Breast Cancer Stage I, Breast Cancer Stage II, Breast Cancer Stage III, Rectal Cancer Stage II, Rectal Cancer Stage III, Rectal Cancer Stage IV, Solid Tumor Cancer
Conditions
Keywords
Time-restricted eating, Time restricted eating, Meal timing
Brief summary
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
BEHAVIORALTime-restricted eating
Participate in time-restricted eating plan
OTHERQuestionnaire Administration
Complete questionnaire
PROCEDUREBiospecimen Collection
Undergo collection of blood and stool
BEHAVIORALHealth coaching
Receive nutrition counseling
Sponsors
Fred Hutchinson Cancer Center
National Cancer Institute (NCI)
Alaska Native Tribal Health Consortium
Alaska Native Medical Center
Cedars-Sinai Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Response (pCR) rate | At completion of neoadjuvant treatment (3-6 months) | The pCR will be defined as an absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected rectal or breast specimen and all sampled regional lymph nodes. It will be treated as a binary variable. |
| Treatment-related toxicity | From enrollment until completion of neoadjuvant or adjuvant treatment (3-8 months) | The Patient Reported Outcome-Common Terminology Criteria for Adverse Events (PRO-CTCAE v.5) measurement system will be used to measure treatment-related toxicities. The PRO-CTCAE will be administered on a weekly basis throughout the intervention and will calculate the average over all items for each time point. Surveys will be timed relative to the start of each oncologic treatment segment. |
| Treatment Delivery (RDI and Completion) | From enrollment until completion of neoadjuvant or adjuvant treatment (3-8 months) | Chemotherapy, targeted therapy, immunotherapy and/or radiation data will be abstracted to calculate relative dose intensity (RDI--delivered ÷ planned dose intensity, mg/m²/week) for each drug, expressed continuously and dichotomized at ≥85%. Regimen-level RDI will be calculated as the average across drugs or based on the dose-limiting agent. We will also calculate the proportion of participants completing all planned cycles without unplanned reductions or delays. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Complete Response (cCR) | At completion of neoadjuvant treatment (3-6 months) | A cCR will be defined as the clinical absence of residual disease on physical examination, endoscopic examination, and/or repeat MRI imaging following completion of total neoadjuvant treatment. |
| Tumor volume | From baseline to surgery (3-6 months) | Standard of care CT and MRI images will be obtained at the time of diagnosis for staging. A repeat standard of care MRI imaging may be obtained prior to surgery to assess response to neoadjuvant therapy and to guide clinical and surgical management. Researchers will obtain routine clinical restaging scans from participants and use them to estimate changes in tumor volume between the two time points. |
| Objective response rate (ORR) | At the time of surgery following neoadjuvant treatment completion (3-6 months) | The ORR is defined as the percentage of people who have a partial response (defined as a decrease in tumor volume) or a complete response to treatment between enrollment and surgery. |
| Neoadjuvant rectal (NAR) score | At completion of neoadjuvant treatment for rectal cancer (3-6 months) | The NAR score is a validated surrogate endpoint for oncologic outcomes used in rectal cancer clinical trials. It takes as input the pathologic nodal status and the clinical and pathologic T-stage. |
| Provider-reported adverse events | From enrollment until completion of neoadjuvant or adjuvant treatment (3-8 months) | As secondary measures of toxicity, researchers will collect provider-reported adverse event data. Researchers will analyze the incidence of grade 3-4 toxicities and calculate the aggregated Toxicity Index (TI). The TI accounts for the frequency and cumulative burden of all toxicities during the treatment period. |
| Health-related quality of life (HR-QOL) | From enrollment until completion of neoadjuvant or adjuvant treatment (3-8 months) | We will use the widely-used and validated European Organization for Research and Treatment of Cancer Quality of Life (QOL) core questionnaire C30 (EORTC QLQ-C30), the colorectal-cancer specific questionnaire (EORTC CR29), and the breast cancer specific questionnaire (PR\_BR23). For this study, we focus on highly prevalent rectal and breast cancer treatment-related symptoms, including fatigue, insomnia, pain and bowel-related items (stool frequency, flatulence, and fecal incontinence). |
| Adherence | From enrollment until completion of study participation (3-8 months) | Adherence will be defined as at least 70% of the daily regimen followed (for example, eating \<8 hours for 6 or more days per week on average during the 6-month treatment period). Participants will be asked to self-report their adherence using a weekly survey, which asks participants to record the time they start and finish eating each day and to document any reasons for non-adherence. |
| Progression-free survival (PFS) | 12- and 24 months post completion of neoadjuvant treatment and surgery or adjuvant treatment. | Progression-free survival (PFS) is the length of time from randomization to disease progression or death from any cause. |
| Relapse-free survival (RFS) | 12- and 24 months post completion of neoadjuvant treatment and surgery or adjuvant treatment. | Relapse-free survival (RFS) is the length of time after primary cancer treatment ends that a patient survives without any signs or symptoms of that cancer. |
| Overall survival (OS) | 12- and 24 months post completion of neoadjuvant treatment and surgery or adjuvant treatment. | Overall survival (OS) is the time from randomization to death from any cause. |
Countries
United States
Contacts
CONTACTTimothy Thomas, MD
PRINCIPAL_INVESTIGATORTimothy Thomas, MD
Alaska Native Tribal Health Consortium (ANTHC)
PRINCIPAL_INVESTIGATORJane Figueiredo, PhD, M.Sc.
Cedars-Sinai Medical Center
Outcome results
None listed