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Study Comparing Two Treatment Sequences of CDK4/6 Inhibitors (Abemaciclib, Palbociclib, or Ribociclib) in Hormone Receptor Positive Advanced 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 studies treatments for hormone receptor-positive breast cancer that has spread to other parts of the body (advanced or metastatic). The study compares two different treatment strategies using medications called CDK4/6 inhibitors (including abemaciclib, palbociclib, and ribociclib) combined with hormone therapy. These medications work by blocking proteins that help cancer cells grow.

The main purpose is to determine which treatment sequence works better: using a CDK4/6 inhibitor with hormone therapy first, followed by fulvestrant alone when the disease progresses; or starting with hormone therapy alone, followed by fulvestrant combined with a CDK4/6 inhibitor when the disease progresses. Additional hormone therapies that may be used include anastrozole, letrozole, goserelin, and leuprorelin.

During the study, patients will receive treatment until their disease progresses or they cannot tolerate the medication. The researchers will monitor how long it takes for the cancer to progress after both first and second treatments, overall survival, quality of life, and side effects. They will also collect tumor samples and blood tests to study markers that might help predict which patients respond best to treatment.

The research process

The trial runs in 4 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
Initial treatment phase - Strategy A or B
You will be assigned to one of two treatment strategies:
Strategy A: You will receive a non-steroidal aromatase inhibitor combined with CDK4/6 inhibitor tablets as first treatment
Strategy B: You will receive only a non-steroidal aromatase inhibitor tablets as first treatment
If you are not in post-menopause, you will also receive hormone therapy to suppress ovarian function
Step 2
Regular medical evaluations
Your health status will be regularly monitored through blood tests and imaging
Your doctor will assess how well the treatment is working
Side effects will be monitored and recorded
Quality of life assessments will be conducted
Step 3
Second treatment phase
If the disease progresses during the first treatment:
Strategy A: You will receive fulvestrant alone
Strategy B: You will receive fulvestrant combined with CDK4/6 inhibitor tablets
Regular monitoring will continue as in the previous phase
Step 4
Additional assessments
Blood samples will be collected to analyze tumor DNA
Imaging scans will be performed to evaluate treatment response
Cognitive function will be assessed through online tests
The study will continue until December 2028

Who can join the trial?

12 criteria

Must be a female adult aged 18 or older
Must have breast cancer that has spread locally or to other parts of the body (metastatic) that cannot be treated with surgery or radiation therapy with the aim of cure
Must have breast cancer that tests positive for certain hormones (estrogen receptor >10% and/or progesterone receptor >10%) and negative for HER2 protein
Must not have received any previous systemic treatment for metastatic breast cancer, except for hormone therapy started within the last 28 days
If not post-menopausal, must be willing to receive treatment to stop ovarian function
Must have cancer that can be measured using standard imaging techniques
Must have a good general health status (ECOG performance status of 0-2, meaning able to perform most daily activities)
Must have adequate organ function, including:
- Sufficient white blood cell counts
- Sufficient platelet counts
- Adequate kidney function
- Acceptable liver function
- Must have recovered from side effects of any previous cancer treatments, with most side effects resolved or mild (except for hair loss)

Who cannot join the trial?

14 criteria

Previous systemic treatment for metastatic breast cancer
Male patients (study is for females only)
Age below 18 years
Known HER2-positive breast cancer (where cancer cells have too much of a protein called HER2 on their surface)
Known hormone receptor-negative breast cancer (cancer cells that do not have receptors for estrogen or progesterone)
Prior treatment with CDK4/6 inhibitors (medications that block specific proteins involved in cell growth)
Prior treatment with aromatase inhibitors (medications that lower estrogen levels) for metastatic disease
Prior treatment with fulvestrant (a hormone therapy that blocks estrogen receptors)
Active or untreated brain metastases (cancer that has spread to the brain)
Pregnancy or breastfeeding
Serious heart conditions or uncontrolled high blood pressure
Severe liver or kidney problems
Active serious infections
Other active cancers requiring treatment

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Verified sites

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Amsterdam UMC
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Amsterdam, The Netherlands
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
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Rotterdam, The Netherlands
Leids Universitair Medisch Centrum (LUMC)
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Leiden, The Netherlands

Trial locations

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Investigated drugs

Non-steroidal aromatase inhibitors
are medications that lower estrogen levels in the body. They work by blocking an enzyme called aromatase, which helps produce estrogen. These medications are commonly used to treat hormone receptor-positive breast cancer.
CDK4/6 inhibitors
are targeted therapy medications that work by blocking specific proteins called CDK4 and CDK6, which help cancer cells grow and divide. These medications are used in combination with hormone therapy to treat hormone receptor-positive breast cancer.
Fulvestrant
is a hormone therapy medication that blocks and degrades estrogen receptors in cancer cells. It works differently from aromatase inhibitors and is often used when breast cancer has progressed after other hormone treatments. It's given as an injection and helps slow down or stop the growth of hormone receptor-positive breast cancer.

What is already known about the treatment

CDK4/6 inhibitors
A class of targeted cancer therapy medications administered orally that work by blocking specific proteins called cyclin-dependent kinases 4 and 6, which are involved in cell division. These drugs are primarily used in the treatment of hormone receptor-positive (HR+) advanced breast cancer in combination with hormone therapy. The medication works by preventing cancer cells from multiplying by interrupting their cell division cycle at the molecular level, effectively slowing down or stopping tumor growth. These inhibitors represent a significant advancement in breast cancer treatment, particularly for metastatic cases, and are classified as targeted therapy agents in the pharmacological system.
Fulvestrant
An injectable hormone therapy medication administered via intramuscular injection that works as a selective estrogen receptor degrader (SERD). It is specifically used in the treatment of hormone receptor-positive advanced breast cancer in postmenopausal women, particularly when other hormonal treatments have stopped working. The medication functions by binding to and degrading estrogen receptors, thereby blocking the effects of estrogen that can stimulate cancer cell growth. In clinical practice, it is classified as an antiestrogen medication and is often used as a second-line treatment option.
Aromatase inhibitors (non-steroidal)
Oral medications that work by blocking the enzyme aromatase, which is responsible for producing estrogen in postmenopausal women. These drugs are used as a first-line treatment for hormone receptor-positive breast cancer in postmenopausal women, helping to reduce the amount of estrogen in the body and thereby slowing or stopping the growth of estrogen-dependent breast cancer cells. They belong to the class of hormone therapy drugs and are considered a cornerstone of breast cancer treatment, particularly in the advanced or metastatic setting.

Investigated diseases

Breast Cancer - A disease that begins when cells in the breast tissue start to grow out of control. It typically starts in either the ducts that carry milk to the nipple or the glands that make breast milk. As the cancer cells multiply, they can form a tumor that can often be felt as a lump or seen on an x-ray. The cancer cells can spread into surrounding breast tissue and potentially to other parts of the body. This disease can occur in both women and men, though it's much more common in women. Breast cancer may be influenced by various factors including genetic, hormonal, and environmental components.