Time Restricted Eating for Head and Neck Squamous Cell Carcinoma

Overseen By Julia Hurrelbrink, BA, BSN, RN

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Duke University

Must be taking: Immune checkpoint blockers

Must not be taking: Systemic steroids, Insulin

Disqualifiers: Diabetes, Pregnancy, Eating disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 52 weeks

115 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if Time Restricted Eating (TRE)—a type of intermittent fasting with a 10-hour daily eating window—can enhance the response to immune checkpoint blockers in certain cancer patients. The focus is on metastatic head and neck squamous cell cancer and advanced renal cell carcinoma. Researchers are examining how TRE may influence the gut microbiome and improve treatment outcomes, particularly for African American participants. Suitable candidates for this trial include those with one of these cancers who are beginning immune therapy for the first time and can adhere to the TRE schedule. As an unphased trial, this study provides a unique opportunity to explore innovative treatment strategies that could improve cancer therapy responses.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on systemic steroids greater than Prednisone 60 mg or insulin, you may not be eligible to participate.

What prior data suggests that Time Restricted Eating is safe for participants with mHNSCC and RCC?

Research has shown that time-restricted eating (TRE) is generally safe for people with head and neck squamous cell carcinoma (HNSCC). One study found that combining TRE with immune checkpoint blockers (ICB), a type of cancer treatment, was safe and practical, allowing most people to follow the eating schedule without major side effects.

For renal cell carcinoma (RCC), early studies indicate that TRE is safe and acceptable. It might also improve the quality of life for people with cancer. While more research is needed, TRE does not seem to cause harm and is well-tolerated by most participants.

In summary, TRE appears safe for people with both HNSCC and RCC. It involves fasting for 14 hours at night, which most participants can manage without issues. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Time Restricted Eating (TRE) for head and neck squamous cell carcinoma because it offers a completely different approach from traditional treatments like surgery, radiation, and chemotherapy. Unlike these standard options, which focus on directly attacking cancer cells, TRE involves adjusting the timing of food intake to potentially enhance the body’s natural cancer-fighting mechanisms. This method could improve patient outcomes by optimizing metabolism and reducing inflammation, all without the side effects associated with conventional treatments. Additionally, TRE is non-invasive and could be more easily integrated into patients' daily lives, making it an attractive complementary strategy in cancer care.

What evidence suggests that Time Restricted Eating might be an effective treatment for metastatic head and neck squamous cell cancer and renal cell carcinoma?

Research suggests that Time Restricted Eating (TRE) might benefit individuals with advanced head and neck cancer. In this trial, participants with metastatic head and neck squamous cell carcinoma (mHNSCC) will adhere to a TRE regimen. Studies have found that TRE can extend the time patients live without cancer progression by influencing gut bacteria, potentially enhancing cancer treatment effectiveness. Lab experiments have shown that fasting increases chemotherapy's impact on cancer cells. Participants with renal cell carcinoma (RCC) will also follow a TRE regimen. For kidney cancer, TRE has shown promise in reducing tumor activity in animal studies, though its effect on specific cancer treatments remains unclear. Overall, TRE might improve the body's response to cancer treatments. ^{1 3 4 6 7}

Who Is on the Research Team?

Daniel George, MD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with metastatic head and neck squamous cell cancer who are about to start standard immune checkpoint blocker therapy. They should be relatively healthy (ECOG status of 0 or 1) and have a measurable tumor size according to RECIST criteria.

Inclusion Criteria

My head and neck cancer has returned or spread and cannot be cured with surgery or radiation, and I am starting immunotherapy.

I am fully active or can carry out light work.

Patients must have measurable disease as outlined in RECIST version 1.1

Exclusion Criteria

I have diabetes, am pregnant, or have an eating disorder like anorexia or bulimia.

Patients for whom fasting is medically contraindicated

BMI < 18.5

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment

Participants begin Time Restricted Eating (TRE) two weeks before starting Immune Checkpoint Blockers (ICB) and complete baseline assessments

2 weeks

1 visit (in-person)

Treatment

Participants receive Immune Checkpoint Blockers (ICB) and continue Time Restricted Eating (TRE) with regular blood and stool sample collections and toxicity assessments

52 weeks

Visits at Day 1, Weeks 3, 6, 9, 26, and 52

Follow-up

Participants are monitored for safety and effectiveness after treatment, including progression-free survival and immune-related adverse events

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Time Restricted Eating (TRE)

Trial Overview The study tests if Time Restricted Eating (TRE), which limits eating and drinking to a 10-hour window daily, can improve treatment responses in mHNSCC patients by altering gut bacteria. It also compares outcomes between African American participants and others.

How Is the Trial Designed?

Group I: Time Restricted Eating (TRE) for mHNSCC participants Experimental Treatment 1 Intervention

Group II: Time Restricted Eating (TRE) for RCC participants Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Published Research Related to This Trial

In a study of 20 head and neck cancer patients, most experienced a negative energy balance both at the start of and after radiotherapy, indicating that their energy expenditure exceeded their energy intake.

The lack of significant changes in energy intake and expenditure during treatment highlights the critical need for nutritional support to prevent involuntary weight loss in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An explorative study on energy balance in patients with head and neck cancer. Einarsson, S., Laurell, G., Tiblom Ehrsson, Y.[2021]

In a study of 468 newly diagnosed head and neck squamous cell carcinoma (HNSCC) patients, higher adherence to the AHEI-2010 dietary index was strongly associated with reduced all-cause and cancer-specific mortality, suggesting that diet quality can significantly impact survival outcomes.

