Not recruiting

Study of alpelisib with trastuzumab and pertuzumab as maintenance therapy in adult patients with HER2‑positive advanced breast cancer and PIK3CA mutation

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

The study focuses on HER2-positive advanced breast cancer, a form of breast cancer that has spread beyond the breast and shows high levels of a protein called HER2. Some of these cancers also carry a PIK3CA mutation, which is a small change in a gene that can make the cancer grow faster.

Participants receive a combination of medicines: an oral pill called alpelisib (code name BYL719) taken each day, together with two drugs, trastuzumab and pertuzumab, that are given through an intravenous infusion (a drip into a vein). A placebo, which looks like the active pills but contains no medicine, is used for comparison. The purpose of the trial is to find out whether adding alpelisib to the standard HER2‑targeted therapy can keep the cancer from getting worse for a longer time.

The study begins with a safety phase in which a small group receives the drug combination and doctors watch for serious side effects during the first several weeks. If the safety checks are satisfactory, participants move into the main phase where they are randomly assigned, without knowing which group they are in, to receive either the full drug combination or the placebo. They are then followed for several months, with regular check‑ups and scans, to see how long the cancer stays controlled and to monitor any side effects.

The research process

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

Step 1
Enrollment and baseline assessments
After joining the study, you will undergo tests to confirm her2-positive advanced breast cancer and the presence of a pik3ca mutation. these assessments include imaging, blood samples, and a review of medical history.
The results determine eligibility for the two‑part trial.
Step 2
Safety run‑in (part 1)
You will start receiving three medicines together:
alpelisib taken by mouth at a dose of 300 mg once each day;
trastuzumab given as an intravenous infusion at 6 mg per kilogram of body weight;
pertuzumab given as an intravenous infusion at a fixed dose of 420 mg.
This combination is administered for the first six weeks of treatment.
During these six weeks you will have regular clinic visits where doctors check for side effects called dose‑limiting toxicities, monitor blood work, and assess overall safety.
Step 3
Assessment after safety run‑in
At the end of week 6, investigators review safety data to confirm that the dose of alpelisib (300 mg daily) is appropriate to continue.
If the dose is confirmed, the trial proceeds to the next part.
Step 4
Double‑blind treatment (part 2)
You will be randomly assigned to receive either:
• alpelisib 300 mg orally each day, or
• a matching placebo taken orally each day.
In both groups you will continue to receive trastuzumab (6 mg/kg iv infusion) and pertuzumab (420 mg iv infusion) on the same schedule as in part 1.
Treatment continues until disease progression, unacceptable side effects, or withdrawal from the study.
Step 5
Ongoing monitoring during double‑blind phase
You will attend periodic visits for imaging tests, blood laboratory checks, and evaluation of any side effects.
Questionnaires may be completed to assess quality of life.
Dose adjustments or temporary interruptions of any medication may be made based on safety findings.
Step 6
End of treatment and follow‑up
When treatment stops, you will enter a follow‑up period during which survival and long‑term safety are observed.
Follow‑up visits are scheduled at regular intervals to collect final data.

Who can join the trial?

5 criteria

You must have breast cancer that has been confirmed by a tissue test and is classified as HER2‑positive, and the cancer must be advanced – meaning it has come back in the same area and cannot be removed by surgery, or it has spread to other parts of the body.
You need to have already received initial (induction) treatment that included up to 8 cycles of a chemotherapy drug called a taxane (such as docetaxel, paclitaxel, or nab‑paclitaxel) together with the targeted medicines trastuzumab and pertuzumab. If you stopped the taxane early because of side effects, you must have had at least 4 cycles.
Your overall health must be good enough to allow you to walk around and do normal activities, measured by an ECOG performance status of 0 (fully active) or 1 (restricted in physically strenuous activity but able to do light work).
Your blood‑forming (bone marrow) system and major organs (like liver and kidneys) must be working well enough, which is called “adequate bone marrow and organ function.”
For the second part of the study, you must have a specific genetic change called a PIK3CA mutation in your tumor tissue, which will be confirmed by a special laboratory.

