Time-Restricted Eating and Cancer: Clinical Outcomes, Mechanisms, and Moderators

NCT ID: NCT04722341

Last Updated: 2025-12-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 175 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-01
• Study Completion Date: 2026-12-31

Brief Summary

The purpose of this study is to test whether the timing of meals can improve treatment adverse events, influence tumor biology and alter a person's mood and behaviors.

Detailed Description

Combining fasting with chemotherapy is known to cause complete tumor regression and long-term survival in animal models. According to the Differential Stress Sensitization (DSS) theory, acute fasting sensitizes tumor cells to the cytotoxic effects of chemotherapy and radiation, while protecting healthy cells by increasing stress resistance. These effects are believed to be largely mediated via the Insulin-like Growth Factor (IGF-1) pathway. However, extended fasting can be challenging for patients and poses undue health risks. A number of alternative intermittent fasting regimens have been proposed to overcome the challenges of prolonged caloric restriction. One promising approach is time-restricted eating (TRE), which involves eating within a period of 10 hours or less, followed by fasting for at least 14 hours daily. TRE does not involve extended caloric restriction, and because of its simplicity, it may be more sustainable than other fasting regimens. TRE improves several cardiometabolic endpoints independent of calorie restriction in both animals and humans, including insulin sensitivity, blood pressure, fat oxidation, and hunger. Our team's pilot and feasibility trials suggest that TRE may also have anti-cancer effects: it decreases IGF-1 levels, reduces oxidative stress, upregulates antioxidant defenses, and enhances autophagy. Moreover, our data suggest TRE is sustainable, as participants were adherent 6.0 plus or minus 0.8 days/week over a 14-week period. These findings lead to the following provocative question: Can TRE reduce treatment-related toxicity, induce tumor regression, and improve both patient-reported and clinical outcomes? We propose to conduct the largest randomized controlled trial of any form of intermittent fasting in patients undergoing cancer treatment. We focus on patients with localized rectal or breast cancer because it is one of the few treatment paradigms in which tumor characteristics can be measured before and after chemoradiation therapy.

Conditions

Colorectal Cancer; Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Time-Restricted Eating (TRE)

8-hour daily eating period. Participants eating window must start within 2 hours of waking up and no later than 9 am.

Group Type: EXPERIMENTAL

Time-Restricted Eating (TRE)

Intervention Type: BEHAVIORAL

8-hour daily eating period, starting 1-3 hours after waking up

Control

More than equal to a 12-hour daily eating period

Group Type: ACTIVE_COMPARATOR

Control

Intervention Type: BEHAVIORAL

More than equal to a 12-hour daily eating period

Interventions

Time-Restricted Eating (TRE)

8-hour daily eating period, starting 1-3 hours after waking up

Intervention Type: BEHAVIORAL

Control

More than equal to a 12-hour daily eating period

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Any sex/gender of any ethnic/racial background
• Age greater than or equal to 18 years
• Histologically-confirmed rectal cancer stage II, III, or IV (if curative) or human epidermal growth factor receptor 2-positive (HER2+) or triple negative breast cancer stage I, II, or III (only if definitive intent) per American Joint Committee on Cancer (AJCC) criteria
• BMI 18.5 kg/m2 or greater
• Receiving either neoadjuvant therapy with curative intent (breast cancer patients) or total neoadjuvant therapy with a 5-fluorouracil-based regimen and curative intent (rectal cancer patients)
• Has completed ≤ 4 weeks of neoadjuvant treatment prior to study enrollment
• Willing and able to adhere to the assessments, visit schedules, prohibitions, and restrictions

Exclusion Criteria

• History of cytotoxic chemotherapy less than or equal to 12 months prior to rectal or breast cancer diagnosis
• Allergic reaction to any of the treatment agents
• Any prior pelvic radiotherapy
• Currently active second malignancy other than non-melanoma skin cancers or cervical carcinoma in situ
• History of GI perforation ≤12 months prior to enrollment
• History of predisposing colonic or small bowel disorders with severe or rapidly worsening symptoms (not related to current cancer symptoms)
• Receiving any parenteral nutrition or enteral (tube) feeding or using similar nutritional supplement during the study period
• History of uncontrolled congestive heart failure defined as ew York Heart Association Class (NYHA) Class III or greater
• Pre-existing grade ≥3 neuropathy
• Currently participating in or has participated in a study of an investigational agent or investigational device ≤4 weeks of the first dose of treatment
• Pregnant or breastfeeding
• Currently perform overnight shift work more than one day/week on average
• Strictly adhering to a <10-hour eating window on most days
• Known psychiatric or substance abuse disorders that would interfere with adhering to the requirements of the trial
• Medical condition or laboratory abnormality that could impact participant safety or data validity, in the opinion of the medical investigators.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: collaborator

Harvard University

OTHER

Sponsor Role: collaborator

Cedars-Sinai Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Sarah Salvy

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status: RECRUITING

Cedars-Sinai Medical Center

West Hollywood, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Nathalie Nguyen, MPH

Role: CONTACT

nathalie.nguyen@cshs.org

310.423.4209

Facility Contacts

Courtney M Peterson, PhD

Role: primary

Nathalie Nguyen, MPH

Role: primary

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1R01CA258222-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

15494

Identifier Type: -

Identifier Source: org_study_id