2023-508920-37-00招募中2 期
Targeting triple negative BREAst cancer metabolism with a combination of chemotherapy and a diet mimicking FASTing plus/minus metformin in the preoperative setting: the BREAKFAST trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Pathologic complete response (pCR), as defined as the absence of residual tumor cells in both breast tissue and axillary lymph nodes.
研究概览
简要总结
To investigate if the experimental treatments, consisting in the combination of triweekly anthracycline-taxane chemotherapy with cyclic FMD, with or without daily metformin, are able to increase the rate of pCR when compared to historical results with standard anthracycline-taxane chemotherapy.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female patients are not of childbearing potential if they meet at least one of the following criteria: a. Have undergone a documented hysterectomy and/or bilateral oophorectomy b. Have medically confirmed ovarian failure c. Achieved post-menopausal status, defined as: ≥ 12 months of non-therapy-induced amenorrhea or surgically sterile (absence of ovaries) and have a serum FSH level within the laboratory’s reference range for postmenopausal females.
- •Age ≥ 18 and ≤ 75 years.
- •Evidence of a personally signed and dated informed consent document (ICD) indicating that the patient has been informed of all pertinent aspects of the study before enrollment
- •Willingness and ability to comply with the prescribed FMD regimen, metformin intake, the scheduled visits, treatment plans, laboratory tests and other procedures
- •Histologically confirmed diagnosis of invasive TNBC candidate to neoadjuvant chemotherapy and subsequent curative surgery. On the basis of International Guidelines, TNBC is defined by absent or minimal (<1%) expression of oestrogen and progesterone receptors at IHC, and absence of HER2 over-expression or amplification, as defined as an IHC score of 0, 1+, or an IHC score of 2+ with in situ hybridization (ISH) analysis excluding HER2 gene amplification
- •Patients with localized disease (clinical stage I-III according to TNM). Patients with Stage I TNBC will be included only if the primary tumor is at least 10 mm in greatest dimension (clinical T1c as determined through baseline CESM and CE-MRI assessment).
- •Presence of an Eastern Cooperative Oncology Group (ECOG) performance status 0 or
- •Presence of adequate bone marrow and organ function as defined by the following laboratory values: a. ANC ≥ 1.5 x 10^3/lb. platelets ≥ 100 x 10^3/l c. hemoglobin ≥ 9.0 g/dl d. calcium (corrected for serum albumin) within normal limits or ≤ grade 1 according to NCI-CTCAE version 5.0 if not clinically significant e. potassium within the normal limits, or corrected with supplements f. creatinine < 1.5 ULN g. blood uric acid < 10 mg/dl h. ALT and AST ≤ 2 x ULN i. total bilirubin < 1.5 ULN except for patients with Gilbert syndrome who may only be included if the total bilirubin is < 3.0 x ULN or direct bilirubin < 1.5 x ULN j. Fasting glucose ≤ 250 mg/dl.
- •Female patients of childbearing potential must agree to sexual abstinence or to use two highly effective methods of contraception throughout the study and for at least six months after the end of the FMD. Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the patient. Examples of contraceptive methods with a failure rate of < 1% per year include tubal ligation, male sterilization, hormonal implants, established, proper use of combined oral or injected hormonal contraceptives, and certain intrauterine devices. Alternatively, two methods (e.g., two barrier methods such as a condom and a cervical cap) may be combined to achieve a failure rate of < 1% per year. Barrier methods must always be supplemented with the use of a spermicide. A patient is of childbearing potential if, in the opinion of the Investigator, she is biologically capable of having children and is sexually active.
排除标准
- •Prior systemic treatment for breast cancer or other malignancies within 5 years of treatment enrollment.
- •Active autoimmune diseases requiring systemic treatments (e.g. systemic steroids or immune suppressants).
- •Active chronic therapy with systemic steroids at a dose ≥ 10 mg per day of prednisone or equivalent at study enrollment
- •Known recent diagnosis of hypothyroidism requiring systemic replacement hormonal therapy and without stabilization of hormonal profile (fT3, fT4 and TSH within the normal range).
- •Diagnosis of type 1 or 2 diabetes mellitus requiring pharmacologic therapy (including, but not limited to, insulin, secretagogues and metformin). A diagnosis of type 2 diabetes mellitus not requiring pharmacological treatments based on the judgment of a diabetologist, is compatible with patient enrollment in the trial.
