Predicting treatment response in advanced breast cancer using liquid biopsies

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 testing a new combination treatment for women with advanced breast cancer to see if using blood tests can help predict how well they will respond to the therapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: International Cancer Research Group, United Arab Emirates (Academic / other)
• Locations: 7 sites (Blida and 6 other locations)
• Trial ID: NCT05190094 on ClinicalTrials.gov

What this trial studies

This multicenter, international phase II study aims to evaluate the efficacy of a combination therapy using Palbociclib and aromatase inhibitors (Letrozole or Anastrozole) in women with newly diagnosed metastatic luminal hormone receptor-positive and HER2 negative breast cancer. Eligible patients will undergo treatment while their responses are monitored through clinical and radiological assessments every three months. The study uniquely incorporates Quantum Optics technology for plasma molecular fingerprinting via liquid biopsies to predict individual treatment responses, potentially allowing for more personalized therapy. The primary objective is to assess the rate of clinical response and the predictive value of the molecular profiles obtained from the liquid biopsies.

Who should consider this trial

Good fit: Ideal candidates include pre and postmenopausal women with newly diagnosed metastatic luminal hormone receptor-positive and HER2 negative breast cancer.

Not a fit: Patients with non-luminal or HER2 positive breast cancer, or those who have received prior systemic treatment for advanced disease, may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to more personalized treatment strategies for women with advanced breast cancer, improving response rates and minimizing unnecessary treatments.

How similar studies have performed: While the use of liquid biopsies in cancer treatment is gaining traction, this specific approach utilizing Quantum Optics technology for predictive analysis is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

To be enrolled in the study, patients should meet the following inclusion criteria:

1. 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.
2. Postmenopausal women or pre/peri-menopausal women with Surgical oophorectomy (preferred) or Analogs of LHRH.
3. Performance status \< 3 (according to WHO criteria).
4. Histologically confirmed breast cancer (Luminal A or B).
5. Estrogen Receptor positive (ER \> 1%).
6. HER2 negative (score 0 or 1 by immunochemistry), FISH negative if IHC score 2.
7. Clinical stage IIIb \& IV.
8. Either:

   1. Women with De novo advanced luminal HER2 negative advanced breast cancer without other prior systemic treatment for advanced disease.
   2. 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).
9. Measurable or evaluable disease.
10. Hematology:

    * Neutrophil count ≥ 1.5 G/L,
    * Platelet count ≥ 100 G/L,
    * Leucocyte count \> 3.0 G/L,
    * Hb\> 9g/dl.
11. 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).
12. Renal function:

    • Serum creatinine ≤1.5xUNL (and if Serum creatinine \>1.5xUNL, creatinine clearance ≥40 mL/min),
13. Metabolic function:

    • Serum calcium ≥ lower limit of normal.
14. 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.
15. Patients with negative Human Immunodeficiency Virus (HIV) and/or Hepatitis B and/or Hepatitis C results.

Exclusion Criteria:

To be enrolled in the study, patients should meet the following exclusion criteria:

1. Male patients.
2. HER2 positive tumors or unknown HR/HER2 status.
3. Triple-negative Breast Cancer (ER\<1%).
4. Pregnant or breast-feeding women, or those who plan to become pregnant within 6 months post-treatment.
5. No willingness to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months post-treatment.
6. Any form of breast cancer other than those described in the inclusion criteria, particularly inflammatory and/or loco-regional disease (stages I, II \& IIIa).
7. Non-evaluable tumor.
8. Bilateral breast cancer.
9. Patients with a history of other cancer, except in situ cervical cancer or baso-cellular skin cancer, considered cured.
10. Patient has another disease, which is deemed incompatible with the inclusion in the protocol.
11. 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.
12. Uncontrolled diabetes.
13. Symptomatic or progressive disorder of the central nervous system (CNS) at baseline.
14. Patients with positive Human Immunodeficiency Virus (HIV) and/or Hepatitis B and/or Hepatitis C results.
15. Significant psychiatric abnormalities.
16. History of hypersensitivity to studied treatment or excipients.
17. Known previous or ongoing abuse of narcotic drug, other medication or alcohol.
18. Any investigational agent within 30 days before initiation of study treatment.
19. Patient unwilling or unable to comply with study requirements.

Where this trial is running

Blida and 6 other locations

• 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)

Study contacts

• Study coordinator: M.r.k. Bahadoor, Md, Emba

Conditions Hormonal Receptors Positive, HER2 Negative, Advanced Breast Cancer