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Trial registered on ANZCTR


Registration number
ACTRN12623000996662
Ethics application status
Approved
Date submitted
18/08/2023
Date registered
13/09/2023
Date last updated
13/09/2023
Date data sharing statement initially provided
13/09/2023
Type of registration
Prospectively registered

Titles & IDs
Public title


The FASTEX trial: Fasting mimicking diet and exercise medicine as adjuvant therapies in the treatment of patients with breast cancer.
Scientific title
A non-randomised controlled preliminary efficacy trial to test the effects of a Fasting mimicking diet and exercise medicine on achievement of pathological complete response during neoadjuvant chemotherapy in breast cancer patients (the FASTEX trial).
Secondary ID [1] 309649 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
breast cancer
 329989 0
Condition category
Condition code
Cancer 326897 326897 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will choose what group they want to be allocated at.

Arm 1: Fasting mimicking diet (FMD) group. Patients will follow a FMD (plant-based, low calories, low sugar, low protein diet), for 5 days, on chemotherapy weeks or every two weeks if chemotherapy regimen is weekly, for the duration of their chemotherapy regimen (16-20 weeks). The diet will start 2 days before the chemotherapy infusion to induce a differential stress response between normal and tumour cells and end two days after, as refeeding during this period may increase the susceptibility of healthy cells to the cytotoxic damage from chemotherapy by promoting DNA synthesis . On day 1 and day 5 the diet consists of ~900-1100 kcal with 9-15% protein, and on days 2–4 it consists of ~500-600 kcal, with 9-12% of protein. The experimental dietary regimen will be prescribed as a list of foods (e.g., cereals such as quinoa and rice, legumes, vegetables, seeds and nuts, olive or coconut oil) and drinks (water, coffee, tea, tisanes), with their allowed amount specified . Participants will also be asked to complete a food diary during each FMD cycle. Between FMD cycles, patients will be asked to follow their usual diet, encouraging them to have adequate caloric (30–40 kcal/kg weight/day) and protein intake (1.5 g protein/kg weight/day). Weight will be measured between FMD cycles; if there is a 5% or greater weight lost, calculated as (weight loss in kg / baseline weight) *100 , the diet between cycles will be reviewed and adjusted by a dietitian affiliated with the study. Compliance to the FMD will be measured for the intervention group by assessing the number of FMD cycles each patient follows (recorded in their food diaries).

Arm 2: Exercise program group. Exercise program sessions will be supervised and they will be performed at the Exercise Medicine Research Institute (EMRI) associated exercise facilities (ECU Joondalup, ECU Mount Lawley, UWA, Fiona Stanley Hospital, West Coast Health and High-Performance Lathlain). Participants will be supervised by a trained person overseen by an accredited exercise physiologist (AEP) for each exercise session over their neoadjuvant chemotherapy. Supervised sessions will be be conducted one-on-one or in small groups (up to 6 participants). The exercise intervention will consist of 100-180 min of moderate to vigorous exercise per week, comprising supervised resistance and aerobic exercise. During the weeks of chemotherapy, patients will exercise 2 days/week for 50-60 min per session (15-20 min of aerobic and 20-25 min of resistance training). During the weeks without chemotherapy treatment, patients will exercise 3 days/week for 50-60 min per session (15-20 min of aerobic and 20-25 min of resistance training). Each session will start with 5 minutes of warm-up (low-intensity aerobic exercise such as treadmill walking) and will end with a 10-minute cool-down (stretching and breathing relaxation). As participants will be exercising during neoadjuvant chemotherapy, the prescription will enable patients to autoregulate sessions, weekly and monthly exercise dosage through modifications to mode, intensity, frequency, duration and/or total volume, depending on the participant’s perceived preparedness for training at the start of each exercise session. Tolerance will be determined at the end of each exercise training session using Borg’s Rating of Perceived Exertion (RPE) 6–20 scale, with <7 corresponding to “very, very light”;7–9,“very light”;9–11,“fairly light,”11–13,“somewhat hard,”13–15,“hard,”15–17,“very hard”; and 17–20,“very, very hard”.

