Abemaciclib Combined With FOLFOX/FOLFIRI Regimen in Patients With Advanced Colorectal Liver Metastases Cancer

Официальное название

Abemaciclib Combined With FOLFOX/FOLFIRI Regimen in Patients With Advanced Colorectal Liver Metastases Cancer Who Failed Standard Two or Three-line Therapy

Обзор

This is a single-center, single-arm, open-label clinical study, to explore the efficacy and safety of abemaciclib combined with FOLFOX/FOLFIRI regimen in patients with advanced colorectal liver metastases cancer who failed standard two or three-line therapy.

Подробное описание

Colorectal Cancer (CRC) is the third most common malignant tumor worldwide, and its mortality rate ranks second globally. Approximately 70% of distant metastases of colorectal cancer occur in the liver, and about 50% of colorectal cancers develop liver metastases (CRLM), which is one of the main factors contributing to the poor prognosis of colorectal cancer. FOLFOX and FOLFIRI regimens are standard therapy for CRLM. Abemaciclib, a FDA approved drug targeting CDK4/6 in breast cancer, also shows anti-tumor activities in other types of solid tumors. In our preclinical experiments, our results also indicated that Abemaciclib conbined with FOLFOX or FOLFIRI regimen showed synergistic anti-tumor activity in CRC.

Вмешательства

• Препарат Abemaciclib
  Abemaciclib was administered orally at 100-200mg twice daily for each 28-day cycle.
• Препарат Oxaliplatin
  85mg/m², ivdrip, D1
• Препарат Calcium Folinate
  400mg/m², ivdrip, D1; or calcium levofolinate, 200 mg/m², ivdrip, D1
• Препарат 5-Fluorouracil
  400mg/m², iv, D1; and 2400mg/m², civ, 46-48h
• Препарат Irinotecan
  180mg/m², ivdrip, D1

Первичные конечные точки

• ORR [Срок оценки: 12 months]

Вторичные конечные точки (4)

• PFS [Срок оценки: 12 months]
• DCR [Срок оценки: 12 months]
• TTP [Срок оценки: 12 months]
• ADRs [Срок оценки: 12 months]

Критерии участия

Критерии включения

• Informed consent has been signed
• Histologically or cytologically confirmed unresectable advanced colorectal liver metastases cancer
• Age ≥ 18 years, ≤75 years
• ECOG PS：0-1
• Patients who failed standard two or three-line therapy
• Expected overall survival ≥3 months
• Patients must have at least one measurable liver metastases (RECIST 1.1)
• Patients who have previously failed standard treatment, or who cannot tolerate standard treatment
• Patients must have adequate organ and bone marrow function
• Women of childbearing age must have a negative pregnancy test within the first day of the study, and contraceptive methods should be taken during the study until 6 months after the last administration

Критерии исключения

• Patients had other malignant tumors in the past 5 years or at the same time (except for the cured skin basal cell carcinoma and cervical carcinoma in situ);
• Patients who have previously received CDK inhibitors treatment;
• Patients with obstruction, bleeding or perforation who require surgical or interventional treatment;
• Patients who are allergic or suspected to be allergic to the study drug, similar drugs or drug excipients;
• Patients currently have central nervous system (CNS) metastasis or previous brain metastasis and the symptom control time is less than 2 months;
• Clinical uncontrolled active infections, including human immunodeficiency virus (HIV) infection, active hepatitis B / C (HBV DNA Positive\[1×104 copies/mL or >2000 IU/ml\], HCV RNA positive\[>1×103 copies/mL\]);
• Clinically significant cardiovascular disease, including but not limited to acute myocardial infarction, severe/unstable angina pectoris or coronary artery bypass grafting within 6 months before enrollment; NYHA classification > 2 Grade; ventricular arrhythmia requiring medical therapy; ECG showing QTc interval > 450 ms (Male) or 470ms (Female);
• Abnormal coagulation function (INR>2.3 or APTT>1.5×ULN), with a bleeding tendency or currently undergoing thrombolytic or anticoagulant therapy;
• Hereditary or acquired tendency for bleeding and thrombosis, such as hemophilia, coagulation disorders, thrombocytopenia, hypersplenism;
• Within 3 months prior to entering the study, clinically bleeding symptoms or bleeding tendency, such as gastrointestinal bleeding without ligation or sclerotherapy injection, hemorrhagic gastric ulcer, positive Fecal Occult Blood Test (++ or above), or suffering from phlebitis;
• Arterial/venous thrombotic events that occurred within 6 months, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism;
• Long-term anticoagulation therapy with warfarin or heparin is required, or long-term antiplatelet therapy (aspirin ≥300 mg/ day or clopidogrel ≥75 mg/ day) is needed;
• Concurrent severe infection within 2 weeks before the first administration (e.g., requiring intravenous infusion of antibiotics, antifungal or antiviral drugs), or unexplained fever during screening/before the first administration (>38.5°C);
• A known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
• Participating in other clinical trials and received at least one treatment within 3 months before enrollment;
• A history of abuse or drug use of psychotropic substances;
• Patients with other serious physical or mental illnesses or abnormal laboratory tests that may increase the risk of participating in the study or interfere with the research results, as well as those deemed unsuitable for participation in this study by the researchers.

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 · 1 центр

• Shanghai Cancer Center — Шанхай

Идентификаторы

NCT: NCT07441369 · GWK-2026-002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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