NCT05536128

Evaluating the Efficacy and Safety of Fulvestrant Plus DNA Damage Repair Inhibitors After a CDK4/6 Inhibitor

A Phase II Open Label, Umbrella Study Evaluating the Efficacy and Safety of Fulvestrant Plus DNA Damage Repair Inhibitors in Hormone Receptor-positive Advanced Breast Cancer After a CDK4/6 Inhibitor

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 64 (estimated)
• Sponsor: Seoul National University Hospital · Academic / Other
• Sex: All
• Age: 19 Years
• Healthy volunteers: Not accepted

Summary

Protocol Title: A Phase II open label, umbrella study evaluating the efficacy and safety of Fulvestrant plus DNA damage repair inhibitors in hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor

Detailed description

Nearly 70% of breast cancers (BCs) express estrogen receptor and rely on estrogen binding for growth and promotion of tumourigenesis. Endocrine therapy (ET), such as aromatase inhibitors, are the mainstay initial therapy for hormone receptor-positive (HR+), human epidermal growth factor receptor two-negative (HER2-) BC. Recently, the combination of ET and cyclin-dependent kinase (CDK) 4/6 inhibitors has shown significant and meaningful clinical benefit and has become the standard of care in this setting. So far, three CDK4/6 inhibitors have been approved by both FDA and EMA(European Medicines Agency): palbociclib (Ibrance, Pfizer, USA), ribociclib (vissali, Novartis, Switzerland) and abemaciclib (Verzenio, Lilly, USA). All of these drugs are approved and are widely used in 1st-line treatment for metastatic HR+/HER2- BC in Korea. CDK4/6 inhibitors have revolutionized the treatment landscape of HR+ HER2- BC but intrinsic or acquired resistance is inevitable. Fulvestrant, a selective estrogen receptor degrader (SERD), is one of preferred agents as the 2nd line treatment after failure of an aromatase inhibitor. More data regarding treatment options and sequences after failure of CDK4/6 inhibitors and endocrine treatments are needed. This is an umbrella study of treatments according to the germline or somatic genetic alterations in this patient population. The main focus would include, but not be limited to, DNA damage repair (DDR) inhibitors plus fulvestrant combinations.

Conditions

• Advanced Breast Cancer

Interventions

Type	Name	Description
DRUG	Olaparib	Olaparib tablet 300 mg taken orally twice daily Olaparib 500 mg on Days 1, 15, 29, and every 4 weeks thereafter The treatment will continue till disease progression or unacceptable toxicity or withdrawal of consent or another discontinuation criterion is met.
DRUG	Fulvestrant	Fulvestrant 500 mg on Days 1, 15, 29, and every 4 weeks thereafter

Timeline

• Start date: 2022-12-31
• Primary completion: 2025-12-31
• Completion: 2025-12-31
• First posted: 2022-09-10
• Last updated: 2025-04-17

Locations

1 site across 1 country: South Korea