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Study on Alpelisib and Fulvestrant or Ribociclib and Fulvestrant for Patients with HR+, HER2- Metastatic Breast Cancer with PIK3CA Mutations

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 is focused on studying a type of breast cancer known as metastatic breast cancer that is hormone receptor-positive (HR+) and does not express HER2. The study aims to explore the effectiveness of different treatment combinations for patients with specific genetic changes called PIK3CA mutations. These mutations are detected in the blood after patients have been treated with a type of medication called a CDK4/6 inhibitor, which is used in combination with another drug called fulvestrant.

The trial will compare two treatment combinations: one using alpelisib with fulvestrant, and the other using ribociclib with fulvestrant. Alpelisib is a medication that targets a specific protein involved in cancer cell growth, while ribociclib is another type of CDK4/6 inhibitor. Fulvestrant is a drug that blocks the effects of estrogen, a hormone that can promote the growth of breast cancer cells. The purpose of the study is to determine which combination is more effective in delaying the progression of the disease.

Participants in the study will receive one of these treatment combinations and will be monitored over time to assess how well the treatment is working. The study will also look at the overall survival of participants and any side effects they may experience. This research is important for understanding how to best treat patients with this type of breast cancer and specific genetic mutations.

The research process

The trial runs in 6 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Joining the study

    Upon joining the study, you will be required to sign a written informed consent form. This form confirms your understanding and agreement to participate in the study.

    You will undergo initial assessments to ensure you have adequate bone marrow and organ function, and that you meet other eligibility criteria.

  2. Step 2

    Screening program

    During the screening phase, your medical history will be reviewed, and tests will be conducted to confirm your diagnosis of metastatic breast cancer HR+, HER2-.

    A blood test will be performed to detect tumor DNA in your blood, which helps in identifying patients who may benefit from further treatment.

  3. Step 3

    Initial treatment

    You will receive a combination of a CDK4/6 inhibitor and fulvestrant for four weeks. This is a standard treatment for your condition.

    The CDK4/6 inhibitor can be one of the following: palbociclib, ribociclib, or abemaciclib, administered orally. Fulvestrant is given as an intramuscular injection.

  4. Step 4

    Randomization

    After four weeks of initial treatment, a blood test will be conducted to check for persistent mutations in the PIK3CA gene.

    If mutations are detected, you will be randomly assigned to one of two treatment groups: alpelisib combined with fulvestrant or ribociclib combined with fulvestrant.

  5. Step 5

    Treatment phase

    If you are assigned to the alpelisib-fulvestrant group, you will take alpelisib orally and receive fulvestrant as an intramuscular injection.

    If you are assigned to the ribociclib-fulvestrant group, you will take ribociclib orally and receive fulvestrant as an intramuscular injection.

    The treatment will continue as per the study protocol, with regular monitoring and assessments to evaluate your response.

  6. Step 6

    Follow-up and monitoring

    Throughout the study, you will have scheduled visits for monitoring your health and the effectiveness of the treatment.

    Regular laboratory tests and other procedures will be conducted to ensure your safety and to track the progress of your condition.

Who can join the trial?

18 criteria

  • Patient must have signed a written informed consent before any study-specific procedures.
  • Patient must be at least 18 years old.
  • Patient must have a confirmed diagnosis of metastatic breast cancer.
  • Patient must have HER2-negative breast cancer. HER2 is a protein that can affect the growth of cancer cells.
  • Patient must have hormone receptor-positive (HR+) breast cancer, meaning the cancer cells have receptors for hormones like estrogen or progesterone.
  • Patient must have had a metastatic relapse during or within 1 year after stopping adjuvant endocrine therapy.
  • Patient must not have been treated yet for metastatic breast cancer.
  • Patient must be eligible for first-line treatment with a CDK4/6 inhibitor (such as palbociclib, ribociclib, or abemaciclib) combined with fulvestrant.
  • Patient must have adequate bone marrow and organ function, meaning their blood and organs are working well enough to participate.
  • Patient must have a persistent mutation on exon 4, 9, or 20 of the PIK3CA gene, determined by a blood test after 4 weeks of treatment with a CDK4/6 inhibitor and fulvestrant.
  • Patient must have stopped taking any CDK4/6 inhibitor at least 7 days before starting the study.
  • Patient must have an ECOG performance status of 0 or 1, which means they are fully active or have some symptoms but do not need bed rest.
  • Patient's life expectancy must be at least 3 months.
  • Patient must have certain laboratory values within normal limits, including a QTcF interval of less than 450ms and a resting heart rate between 50-90 beats per minute.
  • Women of childbearing potential must have a negative pregnancy test within 14 days before joining the study.
  • Men and women of childbearing potential must agree to use effective contraception during the study and for a specified time after the last dose of study treatment.
  • Patient must be willing and able to follow the study protocol, including attending scheduled visits and undergoing tests and procedures.
  • Patient must be affiliated with national social security or an equivalent system.

