Fasting Mimicking Diet, HER2-negative Breast Cancer, Hormone Receptor-positive Breast Cancer, Neoadjuvant Chemotherapy, Objective Response Rate, Pathological Complete Response
Conditions
Brief summary
In preclinical research, short-term fasting (STF) protects tumor-bearing mice against the toxic effects of chemotherapy, improves the CD8+ effector T-cell intratumor infiltration, while enhancing the chemotherapy efficacy. Short-term use of a fasting-mimicking diet (FMD) caused a major increase in the efficacy of cancer treatment in mice comparable to STF. In humans, the investigators recently performed a multicenter randomized phase II trial showing that patients with Human Epidermal growth factor Receptor 2 (HER2) negative breast cancer treated with neoadjuvant chemotherapy and FMD displayed a better radiological response and a better pathological response (90-100% vs \<90% tumor cell reduction) than patients treated with chemotherapy without FMD (de Groot, Nat Commun 2020; NCT02126449). Therefore these findings will be validated in a phase 3 trial with the underlying hypothesis that FMD during neoadjuvant chemotherapy for breast cancer improves clinical outcomes, potentially due to improved local immunity.
Detailed description
STF during neadjuvant chemotherapy aiming to improve the chemotherapy efficacy and decline the side effects in patients with stage II-III HR+, HER2- breast cancer
Interventions
OTHERFasting Mimicking diet program
Fasting mimicking diet by L-Nutra, a 4-day low caloric, low protein, vegetarian diet 3 days prior to and the day of neoadjuvant chemotherapy administration. The FMD will take place every 4 weeks, thus in total 5 times (2x during ddAC, 3x during Paclitaxel) during the neoadjuvant chemotherapy.
Sponsors
The Netherlands Cancer Institute
Borstkanker Onderzoek Groep
Comprehensive Cancer Centre The Netherlands
Koningin Wilhelmina Fonds
World Cancer Research Fund International
L-Nutra Inc
Leiden University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical stage II-III (cT1cN+ or ≥T2 any cN, cM0), HR+, HER2- breast cancer * Detectable and measurable disease (breast and/or lymph nodes) * World Health Organization (WHO) performance status 0-2 * Adequate organ function assessed by standard pre-treatment assessment: * Adequate bone marrow function: white blood cells (WBCs) ≥3.0 x 109/l, neutrophils ≥1.5 x 109/l, platelets ≥100 x 109/l * Adequate liver function: bilirubin ≤1.5 x upper limit of normal (UNL) range, ALAT and/or ASAT ≤2.5 x UNL, Alkaline Phosphatase ≤5 x UNL * Adequate renal function: the calculated creatinine clearance should be ≥50 mL/min * Available for treatment and follow-up * Written informed-consent * Willing to fill in Quality Of Life and Cognition questionnaires * Ability to read and understand Dutch language, accessibility to a computer with internet connection and independent use of computer
Exclusion criteria
* Patient history of invasive or ipsilateral non-invasive breast cancer * Active malignancy in the last 5 years, with the exclusion of basal cell carcinoma or pre-invasive cervical neoplasia/dysplasia. * Body mass index (BMI) \< 18.5 kg/m2 * Pregnancy or lactating * Food allergy for ingredients of FMD (nuts, soy, honey) * A metabolic condition affecting gluconeogenesis or adaptation to periodic fasting. (Diabetes Mellitus for example)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate assessed by MRI (RECIST1.1) after 4 ddAC cycles and at the end of chemotherapy | 4.5 years |
| Pathological response rate (pCR). Both percentage of pCR and 90-100% tumor loss according to Miller & Payne | 4.5 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events ≥grade 3 (maximum of total) difference between treatment arms during neoadjuvant chemotherapy (ddAC, paclitaxel and total). | 4.5 years | — |
| Cognition assessed by Amsterdam Cognition Scan (ACS) online battery consisting of 7 online neuropsychological tests | 5 years | online questionnaires take place at baseline, before surgery and 6 months after surgery. |
| Determine the effect of FMD on local immunomodulation and tumor immunity | 6 years | By analyzing the immune-composition and gene-expression profile using multispectral Vectra imaging and Nanostring analyses respectively, in tumor samples taken at baseline (diagnostic), after 4 cycles and resection specimen |
| Quality of Life assessed by online questionnaires (EORTC QLQ-C30, EORTC QLQ-BR23), burden of therapy (Distress Thermometer) and Illness Perceptions (B-IPQ) | 5 years | Validated online questionnaires take place at baseline, after 4 ddAC cycles, before surgery and 6 months after surgery. |
| Determine the effect of treatment on the 3 and 5 year Event-free survival (EFS) and Overall survival (OS) | 7.5 and 9.5 years | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Biomarker analysis to predict treatment outcome | 6 years | Genetic and/or epigenetic analysis will be performed on blood samples by for example PCR and/or GWAS technique. |
| Optional Bioelectrical Impedance Analysis (BIA) for participants at the Leiden University Medical Center (LUMC) to investigate the change in body composition in both treatment arms. | 4.5 years | — |
Countries
Netherlands
Outcome results
None listed