Testing a new trio of drugs for advanced and metastatic breast cancer

Recruting new patients

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    What is this study about?

    This study, known as CAPItello-292, is testing a new combination of drugs to see if it can help treat advanced or spreading breast cancer. The drugs include one called capivasertib along with two others known as CDK4/6 inhibitors and another drug called fulvestrant. The study wants to see how well these work together and how safe they are. Firstly, they need to decide on the best dose of these drugs to use together. Then, the main part of the study will compare these drugs with the usual treatment – either of the CDK4/6 inhibitors with fulvestrant — to see which is better. Scientists will check the blood of the patients to see how much of the drugs are present. They also want to see how many people have side effects and how severe these are. Patients’ health will also be monitored, including heart tests, blood tests and checking vital signs. The ultimate goal is to see if this new treatment can slow down the growth of the cancer, or even shrink it. In simpler words, this is a study for people with a type of advanced breast cancer. It’s testing three drugs together — capivasertib, a CDK4/6 inhibitor, and fulvestrant. This study is made up of two parts. The first part is to decide on the right amount of these drugs to give at the same time. Then, they’ll test this against the usual treatment to see if it’s better. They’ll use blood tests to check how much of the drugs are in the body and will carefully watch for any side effects. They’ll also keep a close eye on people’s health overall. The main aim is to see if this new combination can stop the cancer from getting worse. The CAPItello-292 trial is aimed at patients with serious breast cancer that has started to spread. In this research, a new blend of three medicines, capivasertib, a CDK4/6 inhibitor, and fulvestrant, is being evaluated. First, researchers want to figure out the optimal dosing of these drugs when taken together. Then they’ll compare this combination to the standard treatment to see if it provides any additional benefits. They’ll take blood tests to track the amount of medication and continuously monitor for any potential side effects. The end goal is to see if this new drug mixture can slow or even decrease the growth of the cancer.

    Learn more about this Trial

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      Where does the clinical trial take place?

      Brasschaat , Belgium

      Bruxelles , Belgium

      Leuven , Belgium

      Aalborg , Denmark

      Aarhus N , Denmark

      Odense C , Denmark

      Bobigny , France

      Clermont Ferrand , France

      Limoges , France

      Lyon , France

      Plerin , France

      Rouen , France

      St Herblain , France

      Villejuif , France

      Augsburg , Germany

      Berlin , Germany

      Berlin , Germany

      Bottrop , Germany

      Dresden , Germany

      Erlangen , Germany

      Freiburg , Germany

      Georgsmarienhu00fctte , Germany

      Hamburg , Germany

      Hannover , Germany

      Heilbronn , Germany

      Kiel , Germany

      Leipzig , Germany

      Mannheim , Germany

      Mu00f6nchengladbach , Germany

      Mu00fcnster , Germany

      Regensburg , Germany

      Stade , Germany

      Trier , Germany

      Ulm , Germany

      Milan , Italy

      Misterbianco , Italy

      Bydgoszcz , Poland

      Kraku00f3w , Poland

      Lodz , Poland

      Warszawa , Poland

      Barcelona , Spain

      Granada , Spain

      Lu00e9rida , Spain

      Madrid , Spain

      Madrid , Spain

      Mu00e1laga , Spain

      Pamplona , Spain

      Santiago de Compostela , Spain

      Lund , Sweden

      Solna , Sweden

      Vu00e4xju00f6 , Sweden

      Derry , United Kingdom

      Guildford , United Kingdom

      London , United Kingdom

      Taunton , United Kingdom

      York , United Kingdom

      Study Steps

      How Complex Will My Study Be and What Phases Will I Go Through?

      In this clinical trial, the steps a patient needs to take related to the administration of the drugs are as follows:

      For Capivasertib:

      1. During Phase Ib: Capivasertib is administered orally (PO) twice a day (BD) for 4 days on and then 3 days off per week, for a total of 4 weeks, which constitutes one 28-day cycle. The dosage will either be 320 mg or 400 mg based on findings during this phase.
      2. During Phase III: The administration schedule of Capivasertib remains the same as in Phase Ib, PO BD for 4 days on followed by 3 days off per week. However, the dosage will be as confirmed in the Phase Ib portion for a 28-day cycle.

      For Fulvestrant:

      1. During both Phase Ib and Phase III: Fulvestrant is administered as a 500 mg dose (delivered in 2 injections of 250 mg each) on Day 1 of Weeks 1 and 3 of Cycle 1, then on Day 1 of Week 1 for each subsequent cycle.

