FMD and Neoadjuvant Chemo-immunotherapy in TNBC

Official title

FAsting-mimicking Diet in Combination With Neoadjuvant Chemo-immunoTherapy for Early or Locally Advanced Triple-Negative Breast Cancer: the Prospective, Single-arm, Open-lable, Phase 2 FACT-TN Trial

Overview

The primary objective of this study is to investigate the efficacy and safety of a fasting-mimicking diet (FMD) intervention combined with standard neoadjuvant chemoimmunotherapy in early-stage or locally advanced triple-negative breast cancer (TNBC).

Detailed description

Despite the significantly superior efficacy of neoadjuvant chemoimmunotherapy, a considerable proportion of early-stage treated triple-negative breast cancer (TNBC) patients ultimately experience recurrence, particularly those who do not achieve pathological complete response (pCR) after surgery. Therefore, there is an urgent need to develop new and effective treatment strategies to improve outcomes for TNBC patients. Additionally, selecting patients who are more likely to benefit from neoadjuvant chemotherapy combined with immunotherapy remains a clinical challenge. The fasting-mimicking diet (FMD) is a strictly calorie-restricted, low-sugar, low-protein, and high-fat dietary regimen that shares metabolic and anti-tumor effects with water-only fasting while reducing the risk of severe adverse reactions, leading to extensive exploration in both preclinical and clinical settings. Numerous clinical trials in breast cancer and various other cancers have investigated FMD, consistently demonstrating that FMD enhances the efficacy of standard anti-tumor therapies with a favorable safety profile. Furthermore, FMD has shown potent immunomodulatory effects in both in vivo studies and cancer patients, with the activation of anti-tumor immunity being a key mechanism underlying the anti-cancer effects of FMD alone or in combination with chemotherapy. Based on the above research background, this study focuses on operable early-stage or locally advanced triple-negative or near-triple-negative breast cancer. Patients will receive neoadjuvant standard chemotherapy combined with immunotherapy alongside FMD dietary intervention, aiming to explore the efficacy and safety of FMD dietary intervention in combination with standard neoadjuvant therapy for breast cancer patients.

Interventions

• Other Fasting-mimicking diet
  The Fasting-Mimicking Diet (FMD) will be administered every three weeks for a maximum of 8 consecutive cycles, unless side effects necessitate its temporary or permanent discontinuation. Each FMD cycle will consist of a specific FMD regimen for five consecutive days, repeated every three weeks. The FMD regimen is a plant-based, low-calorie (approximately 738 kcal on Day 1; approximately 536 kcal on Days 2 to 5), low-protein, low-carbohydrate diet. All patients will follow the identical prescrib
• Drug Chemotherapy
  All enrolled patients received standard preoperative chemotherapy combined with anti-PD-1 therapy. The neoadjuvant regimens were guideline-recommended protocols: TP×4-AC×4 combined with PD-1 inhibitor, TP plus PD-1 inhibitor, or PD-1 inhibitor combined with other taxane-based regimens. * T: Taxanes, including docetaxel, nab-paclitaxel, and paclitaxel. * P: Platinum agents. * A: Anthracyclines, including epirubicin, pirarubicin, and doxorubicin. * C: Cyclophosphamide.
• Drug Toripalimab
  In the neoadjuvant phase, toripalimab (anti-PD-1) was dosed intravenously at 240 mg on day 1 of every 21-day cycle.

Primary outcome measures

• Total pathological complete response (pCR) rate [Time frame: One week post-operation for the last enrolled patient]

Secondary outcome measures (6)

• Rate of Residual Cancer Burden (RCB) of 0-1 [Time frame: One week post-operation for the last enrolled patient.]
• Objective Response Rate (ORR) [Time frame: Two weeks after the end of the final cycle (each cycle is 21 days) for the last enrolled patient.]
• Event-Free Survival (EFS) [Time frame: Three years after the last patient is enrolled]
• Adverse events (AEs) [Time frame: One year after the last patient is enrolled]
• Change in Quality of Life (QoL) scores on the EORTC QLQ-C30 questionnaire [Time frame: From baseline to 3 years after surgery]
• Change in Quality of Life (QoL) scores on the EORTC QLQ-BR 23 questionnaire [Time frame: From baseline to 3 years after surgery]