Who cannot join the trial?

6 criteria

  • Patients who do not have **Metastatic Breast Cancer HR+, HER2-**. This means the cancer has spread to other parts of the body, is hormone receptor-positive, and does not have too much of the HER2 protein.
  • Patients who do not have persistent mutations on exon 4, 9, or 20 of **PIK3CA ctDNA**. This refers to specific changes in the DNA that are still present after treatment.
  • Patients who have not been treated with any **CDK4/6 inhibitor-fulvestrant** in the first-line setting. This is a type of medication used to treat breast cancer.
  • Patients who are not within the specified age range for the study.
  • Patients who are not male or female, as the study includes both genders.
  • Patients who are part of a vulnerable population that the study does not include.
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Investigated drugs

  • Alpelisib

    is a medication used in this trial to treat certain types of breast cancer. It works by blocking a specific protein in the body that helps cancer cells grow. By stopping this protein, alpelisib can help slow down or stop the growth of cancer cells. In this study, it is combined with another medication to see if it can help patients with a specific genetic mutation in their cancer.

  • Fulvestrant

    is a therapy used to treat breast cancer by blocking the effects of estrogen, a hormone that can promote the growth of cancer cells. It is often used in patients whose cancer has spread to other parts of the body. In this trial, fulvestrant is combined with other medications to see if it can improve treatment outcomes for patients with certain genetic mutations.

  • Ribociclib

    is a medication that helps treat breast cancer by interfering with proteins that control cell division. By doing this, it can slow down or stop the growth of cancer cells. In this study, ribociclib is used alongside another medication to determine if it can be more effective for patients with specific genetic changes in their cancer.

What is already known about the treatment

  • Alpelisib

    Alpelisib is administered orally in tablet form and is currently being studied for its effectiveness in treating metastatic breast cancer that is hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-). It is used in combination with fulvestrant, a hormone therapy, to target specific genetic mutations in cancer cells. Alpelisib works by inhibiting a protein called PI3K, which is involved in the growth and survival of cancer cells. It is classified as a PI3K inhibitor and is being evaluated for its potential to improve progression-free survival in patients with certain genetic mutations.

  • Ribociclib

    Ribociclib is an oral medication taken in tablet form and is being investigated for its role in treating metastatic breast cancer that is HR+ and HER2-. It is used alongside fulvestrant to address persistent genetic mutations in cancer patients. Ribociclib functions by inhibiting proteins known as CDK4 and CDK6, which are crucial for cancer cell division and growth. This medication is classified as a CDK4/6 inhibitor and is being studied to determine its effectiveness in extending progression-free survival in patients with specific genetic profiles.

Investigated diseases

Metastatic Breast Cancer HR+, HER2- – This type of breast cancer is characterized by the spread of cancer cells beyond the breast to other parts of the body. It is hormone receptor-positive (HR+), meaning the cancer cells grow in response to hormones like estrogen or progesterone. The cancer is also HER2-negative, indicating it does not have an excess of the HER2 protein on its surface. The progression involves the cancer cells traveling through the bloodstream or lymphatic system to form new tumors in other organs. Over time, these metastatic tumors can affect the function of the organs they invade. The disease can progress at varying rates, depending on factors like the location of metastases and the biology of the cancer cells.
Trial detailsLast updated 2 Oct 2026
Age18+ yearsPhasePhase IITrial ID2022-502372-22-01Protocol codeUC-GMP-2206Estimated enrolment1 080 patientsSponsorUnicancer

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