FULVESTRANT for HR-positive, HER2-negative metastatic breast cancer | Metastatic breast cancer

Inclusion criteria

• {"criterion_text":"- Female (both pre- and postmenopausal) patients with histologically confirmed diagnosis of adenocarcinoma of the breast with radiological evidence of metastatic disease\n- Estrogen Receptor (ER) and/or Progesteron Receptor (PgR) positive disease confirmed at immunohistochemistry (IHC), as either ER or PR expression ≥ 1%, at the time of metastatic diagnosis. Molecular assessment performed locally on either primary tumor tissue or a biopsy specimen from a metastatic site.\n- HER2 negative breast cancer by FISH or IHC (IHC 0, 1+, 2+ and/or FISH HER2: CEP17 ratio < 2.0) at the time of metastatic diagnosis.\n- Age at the time of signing the informed consent at least 18 years.\n- Disease progression after at least 6 months of first line endocrine therapy with CDK 4/6 inhibitors.\n- The patient must have evaluable disease according to RECIST 1.1 (either measurable or non-measurable)\n- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.\n- Adequate organ function (kidney, bone marrow and liver)\n- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 6 months after the last dose of study drugs.\n- Women of childbearing potential must have a negative highly sensitive serum or urine pregnancy test within 7 days prior to randomisation.\n- Female subjects who are breast feeding should discontinue nursing during protocol treatment\n- Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.\n- Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained, and documented according to the local regulatory requirements"}

Exclusion criteria

• {"criterion_text":"- Diagnosis of any secondary malignancy within the last 3 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix\n- Known hypersensitivity reaction to one of the compounds or substances used in this protocol\n- Pregnant women are excluded from the study\n- Male\n- Previous or synchronous diagnosis of HER2-positive or triple-negative breast cancer\n- Prior chemotherapy for metastatic disease.\n- Disease progression before 6 months of first line endocrine therapy with CDK 4/6 inhibitors\n- Major surgery < 28 days before randomisation\n- Any unresolved toxic effect of prior therapies or surgical procedures of Grade ≥ 2 according to Common Terminology Criteria of Adverse Events (CTCAE v5.0), with the exception of alopecia, peripheral neuropathy and other toxicities not considered a safety risk for the participant at investigator’s discretion\n- Uncontrolled significant active infections (≥ grade 3 according to CTCAE version 5), including active hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency Virus (HIV).\n- Uncontrolled intercurrent illness, including psychiatric conditions, that would, in the judgment of the investigator, limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent"}

Primary endpoints

• {"endpoint_text":"- Clinical Benefit Rate (CBR), defined as the proportion of patients achieving a Complete response (CR) or Partial response (PR) or Stable disease (SD) lasting at least 6 months, as assessed according to RECIST 1.1 criteria","definition_or_measurement_approach":"CBR defined as proportion achieving CR or PR or SD lasting ≥6 months; assessment performed according to RECIST 1.1 criteria."}

Secondary endpoints

• {"endpoint_text":"- Progression Free Survival (PFS), defined as time from second line treatment start until progression or death for any cause, whichever comes first","definition_or_measurement_approach":"Time from start of second-line treatment until documented progression or death from any cause."}
• {"endpoint_text":"- OS, defined as time from second line treatment start until death from any cause","definition_or_measurement_approach":"Time from start of second-line treatment until death from any cause."}
• {"endpoint_text":"- Prevalence of somatic alterations detected through plasma NGS in patients who are candidate to receiving second line therapy in HR+/HER2- MBC","definition_or_measurement_approach":"Prevalence measured by plasma NGS (next-generation sequencing) of somatic alterations in patients eligible for second-line therapy."}
• {"endpoint_text":"- Prognostic impact on PFS and OS of somatic alterations detected through plasma NGS in patients candidate to receiving second line therapy in HR+/HER2- MBC","definition_or_measurement_approach":"Association between presence of somatic alterations on plasma NGS and PFS/OS outcomes."}
• {"endpoint_text":"- Proportion of patients with a CTCs count ≥ 5/7.5 mL compared to those with a CTCs count <5/7.5 mL at baseline of second line therapy for HR+/HER2- MBC","definition_or_measurement_approach":"Baseline circulating tumor cell (CTC) counts measured with CellSearch; proportion with ≥5/7.5 mL versus <5/7.5 mL."}
• {"endpoint_text":"- Prognostic impact on PFS and OS of a CTCs count ≥ 5/7.5 mL with respect to CTCs count < 5/7.5 mL in patients candidate to receiving second line therapy in HR+/HER2- MBC","definition_or_measurement_approach":"Association between baseline CTC count categories (≥5/7.5 mL vs <5/7.5 mL) and PFS/OS."}

Italy

Earliest CTIS Part Ii Submission Date

24-02-2026

Latest Decision Or Authorization Date

31-03-2026

Processing Time Days

35

Number Of Sites

5

Number Of Participants

159

Primary sponsor

Full Name

Centro Di Riferimento Oncologico Di Aviano

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy