DIetary REstriction as an Adjunct to Neoadjuvant ChemoTherapy for HER2 Negative Breast Cancer

Phase 2

Completed

• Conditions: Fasting Mimicking Diet; Neoadjuvant Chemotherapy; Breast Cancer; Pathological Complete Response
• Interventions: Other: Fasting mimicking diet

• Registration Number: NCT02126449
• Lead Sponsor: Leiden University Medical Center

Brief Summary

Preclinical studies provide strong support for the concept that fasting evokes resistance to multiple forms of stress. Fasting reduces plasma levels of growth factors and modulates intracellular nutrient sensing systems, thereby diverting energy from growth to maintenance. Accordingly, the currently available preclinical evidence suggests that short-term fasting protects normal cells against the perils of chemotherapy. In contrast, cancer cells are not protected, as a result of their self-sufficiency in growth signals. This phenomenon is termed Differential Stress Resistance (DSR). DSR reduces the severity of toxic side-effects of chemotherapy and interestingly, it simultaneously renders cancer cells more vulnerable to chemotherapeutics. Importantly, extensive preclinical evidence and preliminary clinical data indicate that a specifically designed very low calorie, low amino acid substitution diet ("Fasting Mimicking Diet, FMD") has effects on cancer therapy that are very similar to those of fasting. This study aims to evaluate the impact of the FMD on tolerance to and efficacy of neoadjuvant chemotherapy in women with stage II or III breast cancer.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-02
• Study First Submitted: 2014-02-14
• Study First Submitted QC: 2014-04-28
• Study First Posted: 2014-04-30
• Primary Completion: 2018-11
• Study Completion: 2018-11
• Status Verified: 2019-10
• Last Update Submitted: 2019-10-22
• Last Update Posted: 2019-10-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 131

Inclusion Criteria

• Female patients with stage II or III (cT1cN+ or ≥T2 any cN, cM0) breast cancer receiving neoadjuvant AC-T
• Measurable disease (breast and/or lymph nodes)
• HER2 negative core biopsy Age ≥18 years
• WHO performance status 0-2
• 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
• Patients must be accessible for treatment and follow-up
• Written informed consent according to the local Ethics Committee requirements
• Willing to fill in quality of life questionnaires
• Able to read and write in Dutch

Exclusion Criteria

• History of breast cancer (invasive or non-invasive)
• Previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix.
• Serious other diseases such as recent myocardial infarction, clinical signs of cardiac failure or clinically significant arrhythmias
• Diabetes Mellitus
• Body mass index (BMI) < 19 kg/m2
• Pregnancy or lactating
• Significant food allergies which would make the subject unable to consume the food provided (ex: nuts or soy)
• Any metabolic disorders that may affect gluconeogenesis or adaptation to short fasting periods.
• Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fasting mimicking diet	Fasting mimicking diet	Short term fasting using Fasting mimicking diet around neoadjuvant chemotherapy (AC\>T)

Primary Outcome Measures

Name	Time	Method
The percentage of patients with grade III/IV toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events version (NCI CTCAE) v4.03.	2 years	Phase II
The percentage of pCR.	4 years	Phase III

Secondary Outcome Measures

Name	Time	Method
SNPs used as biomarker to predict treatment outcome.	5 years
Clinical response measured by MRI (RECIST1.1) after 4 cycles chemotherapy.	4 years
Grade I/II side effects of chemotherapy according to NCI CTCAE v4.03.	4 years
DNA damage, apoptosis, immunology and nutrient sensing system activity in the tumor.	5 years
Patient's quality of life (using EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires), burden of therapy noted by a visual analogue scale (VAS) (Distress Thermometer) and differences of Illness Perceptions (B-IPQ).	4 years
Hormone receptor percentage, Ki67 and immunologic tumor profile and tumor/stroma ratio as predictive biomarker	4 years
Metabolic (Glucose, insulin, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein 3 (IGF-BP3), free thyroxin (FT4), triiodothyronine (T3) and thyroid-stimulating hormone (TSH)) and inflammatory response (CRP) to chemotherapy.	4 years
Long term efficacy of treatment (DFS, OS).	4years

Trial Locations

Locations (15)

Kennemer gasthuis; 🇳🇱 Haarlem, Netherlands

Isala; 🇳🇱 Zwolle, Netherlands

OLVG; 🇳🇱 Amsterdam, Netherlands

Amphia Hospital; 🇳🇱 Breda, Netherlands

, Catharina ziekenhuis Hospital; 🇳🇱 Eindhoven, Netherlands

VieCurie Hospital; 🇳🇱 Venlo, Netherlands

Deventer Hospital; 🇳🇱 Deventer, Netherlands

Ziekenhuis Gelderse Valei; 🇳🇱 Ede, Netherlands

Medisch Centrum Leeuwarden; 🇳🇱 Leeuwarden, Netherlands

Haga Hospital; 🇳🇱 The Hague, Netherlands

Lange Land Hospital; 🇳🇱 Zoetermeer, Netherlands

Medisch Centrum Alkmaar; 🇳🇱 Alkmaar, Netherlands

Leids Universitair Medisch Centrum; 🇳🇱 Leiden, Zuid-holland, Netherlands

Alexander Monro hospital; 🇳🇱 Bilthoven, Netherlands

Bronovo Hospital; 🇳🇱 The Hague, Netherlands