A Phase II Clinical Study of the Efficacy and Safety of Culmerciclib Rechallenge in HR-positive, HER2-negative Breast Cancer Patients With Resistance to First-line Endocrine Therapy.

Официальное название

A Phase II Clinical Trial Evaluating the Efficacy and Safety of Culmerciclib Combined With Fulvestrant Compared to an Investigator-Selected CDK4/6 Inhibitor Combined With Fulvestrant in Patients With HR-Positive, HER2-Negative Breast Cancer Who Have Progressed After First-Line Endocrine Therapy

Обзор

To evaluate the efficacy and safety of Culmerciclib combined with fulvestrant compared with investigator-selected CDK4/6 inhibitors combined with fulvestrant in patients with HR-positive/HER2-negative breast cancer who have progressed after first-line endocrine therapy

Подробное описание

The study was a Randomized, open-label, multicenter design. Patients with dvanced HR+/HER2- breast cancer who had failed previous adjuvant treatment with CDK4/6 inhibitors in combination with endocrine therapy were treated with fulvestrant and Culmerciclib

Вмешательства

• Препарат CDK4/6 inhibitor
  investigator's choice of CDK4/6 inhibitor
• Препарат Culmerciclib
  CDK2/4/6 inhibitor
• Препарат Fulvestrant
  Fulvestrant

Первичные конечные точки

• PFS [Срок оценки: Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (approximately 1 years)]

Вторичные конечные точки (3)

• ORR [Срок оценки: max 6 months]
• DOR [Срок оценки: max 6 months]
• OS [Срок оценки: 5 years]

Критерии участия

Критерии включения

• 1\) Female, ≥18 years old; ≤ 75years old 2)ECOG score 0-2; 3) Predicted survival ≥3 months;Patients with locally advanced and/or metastatic breast cancer confirmed by histopathology with positive ER expression and negative HER2 expression; 5) Enrolled subjects must meet one of the following criteria regarding prior endocrine therapy: i) Received CDK4/6 inhibitor combined with endocrine therapy as adjuvant endocrine therapy, experienced recurrence or progression during or within 1 year after completion of adjuvant CDK4/6 inhibitor therapy, and did not receive subsequent endocrine therapy; ii) Recurrence or progression more than 1 year after completion of adjuvant endocrine monotherapy, followed by progression after receiving CDK4/6 inhibitor combined with endocrine therapy as first-line salvage endocrine therapy; iii) Newly diagnosed locally advanced or metastatic disease, with disease progression after receiving CDK4/6 inhibitor combined with endocrine therapy as first-line salvage endocrine therapy; 6)Participants with recurrent or metastatic disease may receive rescue chemotherapy, ADC, or rescue endocrine therapy not exceeding first-line treatment; 7) The time interval between non-endocrine therapy should be ≥2 weeks; 8) At least one extracranial measurable lesion as defined by RECIST V1.1 criteria; 9) The functions of vital organs meet the requirements; 10) Fertile subjects must have a negative pregnancy test 7 days before starting treatment and must use an appropriate contraceptive method during treatment and for three months after completion of treatment; 11) The patient is fully informed and voluntarily signs the informed consent.

Критерии исключения

• 1\) Previously diagnosed with HER2-positive breast cancer based on pathological testing; ; 2) Known allergy to the tested drug component; 3) inflammatory breast cancer at the time of screening; 4) pia meningeal metastasis confirmed by MRI or lumbar puncture; 5) Central nervous system metastasis confirmed by imaging; 6) To the best of the investigator's judgment, symptomatic visceral disease or any disease load or none is considered optimal Endocrine therapy options are not suitable for endocrine therapy; 7) Inability or unwillingness to swallow medication or receive intramuscular injections; 8) Gastrointestinal insufficiency or gastrointestinal disease (if not controlled) that may significantly affect study drug absorption Ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small intestine resection, etc.; 9) Patients with ascites, pleural effusion and pericardial effusion accompanied by clinical symptoms in the baseline period need drainage, or use it for the first time Patients with serous cavity drainage within 4 weeks before medication; 10) A history of immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency conditions, Or have a history of organ transplantation; 11) Other malignancies (cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, and Thyroid cancer is excluded); 12) had undergone major surgical procedures or significant trauma within 4 weeks prior to the start of treatment, or was expected to undergo major surgery Surgical treatment; 13) Concomitant diseases that, in the investigator's judgment, seriously endanger patient safety or interfere with patient completion of the study (e.g.

Severe hypertension, diabetes, thyroid disease, co-active hepatitis B/C, and other activities Sexual infection); 14) Inability to understand or follow research instructions and requirements; 15) The researcher decides that it is not suitable to participate in this study

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Fudan Cancer Center — Шанхай

Идентификаторы

NCT: NCT07666555 · RISE

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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