The research indicates that following a plant-based low-carbohydrate diet may also improve prognosis for HNSCC patients, highlighting the potential role of dietary patterns in cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence to a priori-Defined Diet Quality Indices Throughout the Early Disease Course Is Associated With Survival in Head and Neck Cancer Survivors: An Application Involving Marginal Structural Models. Maino Vieytes, CA., Rodriguez-Zas, SL., Madak-Erdogan, Z., et al.[2022]

In a study of 62 patients with head and neck cancer receiving home enteral nutrition (HEN) via feeding tubes, those who started HEN before radiotherapy maintained their Body Mass Index (BMI) and did not experience weight loss during treatment.

The main reason for initiating enteral nutrition was dysphagia, and the most common feeding method was through naso-gastric tubes, with patients receiving an average of 1,629 kcal/day from a polymeric hypercaloric diet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Head and neck cancer patients included at home enteral nutrition by tube]. Cots Seignot, I., Cárdenas Lagranja, G., Puiggròs Llop, C., et al.[2013]

A systematic review of 10 randomized controlled trials involving 585 patients found that interventions like dietary counseling, megestrol acetate, and prophylactic enteral tube feeding can help maintain or improve nutritional status in patients with head and neck squamous cell carcinoma undergoing radiotherapy.

The review highlights a significant gap in research, as the studies were limited in number and quality, and many potentially effective nutritional interventions have not been tested in combination or compared directly, indicating a need for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutritional support for head and neck cancer patients receiving radiotherapy: a systematic review. Garg, S., Yoo, J., Winquist, E.[2022]

Refeeding syndrome is a serious and potentially fatal condition that can occur in head and neck cancer patients after a period of starvation, characterized by dangerous electrolyte shifts and metabolic complications.

To prevent refeeding syndrome, it is crucial to start refeeding at a low rate of 10 kcal/kg per day for at-risk patients, particularly those with dysphagia, and to provide vitamin supplements during the process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Refeeding syndrome--awareness, prevention and management. Mehanna, H., Nankivell, PC., Moledina, J., et al.[2021]

In a study of 110 patients with head and neck cancer undergoing treatment, the need for enteral nutrition (EN) significantly increased due to treatment-related toxicities, particularly from week 3 to 4, highlighting the importance of monitoring these toxicities.

Patients experiencing more severe dysphagia (grade 2-3) were less likely to stop EN, suggesting that assessing acute toxicities can help guide timely EN initiation and predict its duration, potentially preventing nutritional decline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enteral nutrition support and treatment toxicities in patients with head and neck cancer receiving definitive or adjuvant helical intensity-modulated radiotherapy with concurrent chemotherapy. Blake, CL., Brown, TE., Pelecanos, A., et al.[2023]

Head and neck cancer patients are at high risk for malnutrition and refeeding syndrome (RFS), which can lead to serious fluid and electrolyte imbalances if not managed properly.

Early nutritional assessment and intervention are essential for preventing RFS in these patients, highlighting the need for a multidisciplinary approach to care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Malnutrition and refeeding syndrome prevention in head and neck cancer patients: from theory to clinical application. Kaderbay, A., Atallah, I., Fontaine, E., et al.[2021]

About one third of the 120 patients with oral and oropharyngeal cancer experienced major food restrictions, significantly impacting their nutrition during treatment.

Factors such as larger tumor size, location of the tumor, radiotherapy, loss of tongue mobility, and loss of teeth were identified as significant predictors of food restrictions, highlighting the need for targeted nutritional interventions in patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Food restrictions of patients who are undergoing treatment for oral and oropharyngeal cancer. da Cruz, Ede P., Toporcov, TN., Rotundo, LD., et al.[2015]

In a study of 68 head and neck cancer patients, only 12% were found to be nutritionally impaired, highlighting the need for better nutritional monitoring and intervention during and after treatment.

General practitioners (GPs) often failed to document weight loss or nutritional concerns in referral letters, indicating a gap in communication that could affect patient care and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight loss in head and neck cancer patients little noticed in general practice. van Wayenburg, CA., Rasmussen-Conrad, EL., van den Berg, MG., et al.[2010]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7957951/

Therapeutic Time-restricted Feeding Reduces Renal ... Therapeutic TRF exhibits modest anti-cancer properties but fails to improve anti-CTLA-4 immune checkpoint blockade in murine renal cancer.

2. academic.oup.com academic.oup.com/nutritionreviews/article/83/7/e1660/7745808

Clinical Impact of Time-restricted Eating on Cancer Preliminary findings suggest that TRE is feasible and acceptable by people with cancer, may have oncological benefits, and improves quality of life.

3. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/caac.21694

Intermittent fasting in the prevention and treatment of cancer Therapeutic time-restricted feeding reduces renal tumor bioluminescence in mice but fails to improve anti-CTLA-4 efficacy. Anticancer Res ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2161831322000837

Current Evidence and Directions for Intermittent Fasting ... Available data show that periodic fasting, a form of intermittent fasting, may hold potential to improve the effectiveness of chemotherapy, decrease treatment- ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10157769/

Intermittent fasting interventions to leverage metabolic and ... The metabolic and circadian rhythm mechanisms underlying the proposed benefits of intermittent fasting for the cancer population are described.

6. ar.iiarjournals.org ar.iiarjournals.org/content/40/10/5445

Therapeutic Time-restricted Feeding Reduces Renal ... Time-restricted feeding (TRF) significantly reduces primary renal tumor bioluminescence but does not alter tumor weight at sacrifice in high-fat diet-fed mice.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05114798

Time-restricted Eating Versus Daily Continuous Calorie ... Time-restricted eating, a type of intermittent fasting, has been shown in animals to impart cancer protective effects including lower body weight, decreased ...