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).
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.
• 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 2.
• Clinical stage IIIb \& IV.
• Either:
∙ 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.