DIetary REstriction as an Adjunct to Neoadjuvant ChemoTherapy for HER2 Negative Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 131
- 试验地点
- 16
- 主要终点
- 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.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Fasting mimicking diet
Short term fasting using Fasting mimicking diet around neoadjuvant chemotherapy (AC>T)
干预措施: Fasting mimicking diet (Other)
regular diet
Standard neoadjuvant chemotherapy (AC>T)
结局指标
主要结局
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.
时间窗: 2 years
Phase II
The percentage of pCR.
时间窗: 4 years
Phase III
次要结局
- 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)
研究者
J.R. Kroep
MD, PhD
Leiden University Medical Center