Ongoing Clinical Trials for PIK3CA-Activated Mutation
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 of RLY-2608 for Adults and Children with PIK3CA-Related Overgrowth and Malformations
This trial is investigating RLY-2608, an experimental medication designed to target the specific protein affected by PIK3CA mutations. The study aims to find the best dose of this capsule medication and evaluate its safety and effectiveness in managing symptoms associated with PIK3CA-related overgrowth and malformations.
Who can participate: The trial is open to children and young people aged 2 to 17 years with a clinical diagnosis of PIK3CA-Related Overgrowth Spectrum or malformations classified by ISSVA 2018 standards. Participants must have documented activating PIK3CA mutations in affected tissue or cell-free DNA from the lesion or blood. They need to provide archived tissue or fluid samples, or be willing to undergo a biopsy if medically safe. Participants must have a Lansky performance status of 50 or higher if under 16 years old, or a Karnofsky performance status of 50 or higher if 16 years or older, meaning they can perform everyday activities reasonably well.
Who cannot participate: The trial excludes patients with other serious health conditions that might interfere with the study, those who are pregnant or breastfeeding, and patients who have participated in another clinical trial within the last 30 days. Patients with known allergies to the study medication, those unable to follow study procedures, patients with certain types of cancer history unless in remission for a specified period, those with severe liver or kidney disease, uncontrolled high blood pressure, or a history of heart attack or stroke within the last 6 months are also excluded. Patients currently using certain medications that might interfere with the study drug cannot participate.
Main focus: The trial will explore how well RLY-2608 works in reducing the size of overgrowths or malformations by comparing it to a placebo. Researchers will monitor participants over time to observe changes in their condition and ensure their safety. The study includes initial assessment, medication administration, regular monitoring for side effects, and evaluation of changes in lesion volume.
Investigational drug: RLY-2608 is an oral medication that selectively inhibits the mutant form of the PI3Kα enzyme, which plays a role in abnormal cell growth. By targeting this specific protein, the medication may help reduce abnormal growth and improve symptoms in patients with PIK3CA-related conditions.
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.
