NCT04920708

Fulvestrant, Ipatasertib and CDK4/6 Inhibition in Metastatic ER+/HER2- Breast Cancer Patients Without ctDNA Suppression

Randomised Open-label Phase II Study of Induction Standard of Care Fulvestrant and CDK4/6 Inhibition With the Addition of Ipatasertib in Metastatic ER+/HER2- Breast Cancer Patients Without ctDNA Suppression

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 57 (actual)
• Sponsor: Royal Marsden NHS Foundation Trust · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Analysis of circulating tumour DNA (ctDNA) found in a patient's peripheral blood can identify cancer progression and predict a patient's response to therapy. By using ctDNA analysis and imaging techniques, the FAIM trial aims to determine whether the addition of the experimental drug ipatasertib to a standard combination of the hormone treatment fulvestrant and the targeted agent palbociclib increases progression free survival (PFS) for patients with hormone-receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer.

Detailed description

Circulating tumour DNA (ctDNA) can be found in the peripheral blood of patients with cancer. ctDNA analysis provides a readily available, serial source of tumour DNA which can be used to monitor disease and predict a patients response to therapy. Relative changes in ctDNA after 15 days of treatment with palbociclib and fulvestrant has been found to strongly predict progression free survival (PFS) in hormone-receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer patients: patients without ctDNA suppression after 2 weeks of treatment had a significantly shorter PFS compared to those with ctDNA suppression, identifying a group of patients who require additional therapy to prevent early progression. The FAIM trial is a randomised, open-label study which will aim to determine whether the addition of ipatasertib to standard of care CDK4/6 inhibitors + fulvestrant increases PFS in patients who lack ctDNA suppression after 15 days of treatment. Patients starting standard of care CDK4/6 inhibitors + fulvestrant will have a ctDNA assessment on cycle 1 day 1 (C1D1) and cycle 1 day 15 (C1D15). Those with high ctDNA levels at C1D15 will be randomised on a 1:1 basis to either standard of care (CDK4/6 inhibitors + fulvestrant) or standard of care plus the experimental drug ipatasertib (CDK4/6 inhibitor + fulvestrant + ipatasertib). Patients with ctDNA suppression at C1D15 will continue standard of care (fulvestrant+CDK4/6 inhibitor); the first 100 patients of this group will be followed for PFS and ctDNA collection. Patients without detectable ctDNA on C1D1 will be followed and treated according standard of care; the first 50 patients of this group will be followed for PFS, overall survival (OS), time to next treatment, and time to chemotherapy. Progression free survival will be monitored using RECIST 1.1.

Conditions

• Metastatic Breast Cancer
• ER+ Breast Cancer
• Advanced Breast Cancer

Interventions

Type	Name	Description
DRUG	Ipatasertib 300mg	Ipatasertib 300mg once daily. Oral administration. Treatment is continuous daily for 21 days, followed by 7 days off, to complete a 28 day cycle.
DRUG	Fulvestrant 500g	Fulvestrant 500mg administered intramuscularly in the buttocks slowly (1-2 minutes per injection) as two 5-mL injections (one in each buttock). Administered days 1 and 15 of Cycle 1. For subsequent cycles, patients will receive fulvestrant as described above in the clinic on Day 1 of each cycle or approximately every 4 weeks.
DRUG	Palbociclib 75mg-125mg	Palboclicib 75mg-125mg once daily, dependent on toxicities. Oral administration. Treatment is continuous daily for 21 days, followed by 7 days off, to complete a 28 day cycle.
DRUG	CDK4/6 Inhibitor	CDK4/6 inhibitor. As per current standard of care regime for ER+/HER2- breast cancer.

Timeline

• Start date: 2022-12-28
• Primary completion: 2027-06-01
• Completion: 2027-06-01
• First posted: 2021-06-10
• Last updated: 2026-04-14

Locations

13 sites across 1 country: United Kingdom