BCT 1901 (CAPTURE): Women or men with oestrogen receptor positive, HER2 negative advanced breast cancer and PIK3CA mutant circulating DNA will be randomised to evaluate treatment with alpelisib plus fulvestrant compared with capecitabine on progression free survival.

Abstract

This study aims to find out whether treatment with alpelisib plus fulvestrant increases progression-free survival compared to capecitabine in women and men with eostrogen receptor positive (ER+), HER2-negative advanced breast cancer who have a PIKC3A mutation identified in circulating tumour DNA (ctDNA).

Who is it for? This study may be suitable for you if you are 18 years or older, have advanced ER+, HER2-negative breast cancer, and have already had treatment with a CDK4/6 inhibitor and an aromatase inhibitor.

Potential participants will consent to a blood test to find out if the cancer has a PIK3CA mutation. This mutation occur in 35-40% of ER+ breast cancers and may make tumours more sensitive to treatments, such as alpelisib, that target the PI3K pathway (which is important for cell growth and survival).

The PIKC3A gene mutation can be detected through a blood test for circulating tumour DNA. As a cancer grows, cancer cells die and are replaced by new ones. The dead cells get broken down and their contents, including DNA, go into the bloodstream. These very small pieces of DNA are called circulating tumour DNA (ctDNA).

Trial Details If a PIK3CA mutation is identified, before being randomised, participants will have their health checked, medical history recorded, standard blood tests, and provide a tumour biopsy (either a new biopsy or provide material collected earlier).

Participants will be randomised 1:1 to either: Arm A: alpelisib plus fulvestrant (clinic visits every 28 days) Arm B: capecitabine (clinic visits every 21 days)

Participants on Arm A will take 1 alpelisib tablet per day with fulvestrant injected intramuscularly once every 28 days. Women who are pre- or perimenopausal will also have a goserelin implant inserted under their skin to stop their ovaries producing oestrogen.

Participants on Arm B will take 1 capecitabine tablet twice per day on Days 1 to 14 of a 21 day cycle.

All participants will be regularly monitored throughout treatment to evaluate their health. Tumours will be assessed by imaging (CT scan, Bone Scan, MRI or PET scan if clinically indicated) and as per RECIST 1.1 every 8 weeks during treatment. Treatment will continue until documented disease progression .

The following biological samples will be collected: * Tumour samples of archived tissue or a new biopsy at screening (before first dose of study treatment); * Blood samples for ctDNA testing at pre-screening (to confirm eligibility), Cycle 1 Day 1, Cycle 1 Day 15 (Arm A only), at every cycle during treatment and the End of Treatment Visit. In the event of DNA extraction failure, a replacement blood sample may be requested from the participant. * Tissue collection at disease progression is suggested (optional).

Participants will have their final visit 28 days after their last dose of study treatment.

It is hoped this research will provide a new treatment option for people with incurable breast cancer.