Hormonal Receptors Positive, HER2 Negative, Advanced Breast CancerPhase 2ICRG0201NCT05190094
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.
A Phase 2 study testing Combination of Palbociclib and aromatase inhibitor (Letrozole or Anastrozole) in people with Hormonal Receptors Positive, HER2 Negative, Advanced Breast Cancer, run by International Cancer Research Group, United Arab Emirates at 7 sites in 3 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Hormonal Receptors Positive, HER2 Negative, Advanced Breast Cancer
- What is being tested?
- Combination of Palbociclib and aromatase inhibitor (Letrozole or Anastrozole)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 7 sitesin 3 countries
- Study dates
- 20 Dec 2022to Jun 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%).
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
7 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
7 sites in 3 countries
Saudi Arabia4 sites, 4 recruiting
- Not yet recruiting
King Saud Medical City - KSMC
Riyadh
Soad Hakamy
Ashraf Aly, MD
- Not yet recruiting
Medical Oncology Center- King Saud University Medical City (KSUMC)
Riyadh
Isam Almasri
Muath Abuhilal
- Not yet recruiting
Medical Oncology Department- King Fahad Medical City (KFMC)
Riyadh
Bassam Basulaiman, MD
- Not yet recruiting
Oncology Center Department, King Faisal Specialist Hospital and Research Centre -KFSH & RC
Riyadh
Leilani Cabangon
Taher Twegieri, MD
Algeria2 sites, 2 recruiting
- Not yet recruiting
EHS LCC Blida, Medical Oncology Center
Blida
Zoubir DERBOUZ, MD
Adda BOUNEDJAR, MD, Prof.
- Not yet recruiting
University Hospital Sétif,
Sétif
Adlane Dib, MD, Prof
Jordan1 site, 1 recruiting
- Recruiting
King Hussein Cancer Center (KHCC) - Amman
Amman
Farah Zahran
Abdelrahman Barhoum
About this study
Official title: 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".
Read the detailed description
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.
Secondary:
- Progression-Free Survival (PFS).
- Clinical benefit (CR/PR/Stabilization>24 weeks).
- 'Objective' clinical benefit (CR/PR/Minor response (> 0% > 24 weeks).
- Modification of the individual molecular fingerprinting during treatment.
- Role of individualized molecular fingerprinting to predict early progression (>6 months).
- Role of individualized molecular fingerprinting to predict relapse in age-matched patients with an initial response.
- Safety and tolerability of the proposed regimen.
- Benchmark analysis, using Raman Spectroscopy.
Materials and Methods:
Study design:
This study is a multicenter, international, open-label phase II study. Based on inclusion/exclusion criteria, eligible pre and post-menopausal patients with newly diagnosed metastatic Luminal HER2 negative breast cancer, will be prospectively treated with a standard combination of HT (AI: 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 liquid biopsies (blood tests) for plasma molecular fingerprinting by the QO technology at enrolment, each month for the first three months and then every three months until relapse, along with clinical and radiological assessments every three months.
Sample size: Considering the approximately 50% response rate (RR) previously reported in the phase III PALOMA 2 trial (AI + Palbociclib) and the initial published data of QO analysis on liquid biopsies, which compared plasma molecular fingerprint profiles between a control population without breast cancer and a population with breast cancer (sensitivity: 98% / specificity: 97%), we hypothesize that the sensitivity to differentiate responders to non-responders by QO analysis on liquid biopsies (prediction of efficacy) will be 97%. Based on the above hypothesis, the sample size calculated using alpha 5% and power 95% is N=80 patients to be enrolled and treated.
Populations:
The Intent-to-Treat (ITT): all patients enrolled in the study. The safety population: all patients receiving any treatment.
Statistical Methodology:
Qualitative variables are frequency and percentage. Comparison of the proportion between responders and non-responders will use the chi-square test.
Quantitative variables: mean, standard deviation, median, maximum, and minimum. Time-dependent parameters: Kaplan-Meier method. Cox's proportional hazards regression analysis for response rates, clinical benefits, PFS.
All tests of hypotheses: one-sided. Confidence intervals of the median survival: method of Simon.
The methodology of computational analysis: "non-hierarchical deep data mining" approach with:
- Analyses with the support vector machines with a polynomial nucleus.
- Age stratifications when applicable with sub-stratifications in different age groups.
- Being tested
- Combination of Palbociclib and aromatase inhibitor (Letrozole or Anastrozole)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Combination of Palbociclib and aromatase inhibitor (Letrozole or Anastrozole) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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.
Measured: 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)
Progression-Free Survival (PFS)
Measured: From Baseline to time of progression for an average duration of 2 years.
Rate of Clinical benefit
Clinical benefit is defined as CR/PR/Stabilization for more than 24 weeks
Measured: From time CR/PR/Stabilization up to more than 24 weeks
Rate of 'Objective' clinical benefit
'Objective' clinical benefit is defined as CR/PR/Minor response [> 0%] more than 24 weeks).
Measured: From time CR/PR/Minor response [> 0%] up to more than 24 weeks
Modification of the individual molecular fingerprinting
Modification of the individual molecular fingerprinting
Measured: 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
Modification of individualized molecular fingerprinting will be used to predict progression
Measured: 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
Modification of individualized molecular fingerprinting will be used to predict progression
Measured: 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).
Modification of individualized molecular fingerprinting will be used to predict early progression (>6 months).
Measured: During the course of study treatment, after M6 up to an average duration of 2 years.
Number of patients with related adverse reactions
Adverse events will be collected during the course of the study. Relationship to study drug is also reported.
Measured: During the course of study treatment until progression, for an average duration of 2 years.
Prediction of Progression obtained from Raman spectroscopy
Modification of individualized molecular fingerprinting will be used to predict progression obtained from Raman spectroscopy as a benchmark analysis
Measured: From the date of first treatment until the date of the first documented progression, assessed up to 2 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2022
- Study start20 Dec 2022
- Primary completionDec 2025 (estimated)
- Study completionJun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hormonal Receptors Positive, HER2 Negative, Advanced Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a multicenter, open-label study.
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- International Cancer Research Group, United Arab Emirates
- Sponsor type
- University, hospital or other
- Collaborators
- King Saud Medical City, Max-Planck-Institut für Quantenoptik (MPQ), and Faculty of Physics at Ludwig-Maximilians-Universität München (LMU), Garching, Germany, King Abdallah University for Science and Technology (KAUST), Thuwal, Saudi Arabia.
- Responsible party
- Sponsor
- Investigators
- M.R.K. BAHADOOR, MD, EMBA, Study director, International Cancer Research Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05190094
- Sponsor's protocol ID
- ICRG0201
- Acronym
- ICRG0201
- Status last verified
- Mar 2025
- First submitted
- 8 Dec 2021
- Last updated
- 7 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No