Resistance training

Resistance training will comprise 2 sets of 8-12 repetitions for 6-8 different strength exercises at moderate to vigorous intensity (RPE set at 11-15 on the 6-20 Borg scale) targeting the major upper and lower body muscle groups performed using body weight and equipment such as exercise machines and dumbbells. Load will be gradually increased by 5-10 % if the patient can complete more than prescribed repetitions with the correct technique. Exercises will include knee push-ups, squats, lunges, planks, leg press, leg extension, leg curl, seated calf raise, chest press, seated row, biceps curl, and triceps extension.

Aerobic training

Aerobic training will involve cardiorespiratory exercise using a variety of modes such as walking and jogging on a treadmill or cycling on a stationary ergometer. Intensity will be progressed over the 16-week period by increasing resistance or speed to elicit a target RPE of 11-15 on the 6-20 Borg scale.

Compliance to the exercise sessions will be assessed by attendance rate, determinised by the total and weekly number of exercise sessions attended versus the number of sessions prescribed, and by the adherence rate, determined by the number of sessions where the prescribed exercise are successfully completed (including volume and intensity) versus the number of sessions attended.
Intervention code [1] 326082 0
Treatment: Other
Comparator / control treatment
Arm 3: Convenience control group. Participants who do not want to follow either the FMD or the exercise program but who want still to participate in the study. These participants will only receive the neoadjuvant chemotherapy.
Control group
Active

Outcomes
Primary outcome [1] 334736 0
Pathologic stage after neoadjuvant chemotherapy: it will be assessed at the completion of chemotherapy, following surgical resection, according to the American Joint Committee on Cancer (AJCC) system. The pathologic complete response (pCR) will be determined by a pathologist following examination of tissue (breast and nodes) removed at the time of surgery. Moreover, a four-point Residual Cancer Burden (RCB) index will be also assessed from routine pathologic sections to report the pathological outcome.
Timepoint [1] 334736 0
After surgery.
Secondary outcome [1] 421907 0
Frequency and phenotype of CD8+ T cells and NK cells in blood will be measured by multicolour flow cytometry. This will be assessed as a composite outcome.
Timepoint [1] 421907 0
Secondary outcomes will be measured at baseline (before they start the neoadjuvant chemotherapy) and at the end of the interventions ( when they finish the neoadjuvant chemotherapy and before surgery).
Secondary outcome [2] 426026 0
Serum levels of IGF-1 and insulin, and cytokines IL-6, IL-7, IL-15 will be measured by enzyme-linked immunosorbent assay (ELISA). This will be assessed as a composite outcome.
Timepoint [2] 426026 0
At baseline and at the end of the interventions.
Secondary outcome [3] 426027 0
Cytotoxicity of CD8+ T cells will be analysed by enzyme-linked immunospot (ELISPOT) assay quantifying the number of IFN-gamma secreting CD8+ T cells.
Timepoint [3] 426027 0
At baseline and at the end of the interventions.
Secondary outcome [4] 426028 0
Infiltration of NK cells, CD8+ T cells, regulatory T cells and macrophages in the tumour samples by immunohistochemistry. This will be assessed as a composite outcome.
Timepoint [4] 426028 0
At baseline (diagnose biopsies) and at surgery after the neoadjuvant chemotherapy
Secondary outcome [5] 426032 0
Changes in body composition: whole body composition (whole body lean mass, fat mass and percentage of body fat) will be analysed by dual-energy X-ray absorptiometry (DXA). This will be assessed as a composite outcome.
Timepoint [5] 426032 0
At baseline and at the end of the interventions
Secondary outcome [6] 426037 0
Changes in arthrometry measures. Height and body mass will be measured using a stadiometer and a electronic scale, respectively, and body mass index (BMI) (kg/m2) will be calculated.
Timepoint [6] 426037 0
At baseline and at the end of the interventions.
Secondary outcome [7] 426040 0
Compliance: For the FMD group, compliance to the FMD will be measured for the intervention group by recording the number of FMD cycles each patient follows (recorded in their food diaries).  For the exercise group, compliance will be assessed by the attendance  and adherence rates. Attendance will be determined by the total and weekly number of exercise sessions attended versus the number of sessions prescribed. Adherence will be determined by the number of sessions where the prescribed resistance and aerobic- based exercises are successfully completed (including volume and intensity) versus the number of sessions attended. Attendance and adherence data will be collected through a training program log throughout the intervention.
Timepoint [7] 426040 0
At the end of the interventions
Secondary outcome [8] 426041 0

