytologically confirmed recurrent/metastatic head and neck squamous cell cancer that is not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy) and initiating standard of care immune checkpoint blocker- (Nivolumab, pembrolizumab, Atezolizumab, Avelumab or Durvalumab with or without chemotherapy), for the first time.
2. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as outlined in RECIST version 1.1.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
4. Age ≥18 years, able to understand and voluntarily consent.

Exclusion Criteria:

1. BMI < 18.5.
2. Diabetes mellitus, pregnancy, any eating disorder including anorexia nervosa or bulimia.
3. Ongoing or active infection requiring iv antibiotics, autoimmune disease requiring systemic steroids greater than prednisone 60 mg equivalent, symptomatic congestive heart failure, unstable angina pectoris, insulin use, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
4. Patients who have known leptomeningeal metastases or untreated or symptomatic brain metastases. Eligible patients must be neurologically asymptomatic and not requiring steroids.
5. Has received prior therapy with any anti-PD-1, anti-PDL-1 in a metastatic setting.
6. Patients for whom fasting is medically contraindicated

RCC Cohort

Inclusion Criteria:

1. Histologically or cytologically confirmed unresectable/metastatic clear cell renal cell carcinoma that is not amenable to local therapy with curative intent (surgery, radiation therapy, cryoablation, etc.,) and initiating standard of care systemic therapy consisting of immune checkpoint blockade (e.g. ipilimumab/nivolumab, cabozantinib/nivolumab, lenvatinib/pembrolizumab, or axitinib/pembrolizumab) for the first time.
2. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as outlined in RECIST version 1.1.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
4. Age ≥18 years, able to understand and voluntarily consent.

Exclusion Criteria:

1. BMI < 18.5.
2. Diabetes mellitus, pregnancy, any eating disorder including anorexia nervosa or bulimia.
3. Ongoing or active infection requiring iv antibiotics, autoimmune disease requiring systemic steroids greater than prednisone 60 mg equivalent, symptomatic congestive heart failure, unstable angina pectoris, insulin use, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
4. Patients who have known leptomeningeal metastases or untreated or symptomatic brain metastases. Eligible patients must be neurologically asymptomatic and not requiring steroids.
5. Has received prior therapy with any anti-PD-1, anti-PDL-1
6. Patients for whom fasting is medically contraindicated

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Time Restricted Eating (TRE) for mHNSCC participants	Behavioral: Time restricted eating (TRE); TRE is defined as limiting daily food intake to 10 hour period with a nightly fasting period of 14 hours.
Experimental: Time Restricted Eating (TRE) for RCC participants	Behavioral: Time restricted eating (TRE); TRE is defined as limiting daily food intake to 10 hour period with a nightly fasting period of 14 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time restricted eating (TRE) associated change in gut microbiome	Microbiome changes in stool	Baseline, Day 1, Week 9, Week 26 and Week 52
Time restricted eating (TRE) associated change in metabolome	Metabolomics in blood	Baseline, Day 1, Week 9, Week 26 and Week 52
Time restricted eating (TRE) associated change in IGF1	IGF1 level in blood	Baseline, Day 1, Week 9, Week 26 and Week 52
Time restricted eating (TRE) associated change in immune repertoire	Comprehensive analysis of effector T cells and suppressor T cell populations in PBMC, plasma cytokines will be carried out	Baseline, Day 1, Week 9, Week 26 and Week 52
Response to immune checkpoint blocker (ICB) at first response assessment	Radiographic response as per RECIST 1.1	Week 9
Median progression free survival (PFS) for HNSCC cohort only	Time from enrollment to radiographic disease progression as per RECIST 1.1 or death from any cause	1 Year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year immune related adverse events (irAE) rate	1 year rate of irAE, as per CTCAE v.5	1 Year
Feasibility of Time restricted eating (TRE) in African American HNSCC participants on immune checkpoint blocker (ICB)	Number of African American participants who were compliant, which is defined as 14 hr TRE daily for 5 days per week, for 9 out of first 12 weeks (70%)	Through Week 52
1-year immune related adverse events (irAE) rate in African American participants	1 year rate of irAE, as per CTCAE v.5 in African American participants	1 year
Median progression free survival (PFS) for RCC cohort only	Time from enrollment to radiographic disease progression as per RECIST 1.1 or death from any cause	1 Year

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Daniel George, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: September 17, 2024
• First Submitted That Met QC Criteria: September 17, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): December 19, 2025
• Last Update Submitted That Met QC Criteria: December 15, 2025
• Last Verified: December 1, 2025

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; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Urologic Neoplasms; Carcinoma; Kidney Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Renal Cell
• Other Study ID Numbers: Pro00115641

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