Who cannot join the trial?

7 criteria

Having inflammatory breast cancer at the time of screening, which is a fast‑growing, red and swollen form of breast cancer.
Having disease that got worse during or after the initial treatment given before the study (called pre‑study induction therapy) before the first dose of the study medication.
Having type I diabetes or type II diabetes that is not well‑controlled, as shown by high fasting plasma glucose (blood sugar after not eating) or high HbA1c (a test that shows average blood sugar over the past few months).
Having had a sudden inflammation of the pancreas (acute pancreatitis) within the past year, or a long‑lasting pancreas inflammation (chronic pancreatitis).
Having serious heart disease that is not under control, or having had a recent heart problem such as a heart attack or severe irregular heartbeat (recent cardiac events).
Having a past severe skin reaction such as Steven‑Johnson Syndrome, erythema multiforme, Toxic Epidermal Necrolysis, or Drug Reaction with Eosinophilia and Systemic Syndrome.
Having current lung inflammation (pneumonitis) or scarring of the lung tissue (interstitial lung disease).

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Verified sites

All sites with verified contact details – recruitment status may not be available; ask directly

Centre Hospitalier Lyon Sud
Verified
Pierre Benite, France
Centre Leon Berard
Verified
Lyon, France
Comite Entreprise Paul Papin
Verified
Angers, France

Trial locations

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Investigated drugs

Alpelisib
is an oral medication that targets a specific pathway inside cancer cells. In this study it is given together with two other drugs to see if it can help keep HER2‑positive advanced breast cancer under control after initial treatment. The goal is to find out whether adding alpelisib can improve the time patients live without the cancer getting worse.
Trastuzumab
is a medicine given by IV infusion that attaches to the HER2 protein on the surface of some breast cancer cells. By binding to HER2, it helps the immune system recognize and attack the cancer. In this trial trastuzumab is used as part of a combination therapy to maintain disease control.
Pertuzumab
is also an IV infusion drug that works alongside trastuzumab. It binds to a different part of the HER2 protein, providing a stronger block of the signals that make cancer grow. In the study, pertuzumab is combined with trastuzumab and alpelisib to see if the three‑drug mix can keep the cancer from progressing for a longer time.

What is already known about the treatment

Alpelisib
Alpelisib is taken as an oral tablet, usually 300 mg once daily. It is an approved drug for certain breast cancers that have a PIK3CA mutation and is now being studied as maintenance therapy for HER2‑positive advanced breast cancer. The medicine works by selectively blocking the PI3K‑α enzyme, which stops signals that tell cancer cells to grow and survive. Alpelisib belongs to the class of PI3K inhibitors, a type of targeted therapy.
Trastuzumab
Trastuzumab is given by intravenous infusion, typically at a dose of 6 mg per kilogram of body weight. It is an approved treatment for HER2‑positive breast cancer and is widely used in clinical practice. The drug is a monoclonal antibody that attaches to the HER2 protein on cancer cells, blocking growth signals and marking the cells for attack by the immune system. Trastuzumab is classified as a HER2‑targeted monoclonal antibody.
Pertuzumab
Pertuzumab is administered by intravenous infusion, commonly as a 420 mg dose. It is approved for use together with trastuzumab in HER2‑positive breast cancer. Pertuzumab binds to a different part of the HER2 receptor, preventing it from pairing with other receptors and thereby stopping growth signals. It is also a HER2‑targeted monoclonal antibody.

Investigated diseases

HER2-positive advanced breast cancer - HER2-positive advanced breast cancer is a type of breast cancer that has high levels of the HER2 protein on the surface of its cells. The disease starts in the breast tissue and then spreads beyond the breast to other parts of the body, such as lymph nodes, bones, liver, or lungs. As it progresses, the cancer cells continue to grow and form new tumors in these distant sites. The condition is considered advanced when it cannot be removed by surgery alone.