Evaluating the Efficacy and Safety of Fulvestrant Plus DNA Damage Repair Inhibitors After a CDK4/6 Inhibitor
- Registration Number
- NCT05536128
- Lead Sponsor
- Seoul National University Hospital
- Brief 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 64
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Olaparib,Fulvestrant Olaparib Olaparib tablets should be taken at the same time each day, approximately 12 hours apart with one glass of water. The tablets should be swallowed whole and not chewed, crushed, dissolved or divided. Olaparib tablets can be taken with or without food. Fulvestrant should be administered on days 1, 15, 29, and then once monthly at 500 mg per dose. Olaparib,Fulvestrant Fulvestrant Olaparib tablets should be taken at the same time each day, approximately 12 hours apart with one glass of water. The tablets should be swallowed whole and not chewed, crushed, dissolved or divided. Olaparib tablets can be taken with or without food. Fulvestrant should be administered on days 1, 15, 29, and then once monthly at 500 mg per dose.
- Primary Outcome Measures
Name Time Method 6-month progression-free survival (PFS) rate Duration of response is the time from response to progression or death from any cause whichever is earlier. PFS rate is the number (%) of patients who are alive without any evidence of disease progression at 6 months.
- Secondary Outcome Measures
Name Time Method Safety and toxicity according to CTCAE v5.0 Duration of response is the time from response to progression or death from any cause whichever is earlier. All safety analyses will be performed on the Safety Population. Safety and tolerability will be assessed in terms of AEs, deaths, laboratory data, vital signs and ECGs. These will be collected for all patients. Appropriate summaries of these data will be described.
Translational research using tumour and blood samples Duration of response is the time from response to progression or death from any cause whichever is earlier. Collected samples will be used for potential development of biomarkers for response/resistance and safety
Progression-free survival (PFS) Duration of response is the time from response to progression or death from any cause whichever is earlier. PFS is defined as the time from the initiation of the study treatment to disease progression or death from any cause whichever is earlier. Progression-free survival will be estimated using the Kaplan-Meier method with 95% CI(Confidence interval).
Objective response rate (ORR) Duration of response is the time from response to progression or death from any cause whichever is earlier. ORR is defined as the number (%) of patients with at least 1 visit response of CR(Complete Response) or PR (Partial Response) per RECIST 1.1. Data obtained up until progression, or last evaluable assessment in the absence of progression, will be included in the assessment of response rate.
Duration of response Duration of response is the time from response to progression or death from any cause whichever is earlier. Duration of response is the time from response to progression or death from any cause whichever is earlier.
Trial Locations
- Locations (1)
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of