A study looking at palbociclib, letrozole, trastuzumab and tucatinib before surgery for breast cancer (3-Pillars Study)
Cancer type:
Status:
Phase:
This study is looking at palbociclib, letrozole, trastuzumab and tucatinib before surgery for women with a newly diagnosed breast cancer.
It is open to women whose breast cancer has:
- receptors for the oestrogen and progesterone hormones (
hormone receptor positive )
- a large number of the human epidermal growth factor receptor (
HER2 positive )
More about this trial
One of the main treatments for breast cancer is surgery. Before surgery you might have other treatments such as or
. This is called neo adjuvant treatment.
Doctors use neo adjuvant treatment to:
- shrink the cancer size before surgery
- reduce the risk of the cancer coming back after surgery
In this study, researchers are looking at neo adjuvant treatment for post menopausal women with breast cancer that is hormone receptor positive and HER2 positive. They are looking at the drugs:
- palbociclib
- letrozole
- trastuzumab
- tucatinib
Palbociclib is a called a cancer growth blocker. It works by blocking 2 proteins on the cancer cells. By blocking these proteins, it can slow down or stop the cancer cells from growing. Doctors already use palbociclib to treat breast cancer that has spread.
Letrozole is a hormone therapy. It works by lowering the level of the hormone oestrogen in the body. Oestrogen stimulates hormone receptor positive breast cancers to grow. By lowering the level of oestrogen, letrozole can slow down or stop the breast cancer growing. Doctors already use letrozole as a treatment for post menopausal women with breast cancer.
Trastuzumab is a targeted drug called a monoclonal antibody. It blocks a protein called . Cancer cells need HER2 to grow and divide. By blocking HER2, trastuzumab can slow down or stop the cancer from growing. Some breast cancers have a large number of the HER2 protein. These are called HER2 positive breast cancers. Doctors already use trastuzumab to treat HER2 positive breast cancers.
Tucatinib is a called a tyrosine kinase inhibitor (TKI). Tyrosine kinases are proteins that cells use to signal to each other to grow. They act as chemical messengers. Blocking these signals helps to slow or stop the cancer from growing. Doctors already use tucatinib as a treatment in combination with other drugs to treat breast cancer that has spread.
Researchers think that having these 4 drugs before surgery might help post menopausal women with breast cancer.
To find this out, everyone in this study will have a with all 4 drugs before their surgery.
The aims of the study are to find out:
- how well this combination of treatment works
- about the side effects of having these drugs together
- how acceptable the treatment is to the women taking part
Who can enter
The following bullet points are a summary of the entry conditions for this study. Talk to your doctor or the study team if you are unsure about any of these. They will be able to advise you.
Who can take part
You may be able to join this study if you are a woman who has gone through the menopause (post menopausal) and all of the following apply.
- You are newly diagnosed with
early breast cancer .
- You have had an ultrasound scan,
mammogram or an
MRI scan that shows the cancer is at least 15mm across. If the scan shows that the cancer has gone to the
lymph nodes in the armpit then the cancer can be any size. Your doctor can say whether this applies to you.
- Your cancer is hormone receptor positive for oestrogen and progesterone and it has a large number of the
HER2 receptor (HER2 positive).
- You had a tissue sample (
biopsy ) taken when you were diagnosed that the team can use.
- You have satisfactory blood test results.
- You are up and about, can look after yourself but might not be able to work (performance status 0, 1 or 2).
- You are able to swallow tablets.
- Your heart works well enough. You have a test to find this out.
- You are at least 18 years old.
Who can’t take part
Cancer related
You cannot join this study if any of these apply. You:
- have inflammatory breast cancer or cancer that cannot be removed by surgery
- have
invasive cancer in both breasts
- have cancer that has spread to another part of the body
- have had another similar drug to the ones used in the trial. Your doctor will know this.
- have had treatment that targets the
HER2 protein
- have had another cancer within the past 5 years unless there is a low risk of it coming back. You can join if you had successfully treated
non melanoma skin cancer or
carcinoma in situ of the cervix. Or if you had surgery only to treat your cancer.
Medical conditions
You cannot join this study if any of these apply. You:
- are taking
hormone replacement therapy (HRT) , or any other medication or supplement that contains
oestrogen , within 12 weeks of joining the study
- are taking medication, supplements or herbal preparations that affect the
CYP enzymes within 1 or 2 weeks of starting treatment. You must not start taking any of these during treatment. Or you must not have any foods or drinks that affect the CYP enzymes. Your doctor can tell you more about this.
- have taken an experimental drug as part of a clinical trial within 4 weeks of joining the study
- have certain
heart problems . Your doctor will know about this.
- have
digestive problems . Your doctor will know about this.
- have a problem with bleeding
- have HIV, hepatitis B, hepatitis C, an active bacterial infection or fungal infection
Other
You cannot join this study if either of these apply. You:
- have a
live vaccine within 28 days of joining the study
- are allergic or sensitive to the treatments or any of their ingredients
Trial design
This is a phase 2 study. The team need 90 women to take part.
