Culmerciclib Plus Anlotinib and Endocrine Therapy for HR-Positive/HER2-Negative Metastatic Breast Cancer With Brain Metastases

Официальное название

Efficacy and Safety of Culmerciclib Plus Anlotinib and Endocrine Therapy for HR-Positive/HER2-Negative Metastatic Breast Cancer With Brain Metastases：a Multicenter, Single-arm, Phase Ⅱ Trial

Обзор

This study aims to evaluate the efficacy and safety of adding the anti-angiogenic agent anlotinib to the combination of the CDK2/4/6 inhibitor Culmerciclib and endocrine therapy in patients with HR+/HER2- breast cancer and brain metastases. Eligible patients present with newly diagnosed brain metastases or brain metastases that progressed following prior local therapy. It is hoped that this therapeutic combination can achieve disease control in these patients.

Вмешательства

• Препарат Culmerciclib
  180 mg orally once daily
• Препарат Anlotinib
  12 mg orally once daily on Days 1-14 of every 3-week cycle
• Препарат Endocrine Therapy
  administered per approved prescribing information

Первичные конечные точки

• CNS progression-free survival(CNS-PFS) [Срок оценки: From enrollment to the end of treatment at 8 months]

Вторичные конечные точки (5)

• progression-free survival (PFS) [Срок оценки: From enrollment to the end of treatment at 8 months]
• objective response rate (ORR) [Срок оценки: From enrollment to the end of treatment at 8 months]
• intracranial objective response rate（IC-ORR) [Срок оценки: From enrollment to the end of treatment at 8 months]
• Overall Survival (OS) [Срок оценки: From enrollment to the end of treatment at 18 months]
• Safety and Adverse Events [Срок оценки: From enrollment to the end of treatment at 9 months]

Критерии участия

Критерии включения

• Women aged ≥ 18 years
• ECOG PS of 0-1
• Life expectancy of at least 12 weeks
• histologically or cytologically documented HR+/HER2- breast cancer
• radiologically confirmed brain parenchymal metastases without the need for immediate local therapy
• measurable brain metastasis lesion according to RANO-BM criteria
• Must have active brain metastases, defined as newly diagnosed brain metastases or progressive brain metastases following prior local therapy
• Prior systemic therapy must meet all the following criteria：

• No more than 3 lines of prior systemic therapy for advanced disease
• No more than 1 line of chemotherapy or antibody-drug conjugate (ADC) administered in the advanced setting
• No prior CDK4/6 inhibitor therapy for advanced disease, or only 1 line of CDK4/6 inhibitor therapy with treatment duration > 6 months
• Adequate hematological, hepatic and renal function
• Women of child bearing potential must agree to use a contraceptive method during the treatment period and for at least 180 days after the last dose of experiment treatment
• Patients must be able to participate and comply with treatment and follow-up

Критерии исключения

• Patients with leptomeningeal metastases, brainstem metastases or skull metastases
• Prior receipt of anti-angiogenic agents or Culmerciclib
• Unresolved Grade ≥2 toxicities (per CTCAE Version 6.0) attributable to any prior therapy, except alopecia
• Patients with visceral crisis,defined as severe organ dysfunction assessed by symptoms, signs, laboratory examinations and rapid disease progression
• Inability to swallow capsules or tablets
• Any severe and/or uncontrolled medical disease
• Other malignancies diagnosed within 5 years, excluding cured non-melanoma skin cancer, cervical carcinoma in situ and papillary thyroid carcinoma
• Radiographic evidence of tumor invasion of major vessels, or high risk of tumor invasion into major vessels resulting in life-threatening hemorrhage as assessed by the investigator
• Patients with arterial or venous thromboembolic events within 6 months, such as cerebrovascular accident, deep vein thrombosis and pulmonary embolism
• Participation in other anti-tumor clinical trials within 4 weeks prior to enrollment
• Any other condition that the investigator considers inappropriate to participate in this trial

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 9 центров

• Sun Yat-sen University Cancer Center — Гуанчжоу
• The Fourth Hospital of Hebei Medical University — Shijiazhuang
• Anyang Tumor Hospital — Anyang
• Henan Cancer Hospital — Чжэнчжоу
• Nanjing Drum Tower Hospital — Нанкин
• Nanchang People's Hospital — Nanchang
• The Second Affiliated Hospital of Dalian Medical University — Dalian
• Sichuan Provincial People's Hospital — Чэнду
• … и ещё 1 центр

Идентификаторы

NCT: NCT07745257 · SL-B2026-363-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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