Fasting Mimicking Diet Program to ImpRovE ChemoTherapy in Hormone Receptor Postive (HR+), HER2- Breast Cancer

Phase 3

Suspended

• Conditions: Neoadjuvant Chemotherapy; Fasting Mimicking Diet; Pathological Complete Response; Hormone Receptor-positive Breast Cancer; Objective Response Rate; HER2-negative Breast Cancer
• Interventions: Other: Fasting Mimicking diet program

• Registration Number: NCT05503108
• Lead Sponsor: Leiden University Medical Center

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

Study Timeline

• Study First Submitted: 2022-07-24
• Study First Submitted QC: 2022-08-15
• Study First Posted: 2022-08-16
• Study Start: 2023-03-17
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-20
• Last Update Posted: 2023-11-22
• Primary Completion: 2024-01-01
• Study Completion: 2024-01-01

Recruitment & Eligibility

• Status: SUSPENDED
• Sex: All
• Target Recruitment: 10

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fasting Mimicking Diet group	Fasting Mimicking diet program	Fasting Mimicking Diet 3 days before and the day of neoadjuvant chemotherapy (ddAC, T)

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Adverse events ≥grade 3 (maximum of total) difference between treatment arms during neoadjuvant chemotherapy (ddAC, paclitaxel and total).	4.5 years
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
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.
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.

Trial Locations

Locations (7)

Noordwest Ziekenhuisgroep; 🇳🇱 Alkmaar, Netherlands

Rode Kruis ziekenhuis; 🇳🇱 Beverwijk, Netherlands

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands

Alexander Monro Ziekenhuis; 🇳🇱 Bilthoven, Netherlands

Ziekenhuis Gelderse Vallei; 🇳🇱 Ede, Netherlands

Reinier de Graaf ziekenhuis; 🇳🇱 Delft, Netherlands

Deventer Ziekenhuis; 🇳🇱 Deventer, Netherlands