In short
There are currently 2 ongoing clinical trials investigating treatments for conditions related to PIK3CA-activated mutation. These trials are taking place in Belgium, Italy, the Netherlands, and Spain, focusing on innovative targeted therapies for PIK3CA-related overgrowth disorders and advanced breast cancer with PIK3CA mutations.
Clinical trial locations
- Belgium
- Italy
- Netherlands
- Spain
Study on Alpelisib and Fulvestrant for Advanced Breast Cancer in Patients with PIK3CA Mutation and Hormone-Receptor Positive, HER2 Negative Tumors
This clinical trial is focused on advanced breast cancer that is hormone-receptor positive and HER2 negative, with a PIK3CA mutation. The study investigates a combination treatment using fulvestrant and alpelisib in patients whose cancer has progressed after previous fulvestrant therapy.
Who can participate: The trial is open to adults aged 18 or older, both women and men, with confirmed advanced breast cancer that has spread or returned and cannot be cured with surgery or radiation. Women must be postmenopausal, have had their ovaries removed, or be receiving LHRH analogue medication. Men must also receive LHRH-analogue treatment. Participants must have breast cancer with more than 10% of cells showing estrogen receptor or progesterone receptor expression and must be HER2 negative. They must have previously been treated with fulvestrant and shown disease progression, and must have been treated with a CDK4/6 inhibitor in the advanced stage. A confirmed activating PIK3CA mutation must be present, preferably in a metastasis. Participants need evaluable disease that can be measured according to specific guidelines and must have an ECOG performance status of 0, 1, or 2, indicating reasonable ability to carry out daily activities. Adequate organ and bone marrow function is required.
Who cannot participate: Patients who have not previously been treated with a CDK4/6 inhibitor or who do not have a PIK3CA mutation in their tumor are excluded. The study is only for pre- or postmenopausal women and men with hormone-receptor positive, HER2 negative advanced breast cancer.
Main focus: The study will monitor progression-free survival, tracking the time from enrollment to disease progression or death. Researchers will evaluate the objective response rate, clinical benefit rate, and duration of response. Safety and tolerability of the treatment will be continuously assessed, with particular attention to managing alpelisib-induced hyperglycemia (elevated blood sugar levels). The trial will also assess quality of life and patient-reported outcomes to understand the treatment's impact on daily living. The study is estimated to conclude by March 2026.
Investigational drugs: Fulvestrant is administered as a monthly injection into the muscle and works by blocking the effects of estrogen in the body, helping to slow or stop the growth of hormone-dependent breast cancer cells. Alpelisib is taken orally as film-coated tablets in dosages of 150 mg, 200 mg, or combinations thereof. It specifically targets and inhibits the PI3K protein, which is involved in cancer cell growth and survival, particularly in tumors with PIK3CA mutations.
Summary
The two ongoing clinical trials for PIK3CA-activated mutation represent distinct approaches to treating different conditions caused by this genetic alteration. One trial focuses on pediatric and young patients with overgrowth disorders using the experimental drug RLY-2608, while the other addresses advanced breast cancer in adults using the combination of alpelisib and fulvestrant. Both trials are investigating targeted therapies that specifically inhibit proteins affected by PIK3CA mutations, representing a precision medicine approach to treatment.
Geographically, the trials span four European countries, with the overgrowth disorder trial taking place in Belgium, Italy, and Spain, while the breast cancer trial is being conducted in the Netherlands. Both studies emphasize safety monitoring and careful patient selection based on confirmed PIK3CA mutations, reflecting the importance of genetic testing in modern clinical trials. These trials may provide valuable insights into managing conditions driven by PIK3CA mutations and potentially lead to new treatment options for affected individuals.