Acceptability of both interventions will be assessed via Likert scales and through open-ended question designed specifically for this study.
Timepoint [8] 426041 0
At the end of the interventions.
Secondary outcome [9] 426059 0
Breast cancer specific Quality of Life (QoL) will be assessed with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) BR23.
Timepoint [9] 426059 0
At baseline and at the end of the interventions.
Secondary outcome [10] 426060 0
Cancer-related fatigue will be assessed with the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue questionnaire.
Timepoint [10] 426060 0
At baseline and at the end of the interventions.
Secondary outcome [11] 426439 0
Cytotoxicity of NK cells will be measured by calcein-based killing assay against the triple negative breast cancer cell line MDA-MB 231.
Timepoint [11] 426439 0
At baseline and at the end of the interventions.

Eligibility
Key inclusion criteria
Women aged 18 years and older, diagnosed with breast cancer and scheduled for NACT.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
For FMD group, patients will be excluded if they: (i) ) have a body mass index (BMI) lower than 19 kg/m2; (ii) have impaired gastrointestinal function that may alter the digestion and absorption of nutrients (e.g., uncontrolled nausea, vomiting, diarrhoea); (iii) are taking medication that can cause hypoglycaemia (e.g., insulin for diabetes); (iv) have malnutrition (unintentional weight loss of >5% in the last 6 months); (v) if they were undertaking 300 min or more of exercise per week (vi) have an uncontrolled medical condition (other than cancer); (vii) cannot read or understand English; and (viii) are pregnant or breastfeeding.

For Exercise group: patients will be excluded if they: (i) have an acute illness or musculoskeletal, cardiovascular, or neurological disorder that could inhibit exercise participation; (ii) have an uncontrolled medical condition (other than cancer); (iii) if they were undertaking 300 min or more of exercise per week (iv) cannot read or understand English; and (v) are pregnant or breastfeeding.

For control group: patients will be excluded if they:(i) have an uncontrolled medical condition (other than cancer); (ii) if they were undertaking 300 min or more of exercise per week (iv) cannot read or understand English; and (iii) are pregnant or breastfeeding: (vi) if they were undertaking 300 min or more of exercise per week

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Participants will be ask to choose between the 3 arms.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Given that this will be a pilot preliminary efficacy trial, no formal sample size calculation was made. However, over a recruitment period of 12 months, the number of patients that is viable is 39 (13 patients in each arm), according to the project clinician.

A Chi-square test will be used to examine the difference of pCR and residual cancer burden between Arm 1 (FMD group) and Arm 3 (control group) and between Arm 2 (exercise program group) and Arm 3 (control group). In addition, logistic regression will be used to analyse the effects of the intervention on the rate of pCR adjusting for tumour subtype. To compare changes from baseline to end of the interventions in biomarkers, anthropometric and body composition measures, and patient-reported outcomes between Arm 1 and Arm 3 and between Arm 2 and Arm 3, an analysis of covariance will be used adjusting for the baseline value. If the data are not normally distributed, data will be log transformed. Pearson correlation, or Spearman correlation coefficient for non-parametric data, will be calculated to quantify the relationship between pCR and biomarkers. Tests will be two-tailed and an alpha level of p=0.05 will be required for statistical significance.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
18/09/2023
Actual
Date of last participant enrolment
Anticipated
20/09/2024
Actual
Date of last data collection
Anticipated
12/05/2025
Actual
Sample size
Target
39
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 24718 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 40337 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 313835 0
University
Name [1] 313835 0
Exercise Medicine Research Institute. Edith Cowan University
Country [1] 313835 0
Australia
Primary sponsor type
University
Name
Exercise Medicine Research Institute. Edith Cowan University
Address
270 Joondalup Dr, Joondalup WA 6027
Country
Australia
Secondary sponsor category [1] 315671 0
None
Name [1] 315671 0
Address [1] 315671 0
Country [1] 315671 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312991 0
South Metropolitan Health Service Human Research Ethics Committee
Ethics committee address [1] 312991 0
South Metropolitan Health Service Executive
Level 2, Education Building, Fiona Stanley Hospital
14 Barry Marshall Parade
MURDOCH Western Australia 6150
Ethics committee country [1] 312991 0
Australia
Date submitted for ethics approval [1] 312991 0
25/07/2023
Approval date [1] 312991 0
29/08/2023
Ethics approval number [1] 312991 0

