Effect of Meal Timing During Cancer Treatment in Patients in Alaska: A Randomized Clinical Trial

Overview

The goal of this clinical trial is to test meal-timing as a novel and sustainable interventional approach during cancer treatment to improve therapeutic response and metabolic health in an understudied population. This clinical trial will enroll patients with rectal or breast cancer receiving neoadjuvant treatment at the Alaska Native Medical Center (ANMC), which is part of the Alaska Native Tribal Health Consortium (ANTHC). A promising strategy for improving the efficacy of anticancer treatments and reducing associated toxicities involves combining treatment with fasting regimens. In pre-clinical and clinical studies, various forms of fasting have been shown to induce tumor regression and improve long-term survival. According to the differential stress sensitization theory, fasting is thought to sensitize tumor cells to the cytotoxic effects of chemotherapy and radiation, while protecting healthy cells by increasing stress resistance. While healthy cells slow their growth and become more stress resistant in response to fasting, cancer cells cannot survive in nutrient-deficient environments; although the underlying mechanisms are not fully understood. However, extended water-only fasting can be challenging for patients and poses undue health risks. Intermittent fasting, and specifically time-restricted eating (TRE), may offer a viable alternative. TRE involves eating within a shorter window (e.g., 8 hours) and fasting for the remainder of the day but involves no other dietary restrictions. Because of its simplicity, TRE may be more sustainable than other fasting regimens. TRE also improves several cardio-metabolic endpoints, including insulin sensitivity, which may also be beneficial during anticancer treatments.

Detailed description

Participants will be randomized to one of two groups:

1. Time-restricted eating (TRE) (8-hour daily eating period, starting 1-3 hours after waking up), OR 2. A control group defined as a ≥12-hour daily eating period.

Participants are assigned to either TRE (8-hour daily eating period, starting 1-3 hours after waking up) or a control group defined as a ≥12-hour daily eating period. Their randomized meal assignment arm begins no later than 1-2 week after they begin cancer treatment and ends at end of treatment (resection if indicated). This is a period of approximately 6 months.

During this time, participants will be asked to record the time they started and finished eating every day. Electronic reminders and weekly calls to the participants will be made by study staff who maintain records of patient's meal timing. Researchers will time the TRE schedules relative to sleep time (not time of day), which is a reasonable proxy for circadian time. The control group was designed to mimic typical eating habits in the U.S., as data from NHANES suggest that the median American eats over a 12.5-hour period each day. Aside from these general prescriptions, no set number of snacks, meals, or calories will be prescribed. Instead, researchers will measure how TRE affects self-reported mealtimes, meal frequency, and food intake through a combination of daily adherence surveys, 3-day food records and continuous glucose monitoring (CGM).

Participants will receive weekly one-on-one nutrition counseling during the first month and then monthly counseling sessions thereafter. Participants will complete questionnaires at intake and subsequent follow-up assessments. Blood and stool samples will also be collected from participants throughout the study.

Interventions

• Behavioral Time-restricted eating
  Participate in time-restricted eating plan
• Other Questionnaire Administration
  Complete questionnaire
• Procedure Biospecimen Collection
  Undergo collection of blood and stool
• Behavioral Health coaching
  Receive nutrition counseling

Primary outcome measures

• Pathological Complete Response (pCR) rate [Time frame: At completion of neoadjuvant treatment (3-6 months)]
• Treatment-related toxicity [Time frame: From enrollment until completion of neoadjuvant or adjuvant treatment (3-8 months)]
• Treatment Delivery (RDI and Completion) [Time frame: From enrollment until completion of neoadjuvant or adjuvant treatment (3-8 months)]

Secondary outcome measures (10)

• Clinical Complete Response (cCR) [Time frame: At completion of neoadjuvant treatment (3-6 months)]
• Tumor volume [Time frame: From baseline to surgery (3-6 months)]
• Objective response rate (ORR) [Time frame: At the time of surgery following neoadjuvant treatment completion (3-6 months)]
• Neoadjuvant rectal (NAR) score [Time frame: At completion of neoadjuvant treatment for rectal cancer (3-6 months)]
• Provider-reported adverse events [Time frame: From enrollment until completion of neoadjuvant or adjuvant treatment (3-8 months)]
• Health-related quality of life (HR-QOL) [Time frame: From enrollment until completion of neoadjuvant or adjuvant treatment (3-8 months)]
• Adherence [Time frame: From enrollment until completion of study participation (3-8 months)]
• Progression-free survival (PFS) [Time frame: 12- and 24 months post completion of neoadjuvant treatment and surgery or adjuvant treatment.]
• Relapse-free survival (RFS) [Time frame: 12- and 24 months post completion of neoadjuvant treatment and surgery or adjuvant treatment.]
• Overall survival (OS) [Time frame: 12- and 24 months post completion of neoadjuvant treatment and surgery or adjuvant treatment.]

Eligibility criteria

Inclusion criteria

• Male or female
• Self-identify as Alaska Native or American Indian person and eligible for care at the ANMC
• Age≥21 years
• Histologically confirmed rectal cancer stage II, III, or IV (if curative) per AJCC criteria (neoadjuvant)
• Histologically confirmed HER2+ or triple negative breast cancer stage I, II, or III, per AJCC criteria (neoadjuvant)
• Histologically or cytologically confirmed solid tumor (adjuvant)
• BMI≥18.5 kg/m2
• Plan to receive neoadjuvant or adjuvant therapy
• Planned duration of neoadjuvant or systemic adjuvant therapy for >3 months to allow sufficient time to assess impact of intervention
• Must have capacity to give informed consent
• Willing and able to adhere to the assessments, visit schedules, prohibitions, and restrictions
• Has completed ≤ 4 weeks of neoadjuvant or adjuvant treatment prior to study enrollment
• Score of < 4 on U.S. Household Food Security Survey Module: Six-Item Short Form OR if score >5, have clearance from dietitian

Exclusion criteria

• History of cytotoxic chemotherapy ≤12 months prior to rectal or breast cancer diagnosis (neoadjuvant)
• Allergic reaction to any of the treatment agents
• Any prior pelvic radiotherapy
• Active second malignancy (exceptions: non-melanoma skin cancers or cervical carcinoma in situ adequately treated) requiring systemic therapy
• 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
• Unstable psychiatric, sleep, or circadian conditions (common conditions such as sleep apnea and depression are acceptable as long as they are stabilized and not rapidly worsening)
• Pregnant or breastfeeding
• Currently perform overnight shift work >1 day/week
• Strictly adhering to a <10-hour eating window on most days
• Severe psychiatric, cognitive, or substance misuse disorders or social conditions that would interfere with adherence to study procedures.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Other

Study locations

United States · 1 center

• Alaska Native Medical Center (ANMC) — Anchorage

Identifiers

NCT: NCT06802172 · RG1124486 · 1P50CA285275-01A1 · 2111923-7

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