Fasting Mimicking Diet Program to ImpRovE ChemoTherapy in Hormone Receptor Postive (HR+), HER2- Breast Cancer (DIRECT-2)

Leiden University Medical Center (LUMC)

Status and phase: Suspended; Phase 3

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

Treatments: Other: Fasting Mimicking diet program

Study type: Interventional

Funder types: Other; NETWORK; Industry

Identifiers

NCT05503108

BOOG 2022-01 (Other Identifier)

P22.028 (Other Identifier)

NL80749.058.22 DIRECT 2

Details and patient eligibility

About

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.

Full 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

Enrollment: 10 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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10 participants in 2 patient groups

Fasting Mimicking Diet group

Experimental group

Description:

Fasting Mimicking Diet 3 days before and the day of neoadjuvant chemotherapy (ddAC, T)

Treatment:

Other: Fasting Mimicking diet program

Normal Diet group

No Intervention group

Description:

Standard neoadjuvant chemotherapy (ddAC, T)