R01CA258222

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

Combining fasting with chemotherapy can cause complete tumor regression in animal models. Acute fasting is thought to sensitize tumor cells to the cytotoxic effects of chemotherapy and radiation, while protecting healthy cells by increasing stress resistance—a phenomenon known as the Differential Stress Sensitization Theory. However, the potential risks of extended caloric restriction hamper clinical implementation.

Time-restricted eating (TRE) is a promising alternative, which involves eating within a period of 10 hours or less, followed by fasting for at least 14 hours daily. Because of its simplicity, TRE may be more sustainable. Moreover, our pilot data suggest that TRE has several anti-cancer effects: it decreases IGF-1 levels, reduces oxidative stress, upregulates antioxidant defenses, and enhances autophagy.

We propose to conduct the first clinical trial of TRE in cancer patients undergoing active treatment, as well as the largest randomized controlled trial of any form of intermittent fasting in cancer patients. We will focus on rectal cancer because it is one of only a couple cancers where tumor size and characteristics can be measured before and after treatment.

We will enroll 300 newly diagnosed localized rectal cancer patients (Stage II-III) aged ≥18 (BMI ≥ 18.5 kg/m²). All participants will receive the standard of care during oncological treatment at Cedars-Sinai Medical Cancer (Los Angeles, CA) or the University of Alabama O'Neal Comprehensive Cancer Center (Birmingham, AL) and be randomized to one of two eating schedules: (1) Control Schedule: 12-hour or longer daily eating period; (2) TRE: 8-hour daily eating period (16 hours of daily fasting). Participants will be counseled to maintain their weight.

All endpoints will be measured at least three times: at diagnosis prior to the onset of chemoradiation (baseline), after chemoradiation treatment, and at tumor resection (post-intervention). Our primary aim is to determine how TRE affects clinical outcomes, including treatment-related adverse effects (toxicity index based on CTCAE V.5), patient-reported outcomes (PRO-CTCAE) and quality of life (EORTC QLQ-C30), and clinical (CCR) and pathological (PCR) complete response rates.

Aim 2 tests the Differential Stress Sensitization Theory—the first complete test of this theory in humans. We test whether TRE acts through the IGF-1 pathway to increase stress resistance in healthy cells (DNA damage and antioxidant defenses as measured by gamma-H2AX and total antioxidant capacity, respectively) and enhance tumor cell death (apoptosis and autophagy as measured by activated caspase-3 and LC3-I/LC3-II, respectively).

Aim 3 compares longitudinal changes in mood, social functioning, sleep, diet, and daily physical activity across intervention arms (control vs. TRE) and explores how these changes interact with intervention arms to predict clinical outcomes. We expect this innovative trial will help improve cancer treatment outcomes and reshape the standard of care for cancer patients.

Cedars-Sinai Medical Center

TO IDENTIFY CANCER RISKS AND RISK REDUCTION STRATEGIES, TO IDENTIFY FACTORS THAT CAUSE CANCER IN HUMANS, AND TO DISCOVER AND DEVELOP MECHANISMS FOR CANCER PREVENTION AND PREVENTIVE INTERVENTIONS IN HUMANS. RESEARCH PROGRAMS INCLUDE: (1) CHEMICAL, PHYSICAL AND MOLECULAR CARCINOGENESIS, (2) SCREENING, EARLY DETECTION AND RISK ASSESSMENT, INCLUDING BIOMARKER DISCOVERY, DEVELOPMENT AND VALIDATION, (3) EPIDEMIOLOGY, (4) NUTRITION AND BIOACTIVE FOOD COMPONENTS, (5) IMMUNOLOGY AND VACCINES, (6) FIELD STUDIES AND STATISTICS, (7) CANCER CHEMOPREVENTION AND INTERCEPTION, (8) PRE-CLINICAL AND CLINICAL AGENT DEVELOPMENT, (9) ORGAN SITE STUDIES AND CLINICAL TRIALS, (10) HEALTH-RELATED QUALITY OF LIFE AND PATIENT-CENTERED OUTCOMES, AND (11) SUPPORTIVE CARE AND MANAGEMENT OF SYMPTOMS AND TOXICITIES. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO STIMULATE TECHNICAL INNOVATION, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY WOMEN AND SOCIALLY/ECONOMICALLY DISADVANTAGED PERSONS. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING, AND FOSTER PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY WOMEN AND SOCIALLY/ECONOMICALLY DISADVANTAGED PERSONS.

93.393 - Cancer Cause and Prevention Research

National Cancer Institute (NCI) [HHS - NIH]

Los Angeles, California 900481804 United States

Single Zip Code

Research Answers to National Cancer Institute's (NCI) Provocative Questions (R01 Clinical Trial Optional) (RFA-CA-20-004)

Amendment Since initial award the total obligations have increased 429% from $779,477 to $4,123,295.