Multicenter, First-line Metastatic Open-label Prospective Phase II Trial Evaluating the Combination of Palbociclib (CDK 4/6 Inhibitor) and Hormone Therapy (Letrozole or Anastrozole) in Women With Luminal, HER2 Negative Advanced Breast Cancer: Evaluation of the Prediction of Individual Treatment Efficacy Using Infrared Laser Spectroscopy Analysis on Liquid Biopsies (Quantum Optics).
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 80
- 试验地点
- 7
- 主要终点
- Rate of Objective Clinical Response
研究概览
简要总结
This study is a multicenter, international, open-label phase II study. Based on inclusion/exclusion criteria, eligible pre and postmenopausal patients with newly diagnosed metastatic luminal hormone receptor-positive and HER2 negative breast cancer, will be prospectively treated with a standard combination of hormone therapy (Letrozole or Anastrozole) and Palbociclib. This combination will continue until progression. Treatment response will be evaluated every three months using clinical and radiological assessments (Revised RECIST guidelines).
Patients will undergo serial liquid biopsies (blood tests) for plasma molecular fingerprinting by the Quantum Optics technology. This study will be the first program exploring the adjunction of the Quantum Optics technology on liquid biopsies to define individual 'molecular fingerprinting profiles' to predict the individual therapeutic effects of Palbociclib combined with Aromatase Inhibitors (AI) (plus ovarian function suppression (OFS) for pre/peri-menopausal patients) in luminal hormone receptor-positive and HER2 negative advanced breast cancer. Batteries of algorithmic tests will integrate the variables obtained by Quantum Optics (to evaluate the efficacy or not of the combination of Palbociclib + Aromatase Inhibitors (AI) ). This approach introduces the concept of singularity to break from the classic idea of "one size fits all".
详细描述
Background:
The standard therapy of first-line metastatic luminal hormone receptor positive, HER2 negative breast cancer, is based upon the combination of hormone therapy (HT): an aromatase inhibitor (AI) (e.g. Anastrozole or Letrozole) and a CDK 4/6 inhibitor (e.g. Palbociclib). Around 50% of patients are benefiting from this combination. However, there are no predictive markers to identify upfront the benefiting population, thus imposing to treat the whole population (100%) for the benefit of 50%.
Objectives:
Primary:
- Rate of objective clinical response for the combination of Palbociclib + AI.
- Value of quantum optics (QO) analysis on liquid biopsies to predict the upfront efficacy/resistance of the combination (Palbociclib + AI) on an individual basis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •To be enrolled in the study, patients should meet the following inclusion criteria:
- •Written informed consent before beginning specific protocol procedures including expected cooperation of the patients for the treatment and follow-up must be obtained and documented according to the local regulatory requirements.
- •Postmenopausal women or pre/peri-menopausal women with Surgical oophorectomy (preferred) or Analogs of LHRH.
- •Performance status < 3 (according to WHO criteria).
- •Histologically confirmed breast cancer (Luminal A or B).
- •Estrogen Receptor positive (ER > 1%).
- •HER2 negative (score 0 or 1 by immunochemistry), FISH negative if IHC score
- •Clinical stage IIIb & IV.
- •Women with De novo advanced luminal HER2 negative advanced breast cancer without other prior systemic treatment for advanced disease.
- •Women with luminal HER2 negative advanced breast cancer either with secondary resistance (relapse after 2 years of adjuvant hormone therapy or within 12 months of completion of adjuvant HT) or sensitivity to adjuvant HT (relapse > 12 months after completion of adjuvant HT).
- •Measurable or evaluable disease.
- •Hematology:
- •Neutrophil count ≥ 1.5 G/L,
- •Platelet count ≥ 100 G/L,
- •Leucocyte count > 3.0 G/L,
- •Hb> 9g/dl.
- •Hepatic function:
- •Total bilirubin ≤ 1.5 times the upper normal limit (UNL),
- •ASAT ≤ 2.5xUNL,
- •ALAT ≤ 2.5xUNL,
- •Alkaline phosphatase ≤ 2.5 times the upper normal limit (UNL).
