NCT05625087

Detection of Tumor DNA in the Blood of Patients Receiving Standard Therapy for Hormone Receptor-positive (HR+) Non-HER2 Expressing (HER2-) Metastatic Breast Cancer as a Tool to Select Those Who May Benefit From the Next Course of Fulvestrant in Combination With Alpelisib or Ribociclib

A ctDNA Screening Program in Patients With HR+, HER2- Metastatic Breast Cancer for Detection of High-risk Relapse Patients on Any CDK4/6 Inhibitor and a Randomised Phase II Study Comparing Alpelisib Combined With Fulvestrant to Ribociclib Combined With Fulvestrant, in Patients With Persistent Targetable PIK3CA Mutations

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 162 (estimated)
• Sponsor: UNICANCER · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

After an initial screening phase (SAFIR 03 - SCREENING) to identify patients with blood circulating mutated-PIK3CA tumours persistent, patients will be enrolled in the treatment phase of SAFIR 03 (SAFIR 03 - ARRIBA) that was designed as a randomised, open-label, multicentre, phase II study, for comparison of alpelisib to ribociclib in combination with fulvestrant (as the continuation of the CDK4/6 inhibitor-fulvestrant strategy) in terms of progression-free survival (PFS).

Detailed description

INDICATION The population eligible to the screening phase is composed of all women or men with HR+, HER2- metastatic breast cancer who are eligible for first-line treatment with a cyclin-dependent kinases (CDK) 4/6 inhibitor combined with fulvestrant (and a luteinizing hormone realeasing hormone (LH-RH) analogue in men and premenopausal women) in the context of the standard healthcare management. The screening will identify patients with high risk of relapse on any CDK4/6 inhibitor thanks to ctDNA kinetic between baseline and 4 weeks of treatment. The purpose is to early adapt the therapeutic intervention for ctDNA no drop patient to prevent from relapse. This study will propose an intervention for PIK3CA mutated patients with alpelisib vs. ribociclib. Other therapeutic approaches might be proposed to patients with wild type PIK3CA through other protocols. The randomised study phase will include patients with persistent mutations on exons 4, 9 or 20\* of PIK3CA ctDNA after 4 weeks of treatment with any CDK4/6 inhibitor-fulvestrant in first-line setting.

Conditions

• Breast Cancer Stage IV

Interventions

Type	Name	Description
DRUG	Alpelisib	Alpelisib 300 mg once daily + fulvestrant 500 mg every 28 days
DRUG	Ribociclib	Ribocilcib 600 mg once daily 3 weeks on/1 week off + fulvestrant 500 mg every 28 days

Timeline

• Start date: 2023-10-19
• Primary completion: 2028-07-01
• Completion: 2030-06-01
• First posted: 2022-11-22
• Last updated: 2025-08-20

Locations

44 sites across 1 country: France