Summary
Brief summary
This study will evaluate the effects of a fasting mimicking diet or an exercise program on tumour response to neoadjuvant chemotherapy (chemotherapy prior to surgery) in breast cancer patients compared to a group of patients undergoing neoadjuvant chemotherapy without following a diet or exercise program.

Who is it for?
You may be eligible for this study if you are an adult woman aged 18 years or older, you have been diagnosed with breast cancer and you are scheduled to undergo chemotherapy prior to surgery to remove cancerous tissue.

Study details
Participants who choose to enrol in this study will be offered to join one of three groups.
Participants who choose to join the first group will be given a prescribed diet that is designed to mimic a fasting diet. The diet will be low calorie and low protein, participants will be asked to follow the diet 2 days before their chemotherapy infusion and continue it for 2 days after their infusion. Participants will then return to their usual diet until 2 days prior to their next infusion.
Participants who choose to join the second group will be asked to attend a gym 2 or 3 days per week to complete supervised exercise routines. During weeks where participants are undergoing chemotherapy they will attend 2 sessions/week for 50-60 min per session. During the weeks without chemotherapy treatment, patients will attend 3 sessions/week for 50-60 min per session.
Participants who do not wish to participate in either the diet or exercise groups may also enrol in this study and complete blood tests and questionnaires prior to and after completing their chemotherapy. These participants will act as the comparator group to determine if either the diet or exercise program has any effect on the cancer cells compared to chemotherapy alone.

It is hoped this research will provide preliminary evidence as to whether following a fasting mimicking diet or an exercise program while undergoing chemotherapy for breast cancer is able to slow the spread of cancer cells compared to chemotherapy alone. If either the diet or exercise program is shown to have a beneficial effect on breast cancer patients, a larger randomised clinical trial of one or both of these treatments may be undertaken
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 126606 0
Dr Andrew Redfern
Address 126606 0
The University of Western Australia (M582), 35 Stirling Highway, Perth WA 6009Australia
Country 126606 0
Australia
Phone 126606 0
+61 0861511141
Fax 126606 0
Email 126606 0
andrew.redfern@health.wa.gov.au
Contact person for public queries
Name 126607 0
Ms Cristina Crespo Garcia
Address 126607 0
Exercise Medicine Research Institute. Edith Cowan University,Building 21/Off Prilep Dr, Joondalup WA 6027
Country 126607 0
Australia
Phone 126607 0
+61 0431837516
Fax 126607 0
Email 126607 0
c.crespogarcia@ecu.edu.au
Contact person for scientific queries
Name 126608 0
Ms Cristina Crespo Garcia
Address 126608 0
Exercise Medicine Research Institute. Edith Cowan University,Building 21/Off Prilep Dr, Joondalup WA 6027
Country 126608 0
Australia
Phone 126608 0
+61 0431837516
Fax 126608 0
Email 126608 0
c.crespogarcia@ecu.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual participant data will not be available for data dictionaries or other formats. The de-identified data will be stores within the Exercise Medicine Research Institute, in accordance with the National Statement, and earlier approval provided by the Human Research Ethics Committee of Edith Cowan University.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
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