Prediction of Treatment Efficacy of the Combination of Palbociclib/(Letrozole or Anastrozole) in First Line Metastatic Women With Luminal, HER2 Negative Advanced Breast Cancer, Using Infrared Laser Spectroscopy Analysis on Liquid Biopsies.

NCT05190094 | Recruiting Phase 2

• 1 other identifier: ICRG0201
• Study Type: interventional
• Target: 80
• Locations: 3 countries
• Sites: 7

Brief Summary

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".

Conditions

Hormonal Receptors Positive, HER2 Negative, Advanced Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Rate of Objective Clinical Response

  The objective clinical response will be assessed with Radiological evaluation according to the RECIST revised criteria for the combination of Palbociclib + Aromatase Inhibitors (AI)

  From date of first treatment until the date of the first documented progression, assessed up to 2 years.

• Sensitivity and Specificity of prediction of the efficacy of the combination (palbociclib +AI).

  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.

  From date of first treatment until the date of the first documented progression, assessed up to 2 years.

Secondary Outcomes (9)

• Rate of Progression-Free Survival (PFS)

  From Baseline to time of progression for an average duration of 2 years.

• Rate of Clinical benefit

  From time CR/PR/Stabilization up to more than 24 weeks

• Rate of 'Objective' clinical benefit

  From time CR/PR/Minor response [> 0%] up to more than 24 weeks

• 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.

Study Arms (1)

Palbociclib + Aromatase Inhibitors (AI) (Letrozole or Anatrozole)

EXPERIMENTAL

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.

Drug: Combination of Palbociclib and aromatase inhibitor (Letrozole or Anastrozole)

Interventions

Combination of Palbociclib and aromatase inhibitor (Letrozole or Anastrozole) DRUG

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).

Palbociclib + Aromatase Inhibitors (AI) (Letrozole or Anatrozole)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,

You may not qualify if:

• 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.
• 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.
• 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.

Sponsors & Collaborators

• International Cancer Research Group, United Arab Emirates: lead
• King Saud Medical City: collaborator
• Max-Planck-Institut für Quantenoptik (MPQ), and Faculty of Physics at Ludwig-Maximilians-Universität München (LMU), Garching, Germany: collaborator
• King Abdallah University for Science and Technology (KAUST), Thuwal, Saudi Arabia.: collaborator

Study Sites (7)

EHS LCC Blida, Medical Oncology Center

Blida, Algeria

NOT YET RECRUITING

University Hospital Sétif,

Sétif, Algeria

NOT YET RECRUITING

King Hussein Cancer Center (KHCC) - Amman

Amman, Jordan

RECRUITING

King Saud Medical City - KSMC

Riyadh, Saudi Arabia

NOT YET RECRUITING

Medical Oncology Center- King Saud University Medical City (KSUMC)

Riyadh, Saudi Arabia

NOT YET RECRUITING

Medical Oncology Department- King Fahad Medical City (KFMC)

Riyadh, Saudi Arabia

NOT YET RECRUITING

Oncology Center Department, King Faisal Specialist Hospital and Research Centre -KFSH & RC

Riyadh, Saudi Arabia

NOT YET RECRUITING

MeSH Terms

Interventions

Aromatase Inhibitors; Letrozole; Anastrozole

Intervention Hierarchy (Ancestors)

Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• M.R.K. BAHADOOR, MD, EMBA

  International Cancer Research Group

  STUDY DIRECTOR

Central Study Contacts

M.R.K. BAHADOOR, MD, EMBA

CONTACT

971586353489; mrkbahadoor@icrgrp.com

Farida DABOUZ, PhD

CONTACT

971564360008; farida.dabouz@icrgrp.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a multicenter, open-label study.

Study Record Dates

• First Submitted: December 8, 2021
• First Posted: January 13, 2022
• Study Start: December 20, 2022
• Primary Completion: December 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: May 7, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

SA (4); AL (2); JO (1)