- •Active gastric or intestinal ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small intestine resection.
- •Anamnesis of clinically significant heart disease including: a. angina pectoris, coronary bypass, symptomatic pericarditis, myocardial infarction in the previous 12 months from the beginning of experimental therapy; b. congestive heart failure (NYHA III-IV).
- •Anamnesis of clinically meaningful cardiac arrhythmias, such as ventricular tachycardia, chronic atrial fibrillation, complete bundle branch block, high grade atrio-ventricular block like bi-fascicular block, type II Mobitz and third grade atrio-ventricular block, nodal arrhythmias, supra-ventricular arrhythmia.
- •Left ventricular ejection fraction lower than 50% at the cardiac scan with radionuclides or at echocardiography.
- •Previous episodes of symptomatic hypotension leading to loss of consciousness.
- •Baseline plasma fasting glucose ≤ 60 mg/dL.
- •Prior treatment with anthracyclines
- •Medical or psychiatric comorbidities rendering the patient not candidate to the clinical trial, according to the investigator’s judgement.
- •Other cardiac, liver, lung or renal comorbidities, not specified in the previous inclusion or exclusion criteria, but potentially exposing the patient to a high risk of lactic acidosis.
- •Diagnosis of other malignancies in advanced stages (unresectable, locally advanced or metastatic), or that required systemic (neo)adjuvant chemotherapy in the previous 5 years. Other malignancies diagnosed more than 5 years before the diagnosis of breast cancer must have been radically treated without evidence of relapse at the moment of patient enrollment in the trial
- •Body mass index (BMI) < 20 kg/m^
- •History of alcohol abuse.
- •Non-intentional weight loss ≥ 5% in the previous 3 months, unless the patient has a BMI > 22 kg/m^2 and weight loss has been lower than 10% at the time of enrollment in the study; or non-intentional weight loss of ≥ 10% in the previous 3 months, unless the patients has a BMI > 25 kg/m^2 and weight loss has been lower than 15% at the time of the enrollment in the study. In both cases, weight must have been stable for at least one month before study enrollment
- •Active pregnancy or breast feeding.
- •Known active B or C hepatitis or human immunodeficiency virus (HIV) infection, or occasional finding of active hepatitis B/C infection during screening tests before chemotherapy initiation, as defined as positive polymerase chain reaction (PCR) testing for HBV-DNA and HCV-RNA and qualitative PCR for HIV-RNA, or requiring active treatment at study enrollment.
- •Serious infections in the previous 4 weeks before the FMD initiation, including, but not limited to, potential hospitalizations for complications of infections, bacteriemia or serious pneumonitis.
结局指标
主要结局
Pathologic complete response (pCR), as defined as the absence of residual tumor cells in both breast tissue and axillary lymph nodes.
Pathologic complete response (pCR), as defined as the absence of residual tumor cells in both breast tissue and axillary lymph nodes.
次要结局
- Relapse free survival (RFS), as defined as the time from surgery to tumor recurrence, either local or distant
- Distant metastasis free survival (DMFS), as defined as the time from surgery to the occurrence of distant metastases
- Overall Survival (OS), as defined as the time from randomization to the date of death. Patients alive at time of data cut-off and analysis will be censored at their last contact date
- Metabolic biomarkers (e.g. plasma glucose, insulin, insulin-like growth factor 1 (IGF-1) levels and whole blood and plasma lipid profile, fecal microbiota) assessed at baseline and at each chemotherapy cycle
- Role of DNA repair, mTORC 1, PP2A, autophagy and Beclin 1 pathways in the efficacy of the experimental treatments, defined as the rate of pCRs
- Dose-intensity, that is the dose of effective drug administrated per unit of time (e.g. mg/m2/week)
- Percentage of patients with drug dose and/or time modifications
- Percentage of patients with experimental dietary regimen modifications
- Percentage of premature withdrawals
- Incidence, nature, severity and seriousness of AEs, according of NCI-CTCAE, version 5.0
- Maximum toxicity grade experienced by each patient for each specific toxicity
- Percentage of patients experiencing grade 3-4 toxicity for each specific toxicity
- Patients with at least a SAE
研究者
Clinical Trials Center
Scientific
Fondazione IRCCS Istituto Nazionale Dei Tumori
研究点 (1)
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