DIRECT-2: Fasting Mimicking Diet Program to ImpRovE ChemoTherapy in HR+, HER2- Breast Cancer
试验速览
- 阶段
- 3 期
- 状态
- 暂停
- 发起方
- 入组人数
- 10
- 试验地点
- 8
- 主要终点
- Objective response rate assessed by MRI (RECIST1.1) after 4 ddAC cycles and at the end of chemotherapy
研究概览
简要总结
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.
详细描述
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
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
结局指标
主要结局
Objective response rate assessed by MRI (RECIST1.1) after 4 ddAC cycles and at the end of chemotherapy
时间窗: 4.5 years
Pathological response rate (pCR). Both percentage of pCR and 90-100% tumor loss according to Miller & Payne
时间窗: 4.5 years
次要结局
- Adverse events ≥grade 3 (maximum of total) difference between treatment arms during neoadjuvant chemotherapy (ddAC, paclitaxel and total).(4.5 years)
- Determine the effect of treatment on the 3 and 5 year Event-free survival (EFS) and Overall survival (OS)(7.5 and 9.5 years)
- Determine the effect of FMD on local immunomodulation and tumor immunity(6 years)
- Quality of Life assessed by online questionnaires (EORTC QLQ-C30, EORTC QLQ-BR23), burden of therapy (Distress Thermometer) and Illness Perceptions (B-IPQ)(5 years)
- Cognition assessed by Amsterdam Cognition Scan (ACS) online battery consisting of 7 online neuropsychological tests(5 years)
研究者
J.R. Kroep
Drs J.R. Kroep
Leiden University Medical Center