Clinical trial NCT04722341: Time-Restricted Eating and Cancer: Clinical Outcomes, Mechanisms, and Moderators
Official title: Time-Restricted Eating and Cancer: Clinical Outcomes, Mechanisms, and Moderators
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Colorectal Cancer
Breast Cancer
Lead sponsor: Cedars-Sinai Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: University of Alabama at Birmingham
First posted: 2021-01-25
Enrollment: 175
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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) per AJCC criteria
* Histologically confirmed HER2+ or triple negative breast cancer stage I, II, III, or IV (only if definitive intent) per AJCC criteria
* BMI 18.5 kg/m2 or greater
* Will receive neoadjuvant therapy
* 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 CHF defined as 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

Primary outcomes:
measure: Treatment Related Toxicities
timeFrame: at end of 6 month intervention
measure: Patient-reported outcomes (PROs)
timeFrame: at end of 6 month intervention
Secondary outcomes:
measure: Signaling
timeFrame: at end of 6 month intervention
measure: Mood
timeFrame: at end of 6 month intervention
measure: Psychosocial Functioning
timeFrame: at end of 6 month intervention
measure: Dietary Intake
timeFrame: at end of 6 month intervention
measure: Physical Activity
timeFrame: at end of 6 month intervention
measure: Sleep
timeFrame: at end of 6 month intervention
Other outcomes:
Locations:
city: West Hollywood
country: United States
facility: Cedars-Sinai Medical Center
state: California
Study officials:
References: