Time restricted Eating And Metformin (TEAM) in invasive breast cancer (IBC) or ductal carcinoma in situ (DCIS). A randomized, phase IIb, window of opportunity presurgical trial.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 90
- 试验地点
- 2
- 主要终点
- Frequency of occurrence of dose limiting toxicity in the first 14 patients in the experimental arm (interim endpoint); change in pre-post treatment immunohistochemical Ki67 LI in IBC or DCIS (in the absence of IBC) (primary) and difference in post-treatment adjacent DCIS (in the presence of IBC), if present, or IEN (defined as ADH/ALH/LCIS) Ki67 (co-primary) between arms.
研究概览
简要总结
Primary interim objective: assess the safety of the experimental intervention based on the frequency of occurrence of a Dose Limiting Toxicity (DLT) in the first 14 participants assigned to the experimental treatment arm. A DLT is defined as a hypoglycemic event requiring permanent discontinuation of study treatment or any grade 3 or greater adverse event (AE) possibly, probably, or definitely related to the study drug. Primary objective: assess the effect of the combination of prolonged nightly fasting (>=16 hours) and Metformin on the change of Ki67 labeling index (LI) in cancer tissue (IBC or DCIS, if IBC is absent) between pre-treatment biopsy and post treatment surgical specimen. Co-primary objective: evaluate the difference in post-treatment Ki67 LI in cancer adjacent DCIS (in the presence of IBC) or IEN, defined as atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia (ALH) or lobular carcinoma in situ (LCIS), between the active treatment and the control group.
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
- •Women with histologically confirmed ER+ve and/or PgR+ve ≥1% operable IBC (cT1-2, cN0-1, Mx) candidate to elective surgery and not to neo-adjuvant treatment. Women with larger tumors who refuse neo-adjuvant chemotherapy before surgery can also be eligible. ER+ve and/or PgR+ve ≥1% , HER2+ve (cT1, cN0) IBC and DCIS are also eligible.
- •Age ≥ 18 years
- •ECOG performance status ≤1 (Karnofsky ≥70%)
- •Participants must have normal organ and marrow function as defined below: Leukocytes ≥3,000/microliter Absolute neutrophil count ≥1,500/microliter Platelets ≥100,000/microliter AST (SGOT)/ALT (SGPT) ≤1.5 × institutional upper limit of normal Creatinine clearance estimated > 45 mL/min with Cockcroft-Gault formula
- •Female participants of child-bearing potential must agree to use contraception such as barrier method of birth control or abstinence, prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she has to inform her study physician immediately. The effects of Metformin Hydrochloride Extended Release on the developing human fetus at the recommended therapeutic dose are unknown.
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •BMI < 18.5 Kg/m
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •History of lactic acidosis.
- •Liver dysfunction including chronic active hepatitis and cirrhosis not compensated.
- •History of vitamin B12 deficiency or megaloblastic anemia.
- •Chronic use of large doses of diuretics (e.g., >80 mg furosemide)
- •Current use of oral hormonal contraceptives or female hormones in the last four weeks or 5 half-lives, excluding vaginal creams and IUDs.
- •Concomitant use of Topiramate or other carbonic anhydrase inhibitors (e.g., Zonisamide, Acetazolamide or Dichlorphenamide)
- •Concomitant use of GLP-1 medications (e.g. liraglutide, semaglutide, etc.).
- •Pregnant or lactating women. Pregnant women are excluded from this study because even though published data from post-marketing studies have not reported a clear association between Metformin Hydrochloride Extended Release and major birth defects, miscarriage, or adverse maternal or fetal outcomes when Metformin Hydrochloride Extended Release was used during pregnancy, these studies cannot definitely establish the absence of any Metformin Hydrochloride Extended Release associated risk because of methodological limitations, including small sample size and inconsistent comparator groups. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with Metformin Hydrochloride Extended Release, breastfeeding should be discontinued if the mother is treated with Metformin Hydrochloride Extended Release. Moreover, prolonged fasting is not recommended in pregnant woman.
- •Women who practice any type of intermittent fasting program.
- •Previous treatment for breast cancer including chemotherapy and endocrine therapy within the last 12 months.
- •Women who will not have anyone available to assist them in case of need.
- •Women who are planned to receive neoadjuvant therapy
- •Triple negative BC.
- •Patients with history of cancer within the last year. NOTE: Non melanoma skin cancer is allowed.
- •Documented history of symptomatic hypoglycemia.
- •Diabetic patients or participants with fasting glucose level ≥ 126 mg/dL.
- •Known hypersensitivity or intolerance to Metformin Hydrochloride Extended Release.
- •Participants should not be receiving any other investigational agents.
结局指标
主要结局
Frequency of occurrence of dose limiting toxicity in the first 14 patients in the experimental arm (interim endpoint); change in pre-post treatment immunohistochemical Ki67 LI in IBC or DCIS (in the absence of IBC) (primary) and difference in post-treatment adjacent DCIS (in the presence of IBC), if present, or IEN (defined as ADH/ALH/LCIS) Ki67 (co-primary) between arms.
Frequency of occurrence of dose limiting toxicity in the first 14 patients in the experimental arm (interim endpoint); change in pre-post treatment immunohistochemical Ki67 LI in IBC or DCIS (in the absence of IBC) (primary) and difference in post-treatment adjacent DCIS (in the presence of IBC), if present, or IEN (defined as ADH/ALH/LCIS) Ki67 (co-primary) between arms.
次要结局
未报告次要终点
研究者
Andrea De Censi
Scientific
Ente Ospedaliero Ospedali Galliera Di Genova