Fasting-mimicking diet plus chemo‑immunotherapy for early or locally advanced triple‑negative breast cancer

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

We will try adding a fasting-mimicking diet to standard pre-surgery chemotherapy and immunotherapy (toripalimab) in women with early-stage or locally advanced triple-negative breast cancer to see if it improves tumor response and is safe.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years to 70 Years
• Sex: Female
• Sponsor: Sun Yat-sen University (other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT07378306 on ClinicalTrials.gov

What this trial studies

In this phase 2 study, women with operable early-stage or locally advanced triple-negative breast cancer will follow a prescribed fasting-mimicking diet around cycles of standard neoadjuvant chemotherapy combined with the PD-1 antibody toripalimab. The fasting-mimicking diet is a short, calorie-restricted, low-protein, low-sugar, high-fat regimen designed to reproduce metabolic effects of fasting while reducing severe side effects. Key outcomes include pathological complete response at surgery, safety and tolerability, and changes in immune and metabolic biomarkers measured during treatment. Participants will be monitored with clinical visits, imaging, laboratory tests, and surgical pathology to determine treatment effects.

Who should consider this trial

Good fit: Women aged 18–70 with pathologically confirmed triple-negative or near–triple-negative breast cancer who have operable early-stage or locally advanced disease (primary tumor ≥2 cm or any size if nodes are positive), ECOG 0–1, and willingness to follow the fasting-mimicking diet and visit schedule.

Not a fit: Patients with distant metastatic disease, HER2-positive tumors, major uncontrolled comorbidities, inability or unwillingness to follow a calorie-restricted diet, or contraindications to chemotherapy or immunotherapy are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, the combination could increase the chance of complete tumor disappearance before surgery and reduce the risk of recurrence.

How similar studies have performed: Multiple preclinical and clinical studies in breast and other cancers have shown that fasting-mimicking diets can enhance chemotherapy effects and modulate anti-tumor immunity, though combining FMD specifically with chemo‑immunotherapy in TNBC remains under active study.

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.

Where this trial is running

Guangzhou, Guangdong

• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Principal investigator: Jun Tang, MD — Sun Yat-Sen University Cancer Center
• Study coordinator: Jun Tang, MD

Conditions: Breast Cancer, triple-negative breast cancer, fasting-mimicking diet, neoadjuvant, chemo-immunotherapy