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Study of palbociclib with hormone therapy guided by ESR1 mutation monitoring in patients with ER-positive, HER2-negative metastatic breast cancer

Verified siteRegistered drugNo placebo
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What is this trial about?

A plain-language summary of the goals, design and what participants do

This clinical trial focuses on patients with estrogen receptor-positive (ER+), HER2-negative metastatic breast cancer. The study examines the effectiveness and safety of a treatment combining palbociclib (a targeted therapy medication) with hormone therapy. The hormone therapy medications used in the study include letrozole, exemestane, anastrozole, and fulvestrant.

The main purpose of the study is to evaluate if changing hormone therapy based on detecting specific genetic changes in blood samples can improve treatment outcomes. The study monitors genetic changes in the ESR1 gene through blood tests. When these changes are detected, some patients will switch to a different combination of medications while others will continue their current treatment.

During the study, patients receive their assigned medications for 28-day treatment cycles. Palbociclib is taken as capsules by mouth, while most hormone therapies are taken as tablets. Fulvestrant is given as an injection. Patients undergo regular check-ups to monitor their health and how well the treatment is working. The study tracks how long patients remain without their disease getting worse and monitors any side effects, with special attention to effects on blood cell counts.

The research process

The trial runs in 3 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Initial treatment phase (Step 1)

    You will receive a combination of palbociclib (oral medication) and an aromatase inhibitor (oral medication - either letrozole, exemestane, or anastrozole) for breast cancer treatment

    Regular blood tests will monitor your organ function and blood cell counts

    Your doctor will perform tumor assessments using imaging methods to track treatment response

    Quality of life questionnaires need to be completed every 2 treatment cycles

  2. Step 2

    Monitoring phase (Step 2)

    Blood samples will be taken to check for specific genetic changes (ESR1 mutations) in your blood

    If these genetic changes are detected, and there are no signs of cancer progression on scans, you may be randomly assigned to either:

    Continue current treatment (Arm A): same combination of palbociclib and aromatase inhibitor

    Switch treatment (Arm B): change to fulvestrant (injection) while continuing palbociclib

  3. Step 3

    Follow-up phase (Step 3)

    If you were assigned to continue current treatment (Arm A) and your cancer shows progression on scans, you may switch to fulvestrant with palbociclib

    Regular assessments will continue to monitor your response to treatment

    Treatment will continue until either your disease progresses or you experience unacceptable side effects

    Quality of life questionnaires will continue every 2 cycles until disease progression or up to two years after starting the study

Who can join the trial?

12 criteria

  • Must be a woman aged 18 years or older
  • Must have breast cancer that is: - Estrogen Receptor-positive (at least 10% of cancer cells show positive ER staining) - HER2-negative - Has spread locally or to other parts of the body
  • Must be menopausal or have suppressed ovarian function
  • Must have adequate organ and blood function, including: - Hemoglobin levels ≥ 90 g/L - White blood cell count ≥ 1.5 G/L - Platelet count ≥ 100 G/L - Normal or near-normal liver and kidney function
  • Must have a life expectancy of more than 3 months
  • Must have an ECOG performance status of 0-2 (ability to perform daily activities)
  • Must not have received any previous systemic treatment for advanced disease (except hormone therapy for ovarian suppression or bone treatments)
  • Must have a tumor sample (either from primary tumor or metastasis) available for testing
  • Must be willing and able to: - Attend scheduled visits - Follow the treatment plan - Complete required laboratory tests - Comply with study procedures
  • Must have recovered from side effects of any previous cancer treatments
  • Must be affiliated with a social security system
  • Must provide written informed consent before starting any study procedures

Who cannot join the trial?

15 criteria

  • Prior treatment with any CDK4/6 inhibitor (medications that block specific proteins involved in cell growth)
  • Known active brain metastases (cancer that has spread to the brain) that are untreated or unstable
  • Major surgery within 2 weeks before starting the study treatment
  • Current treatment with medications that strongly affect certain liver enzymes (known as CYP3A4 inhibitors or inducers)
  • Severe heart conditions, including:
    • Uncontrolled high blood pressure
    • Unstable heart rhythm problems
    • Heart attack within the past 6 months
    • Active hepatitis B or C infection (liver infections)
    • Known HIV infection that is not well-controlled with medication
    • Other active cancers requiring treatment, except for adequately treated non-melanoma skin cancer or cervical cancer in situ
    • Severe liver problems or abnormal liver function tests
    • History of severe allergic reactions to study medications or their components
    • Pregnancy or breastfeeding
    • Unable or unwilling to swallow oral medications
    • Any condition that would make it unsafe to participate in the study or interfere with study procedures
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Investigated drugs

  • Palbociclib

    is a medication used to treat breast cancer. It works by blocking specific proteins that help cancer cells grow and divide. It's typically taken as a pill and is used in combination with hormone therapy to treat hormone receptor-positive, HER2-negative breast cancer.

  • Fulvestrant

    is a hormone therapy medication that blocks and degrades estrogen receptors in breast cancer cells. It's given as an injection and helps slow or stop the growth of hormone-sensitive breast cancer cells.

  • Aromatase inhibitors

    are a class of hormone therapy medications that work by lowering estrogen levels in the body. They do this by blocking an enzyme called aromatase, which is responsible for producing estrogen. These medications are commonly used to treat hormone receptor-positive breast cancer in postmenopausal women.

What is already known about the treatment

  • Palbociclib

    An oral medication used in the treatment of hormone receptor-positive (ER+), HER2-negative metastatic breast cancer, typically administered in combination with hormone therapy. This drug works by inhibiting specific proteins (CDK4/6) that promote cancer cell growth, effectively slowing down or stopping the progression of cancer cells. It belongs to the class of targeted cancer therapies known as CDK inhibitors and has shown significant effectiveness in clinical trials when combined with endocrine therapy.

  • Fulvestrant

    An injectable hormone therapy medication used in the treatment of hormone receptor-positive metastatic breast cancer, administered through intramuscular injection. This drug works by blocking and degrading estrogen receptors in cancer cells, preventing the stimulation of tumor growth by estrogen. It belongs to the class of medications known as estrogen receptor antagonists and is often used in combination with other targeted therapies, particularly when other hormone treatments become less effective.

Investigated diseases

ER+/HER2- Metastatic Breast Cancer - A type of breast cancer that has spread beyond the breast to other parts of the body (metastatic), characterized by the presence of estrogen receptors (ER+) and the absence of HER2 protein (HER2-) on cancer cells. This cancer grows in response to the hormone estrogen. The cancer cells have spread through the bloodstream or lymphatic system to create secondary tumors in other organs. The disease typically develops gradually, with cancer cells first growing in the breast tissue before spreading to other locations such as bones, liver, lungs, or brain. As the disease progresses, the cancer cells continue to multiply in their new locations while maintaining their original characteristics of being hormone-receptor-positive and HER2-negative.
Trial detailsLast updated 2 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2024-510704-37-00Protocol codeUC-0140/1615Estimated enrolment1 000 patientsSponsorUnicancer

sourced from the EU Clinical Trials Register and site verification

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