Before surgery everyone has:
- palbociclib
- letrozole
- trastuzumab
- tucatinib
Palbociclib is a tablet. You take it once a day everyday for 3 weeks. Then you have a week of not taking it. Do not chew or crush the tablets. You should take them at the same time each day and preferably with food. Your doctor will tell you how many tablets to take.
Letrozole is a tablet. You take it once a day every day. Do not chew or crush the tablets. You should take them at the same time each day and preferably with food. Your doctor will tell you how many tablets to take.
You have trastuzumab as an injection under the skin. You have it once every 3 weeks. You go to the clinic to have the injection.
Tucatinib is a tablet. You have it twice a day, once in the morning and once in the evening. Do not chew or crush the tablets. You should take them at the same time each day and preferably with food. Your doctor will tell you how many tablets to take.
You have 24 weeks of palbociclib. You continue with letrozole, trastuzumab and tucatinib until you have surgery.
Please note while having treatment you must not eat grapefruit or drink grapefruit juice.
Drug diary
You have a diary to write down when you took your tablets and how many you took. You must bring this diary with you each time you have an appointment at the hospital.
Samples for research
The team take blood samples at the start and during the study. Where possible, they take them when you have blood taken as part of your routine care. Your doctor can tell you when and how often they take the blood samples.
The team ask for the tissue sample () that was taken when you were diagnosed. You have an ultrasound guided biopsy taken during:
- the 2nd week of treatment
- the 23rd week of treatment
They will also ask for some of the biopsy taken when you have your surgery. This biopsy is a part of the standard care.
They will use these samples to find out more about breast cancer and these treatments.
Hospital visits
You see the doctor for a and tests before taking part. The tests include:
- a breast scan such as an ultrasound, a mammogram or an MRI scan
- blood tests
- a heart scan - either an echo or
MUGA
You see the doctor regularly during treatment. This is to see how you are, for blood tests and to ask about side effects. The study team will tell you when and how often these appointments are.
You see the doctor at the start of your last week of taking the study treatment. This is to see how are and for some tests. The doctor will ask about any side effects.
Surgery
You have your surgery as planned after the end of the study treatment.
Follow up
You see the doctor 4 weeks after surgery. This is:
- to see how you are
- for blood tests
- to ask about side effects
Side effects
The study team monitor you during treatment and afterwards. Contact your advice line or tell your doctor or nurse if any side effects are bad or not getting better.
The most common side effects of palbociclib are:
- infections
- a drop in blood cells causing an increased risk of infection, bruising, bleeding, tiredness and breathlessness
- feeling tired (fatigue)
- sore, swollen mouth and lips
- feeling or being sick
- loss of hair
- diarrhoea
- loss of appetite
The most common side effects of letrozole are:
- hot flushes
- increased sweating
- stiff joints
- feeling tired (fatigue)
- high levels of cholesterol in the blood
- dryness of the vagina
- reduced interest in sex
The most common side effects of trastuzumab are:
- infection or a cold
- a drop in blood cells causing an increase in the risk of infection, bruising, bleeding, tiredness and breathlessness
- weight loss
- changes to taste
- difficulty sleeping (insomnia)
- shaking (tremor), dizziness, headaches
- nerve changes causing numbness and tingling (pins and needles)
- eye problems such as red, swollen eyes (conjunctivitis) and teary eyes
- changes to blood pressure
- changes to how regular the heart beats
- hot flushes
- shortness of breath and a cough
- runny nose and nosebleeds
- diarrhoea or constipation
- feeling or being sick
- swelling of the lips and face
- sore mouth
- skin rash and changes to the nails
- loss of hair
- swelling and blistering of the hands and feet (hand-foot syndrome)
- stiff joints, stiff and sore muscles
- tummy (abdominal) pain
- feeling tired and weak (fatigue)
- chest pain
- flu-like symptoms
- general pain
- high temperature (fever)
- sore, swollen hands and feet
The most common side effects of tucatinib are:
- feeling or being sick
- indigestion
- a drop in blood cells causing an increased risk of infection, bruising, bleeding, tiredness and breathlessness
- diarrhoea or constipation
- feeling tired (fatigue)
- dry mouth
- muscle pain, tummy (abdominal) pain, pain in the hands and feet
- headaches
- dry skin or skin rash
- swelling of the hands and legs
- changes to how your liver and kidneys work
- loss of appetite and changes to taste
- nosebleeds
We have more information about:
Your doctor will tell you about the possible side effects of the treatments and answer any questions you have before you agree to take part in the study.
Location
Recruitment start:
Recruitment end:
How to join a clinical trial
Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.
Chief Investigator
Professor Carlo Palmieri
Supported by
Pfizer
Seagen
University of Liverpool
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040