      These are the outlined steps for drug administration according to the study protocol.

      Diseases Under Investigation

      What Conditions Qualify Me for This Study?

      To be eligible for the study, you need to have the following disease-related criteria:

      1. Adult females (pre-/peri-/ and post-menopausal), and adult males.
      2. Histologically confirmed HR+/ HER2- breast cancer determined from the most recent tumor sample (primary or metastatic) per the American Society of Clinical Oncology and College of American Pathologists guideline. To fulfill the requirement of HR+ disease, a breast cancer must express ER with or without co-expression of progesterone receptor.
      3. Eligible for fulvestrant therapy and at least one of the following: palbociclib, ribociclib, or abemaciclib, as per local investigator assessment. Previous tolerance to specific CDK4/6 inhibitors and dose levels required.

      Additionally, for phase III of the study, there is an added disease-related inclusion criterion:

      1. Previous treatment with an ET (tamoxifen, AI, or oral SERD) as a single agent or in combination, with radiological evidence of breast cancer recurrence or progression while on, or within 12 months of, completing a (neo)adjuvant ET regimen.

      Please note that these are only disease-related criteria; there are other inclusion and exclusion criteria related to overall health and previous treatments that may also apply.

      Terms and conditions

      What Requirements I Have to Meet To Join This Study?

      When Am I Eligible to Join the Study?

      Inclusion Criteria:

      1. Adult females (pre-/peri- and post-menopausal), and adult males: This study is open to both women at any stage of menopause and men.
      2. Histologically confirmed HR+/ HER2- breast cancer: The cancer must be tested in a lab for specific markers. HR+ refers to hormones (estrogen and/or progesterone) promoting the growth of cancer cells. HER2- indicates the cancer cells do not make an excess of a protein called HER2. Histology involves examining cells under a microscope to identify disease.
      3. Eligible for fulvestrant therapy and CDK4/6 inhibitors: Fulvestrant is a type of hormone therapy. CDK4/6 inhibitors, such as palbociclib, ribociclib, or abemaciclib, are drugs that interfere with the growth of cancer cells. You must be suitable for these treatments.
      4. Adequate organ and bone marrow functions: This means that your organs and bone marrow must be working well enough to handle the study treatment. Tests will be done to confirm this.
      5. Consent to provide a mandatory FFPE tumour sample: You must agree to give a formalin-fixed paraffin-embedded (FFPE) tissue sample of your tumor for research purposes. These are tissue samples that have been preserved and can be used for detailed laboratory analysis.

      What Reasons Could Exclude Me from the Study?

      Key Exclusion Criteria Explained:

      1. Another Primary Malignancy: If you have a history of another type of cancer other than the cancer being treated in this study, you may be excluded unless your previous cancer was treated with intent to cure and there is no active disease 2 years before starting the study medication, and the risk of it coming back is low.
      2. Recent Radiotherapy: If you have undergone radiotherapy within 2 weeks prior to starting the study treatment.
      3. Recent Major Surgery or Injury: If you had major surgery or significant traumatic injury within 4 weeks before receiving the first dose of the study treatment.
      4. Persistent Side Effects from Prior Cancer Treatment: If you have ongoing side effects (worse than Grade 1 according to CTCAE) from previous cancer treatment, except for hair loss. If you have persistent effects that won’t be made worse by the study treatment, like certain types of hearing loss or peripheral sensory neuropathy, you might be included after consulting the study doctor.
      5. Unstable Central Nervous System Disease: If you have spinal cord compression or cancer that has spread to the brain or the lining of the brain and spinal cord, unless these have been definitively treated and are stable without the use of steroids for at least 4 weeks before starting the study treatment.
      6. Heart Issues: This includes abnormal heart rhythms, prior heart surgery or conditions, uncontrolled blood pressure, or a heart ejection fraction (a measure of how well your heart pumps blood) that’s below the normal range or less than 50%.
      7. Abnormal Heart Rhythm or Atrial Fibrillation: If you have uncontrolled or severe abnormal heart rhythms, including atrial fibrillation.
      8. Uncontrolled Diabetes or High Blood Sugar: Diabetes that requires insulin treatment or a hemoglobin A1c (a measure of average blood sugar over the past 2-3 months) of 8.0% or higher.
      9. Prior Organ Transplant: If you have had a previous allogeneic bone marrow transplant or any solid organ transplant.
      10. Prior Treatment with Certain Anticancer Drugs: This only applies to Phase III of the study. If you were previously treated with inhibitors targeting specific pathways (AKT, PI3K, or mTOR) or with CDK4/6 inhibitors for metastatic disease. Prior treatment with CDK4/6 inhibitors is allowed if it was in the adjuvant setting and there has been a treatment-free interval of at least 12 months.
      11. Prior Chemotherapy for Metastatic Disease: Also only for Phase III, if you have had more than one line of chemotherapy for metastatic disease.