- •Renal function:
- •Serum creatinine ≤1.5xUNL (and if Serum creatinine >1.5xUNL, creatinine clearance ≥40 mL/min),
- •Metabolic function:
- •Serum calcium ≥ lower limit of normal.
- •Negative pregnancy test (urine or serum) within 7 days before registration for all women of childbearing potential. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures during study treatment.
- •Patients with negative Human Immunodeficiency Virus (HIV) and/or Hepatitis B and/or Hepatitis C results.
排除标准
- •To be enrolled in the study, patients should meet the following exclusion criteria:
- •Male patients.
- •HER2 positive tumors or unknown HR/HER2 status.
- •Triple-negative Breast Cancer (ER<1%).
- •Pregnant or breast-feeding women, or those who plan to become pregnant within 6 months post-treatment.
- •No willingness to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months post-treatment.
- •Any form of breast cancer other than those described in the inclusion criteria, particularly inflammatory and/or loco-regional disease (stages I, II & IIIa).
- •Non-evaluable tumor.
- •Bilateral breast cancer.
- •Patients with a history of other cancer, except in situ cervical cancer or baso-cellular skin cancer, considered cured.
- •Patient has another disease, which is deemed incompatible with the inclusion in the protocol.
- •Heart, kidney, medullary, respiratory or liver failure.
- •Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) at baseline.
- •History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease at baseline,
- •Acute urinary infection, ongoing hemorrhagic cystitis at baseline.
- •Uncontrolled diabetes.
- •Symptomatic or progressive disorder of the central nervous system (CNS) at baseline.
- •Patients with positive Human Immunodeficiency Virus (HIV) and/or Hepatitis B and/or Hepatitis C results.
- •Significant psychiatric abnormalities.
- •History of hypersensitivity to studied treatment or excipients.
- •Known previous or ongoing abuse of narcotic drug, other medication or alcohol.
- •Any investigational agent within 30 days before initiation of study treatment.
- •Patient unwilling or unable to comply with study requirements.
研究组 & 干预措施
Palbociclib + Aromatase Inhibitors (AI) (Letrozole or Anatrozole)
The participants will receive a combination of: Palbociclib (125 mg daily per os (3 weeks on-1 week off) with dose adaptation according to safety profile) and non-steroidal aromatase inhibitor (Letrozole (2.5mg ) or Anastrozole (1mg) daily per os). This combination will continue until progression for an average duration of 2 years.
干预措施: Combination of Palbociclib and aromatase inhibitor (Letrozole or Anastrozole) (Drug)
结局指标
主要结局
Rate of Objective Clinical Response
时间窗: From date of first treatment until the date of the first documented progression, assessed up to 2 years.
The objective clinical response will be assessed with Radiological evaluation according to the RECIST revised criteria for the combination of Palbociclib + Aromatase Inhibitors (AI)
Sensitivity and Specificity of prediction of the efficacy of the combination (palbociclib +AI).
时间窗: From date of first treatment until the date of the first documented progression, assessed up to 2 years.
Sensitivity and specificity of infrared laser spectroscopy analysis on liquid biopsies to predict the efficacy/resistance of the combination (Palbociclib + Aromatase Inhibitors (AI)) on an individual basis.
次要结局
- Modification of the individual molecular fingerprinting(From the date of first treatment until the date of the first documented progression, assessed up to 2 years.)
- Prediction of progression in patients with initial response and objective clinical benefit(From the date of first treatment until the date of the first documented progression, assessed up to 2 years.)
- Prediction of progression in age-matched patients with initial response and objective clinical benefit(From the date of first treatment until the date of the first documented progression, assessed up to 2 years.)
- Number of patients with related adverse reactions(During the course of study treatment until progression, for an average duration of 2 years.)
- Prediction of Progression obtained from Raman spectroscopy(From the date of first treatment until the date of the first documented progression, assessed up to 2 years.)
- Prediction of early progression (>6 months).(During the course of study treatment, after M6 up to an average duration of 2 years.)
- Rate of Progression-Free Survival (PFS)(From Baseline to time of progression for an average duration of 2 years.)
- Rate of 'Objective' clinical benefit(From time CR/PR/Minor response [> 0%] up to more than 24 weeks)
- Rate of Clinical benefit(From time CR/PR/Stabilization up to more than 24 weeks)