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

Cedars-Sinai Medical Center

Status

Enrolling

Conditions

Breast Cancer

Colorectal Cancer

Treatments

Behavioral: Time-Restricted Eating (TRE)

Behavioral: Control

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT04722341

1R01CA258222-01 (U.S. NIH Grant/Contract)

15494

Details and patient eligibility

About

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.

Full 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.

Enrollment

175 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.