      *The medical terms explained:*

      • CTCAE (Common Terminology Criteria for Adverse Events): A standard classification and severity grading scale for side effects of medical treatment.
      • QT interval/QTcF: A measurement on an electrocardiogram (ECG) that represents the time it takes for the heart’s ventricles to depolarize and repolarize (contract and relax).
      • ECG (Electrocardiogram): A test that records the electrical activity of the heart.
      • Left bundle branch block/Third-degree heart block: Conditions where there’s a delay or obstruction along the pathway that electrical impulses travel to make the heart beat.
      • NHYA (New York Heart Association) grade: A classification system to describe the severity of heart failure symptoms.
      • Ejection fraction: The percentage of blood that is ejected from the ventricles with each heartbeat. A normal range is typically between 50-70%.
      • Leptomeningeal metastases: Cancer that has spread to the membranes surrounding the brain and spinal cord.
      • Hemoglobin A1c (HbA1c): A lab test that shows the average level of blood sugar (glucose) over the previous three months.
      • Allogeneic bone marrow transplant: A procedure to replace damaged or destroyed bone marrow with healthy bone marrow stem cells from a donor.
      • AKT, PI3K, mTOR inhibitors: Types of targeted therapy drugs that block specific pathways involved in cancer cell growth and survival.
      • CDK4/6 inhibitors: Drugs that inhibit certain enzymes (cyclin-dependent kinases 4 and 6) which are involved in the growth of cancer cells.

      Please let me know if you need further explanations for any medical terms or other aspects of the study.

      Investigational Medicinal Product

      What Products Are Being Used in This Study?

      The drugs (active substances) involved in the study are:

      1. Fulvestrant: this is an estrogen receptor antagonist with no known hormone agonist effects. It works by targeting the estrogen receptor for degradation and thus lowering the level of estrogen receptor expression.
      2. Palbociclib: this is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6. As certain types of cancer cells require CDK4/6 activation to proliferate, the inhibition of these molecules can help in controlling the growth of cancer cells.

      These drugs are often used in the treatment of certain types of breast cancer and are being studied for their effectiveness alone or in combination with other treatments.

      Have the Medicinal Substances Used in the Trial Been Previously Studied in Medicine?

      The active substances participating in the clinical trial known as NCT04862663 include:

      1. Capivasertib: This substance is being tested at a dosing schedule of either 320 mg or 400 mg orally twice daily for 4 days on followed by 3 days off per week over a 4-week cycle (28 days cycle). In the Phase III portion of the trial, the dose of Capivasertib is administered at the confirmed dose from the Phase Ib portion following the same schedule.
      2. Fulvestrant: It is administered as 500 mg via two injections of 250 mg each on day 1 of weeks 1 and 3 of cycle 1, and then on day 1, week 1 of each cycle thereafter.
      3. Palbociclib: In Phase Ib, the dose for Palbociclib ranges from 100 mg to 125 mg once daily for 21 consecutive days followed by 7 days off to comprise a complete cycle of 28 days. In Phase III, it is administered at a dose of 125 mg once daily for 21 days of a 28-day cycle.
      4. Ribociclib: This drug is dosed at 200 mg to 600 mg once daily for 21 consecutive days followed by 7 days off to complete a 28-day cycle for Phase Ib. In Phase III, the dose confirmed in the Phase Ib portion is administered over the same schedule.

      These substances are known to medicine and are documented in the medical literature, as they are being used in various phases of this clinical trial to evaluate their efficacy and safety profiles. Fulvestrant, Palbociclib, and Ribociclib are already approved for clinical use in certain conditions, and Capivasertib is being investigated for its therapeutic potential.

      Study ID


      Recruitment status

      Recruting new patients

      Start of the trial

      3 years ago

      Study phase