Eligibility criteria

Inclusion criteria

• Written informed consent obtained from the patient or their legal representative.
• Good patient compliance, willing and able to adhere to the prescribed dietary intervention plan, visits, treatment schedule, laboratory tests, and other study procedures.
• Female, aged 18 to 70 years.
• ECOG performance status score of 0 to 1, with an expected survival of >12 weeks.
• Female patients of childbearing potential must agree to use reliable methods of contraception from before trial entry, throughout the study, and for 8 weeks after the completion of the study.
• Patients with pathologically confirmed primary breast cancer, with a primary tumor ≥2 cm and regional lymph node status N0-N3 (AJCC Version 8); patients with positive lymph nodes may have a primary tumor of any size; no distant metastases (M0).
• Triple-negative or near-triple-negative subtype, defined as HR-negative or low expression (ER and/or PR positivity rate 1%-10%) and HER2-negative (IHC 0, 1+, or 2+ with FISH-negative).
• No prior history of any anti-tumor therapy, including chemotherapy, radiotherapy, and biological therapy.
• Hemoglobin ≥90 g/L (can be maintained or exceed this level via transfusion).
• Absolute neutrophil count ≥1.5 × 10E9/L.
• Platelet count ≥100 × 10E9/L.
• Total bilirubin ≤1.5 × upper limit of normal (ULN).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN.
• Creatinine ≤1.5 × ULN.
• Fasting blood glucose <250 mg/dL (13.89 mmol/L).
• Pregnancy must be ruled out for women of childbearing potential (aged 15-49).

Exclusion criteria

• Previous administration of any systemic anti-cancer therapy, including cytotoxic chemotherapy, targeted therapy, immunotherapy, or investigational treatment.
• Prior radiotherapy for breast cancer.
• Documented evidence (pathological or radiological) of distant metastasis prior to treatment initiation.
• History of another malignancy within the five years preceding treatment initiation in this study, except for carcinoma in situ of the cervix, cured basal cell carcinoma, or urothelial tumors of the bladder (including Ta and Tis).
• Known allergy or hypersensitivity to any component of the investigational drugs or products.
• Active autoimmune disease requiring systemic treatment (e.g., systemic lupus erythematosus, psoriasis, etc.).
• Body Mass Index (BMI) < 19 kg/m².
• Unintentional weight loss ≥5% within the past 3 months, unless the patient's BMI >22 kg/m² and weight loss at study entry is <10%; or unintentional weight loss ≥10% within the past 3 months, unless the patient's BMI >25 kg/m² and weight loss at study entry is <15%. In either case, weight must have been stable for at least one month prior to enrollment.
• Eating disorders, including anorexia nervosa, bulimia nervosa, etc.
• Baseline fasting blood glucose ≤60 mg/dL (3.33 mmol/L).
• Severe infection within 4 weeks prior to enrollment, including but not limited to hospitalization for infectious complications, bacteremia, or severe pneumonia.
• Type 1 or Type 2 diabetes mellitus requiring medication (including but not limited to insulin or insulin secretagogues), with the exception of metformin.
• Any unstable systemic disease, including: uncontrolled hypertension, unstable angina, angina pectoris with onset within the last 3 months, congestive heart failure, myocardial infarction (within 6 months prior to enrollment).
• Severe arrhythmia requiring medication, or significant hepatic, renal, or metabolic disease.
• Known infection with Human Immunodeficiency Virus (HIV).
• Active, uncontrolled hepatitis B or hepatitis C.
• Pregnant or lactating women.
• History of diagnosed neurological or psychiatric disorders, including epilepsy or dementia.
• Any other condition deemed by the investigator as unsuitable for participation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sun Yat-sen University Cancer Center — Guangzhou

Identifiers

NCT: NCT07378306 · B2025-861-01 · GASTO-10140

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