Phase II Study of Irinotecan Liposomes in First-line Treatment of Metastatic Colorectal Cancer

Официальное название

Phase II Study of Irinotecan Liposomes Combined With 5-FU/LV+ Bevacizumab in First-line Treatment of Metastatic Colorectal Cancer

Обзор

To evaluate the objective response rate, disease control rate, progression-free survival, overall survival, surgical conversion rate and safety of irinotecan liposome combined with 5-FU/LV+ bevacizumab regimen in first-line treatment of advanced metastatic colorectal cancer patients.

Подробное описание

This is a Phase II clinical study to evaluate the efficacy and safety of the combination regimen of irinotecan liposome injection in the first-line treatment of metastatic colorectal cancer. Patients will receive liposomal injections of irinotecan 70mg/m\^2 d1, bevacizumab 5mg/kg d1, LV 400mg/m\^2 d1, 5-FU 400mg/m\^2, then 2400mg/m\^2, continuous intravenous infusion for 46-48h, d1-2. 86 eligible patients will be enrolled.

Вмешательства

• Препарат Irinotecan Liposome
  70 mg/m\^2 , d1, 14 days per cycle, 8 cycles.
• Препарат 5-FU
  5-FU 400mg/m\^2, then 2400mg/m\^2, continuous intravenous infusion for 46-48h, d1-2, 14 days per cycle, 8 cycles.
• Препарат LV
  400mg/m\^2, d1, 14 days per cycle, 8 cycles.
• Препарат Bevacizumab
  5mg/kg, d1, 14 days per cycle, 8 cycles.

Первичные конечные точки

• Objective response rate [Срок оценки: From initial medication to the date of first documented progression or end of medication or completed 8 cycles treatment, whichever came first . Assessed up to 4 months]

Вторичные конечные точки (6)

• Disease control rate [Срок оценки: From initial medication to the date of first documented progression or end of medication or completed 8 cycles treatment, whichever came first. Assessed up to 4 months]
• Progression free survival [Срок оценки: From initial medication to the date of first documented progression or end of medication, whichever came first. Assessed up to 30 months.]
• Overall survival [Срок оценки: From initial medication to the date of death from any cause. Assessed up to 30 months.]
• Percentage of patients undergoing surgery. [Срок оценки: From the first dose to completed 8 cycles treatment. Assessed up to 5 months.]
• R0 resection [Срок оценки: From the first dose to the surgery. Assessed up to 6 months.]
• Incidence of adverse events and severity of adverse events as assessed by CTCAE 5.0 [Срок оценки: From the first dose to completed 8 cycles treatment. Assessed up to 5 months.]

Критерии участия

Критерии включения

• 18\~85 years old.
• Histopathologically confirmed patient with an inoperable metastatic colorectal adenocarcinoma.
• RAS/BRAF v600e mutant or right half colon cancer is known.
• pMMR/MSS is known.
• The unresectable stage of metastatic disease has not received any systemic antitumor therapy.
• For subjects previously receiving neoadjuvant or adjuvant therapy, the date of first discovery of disease progression must be at least 6 months removed from the date of last administration of neoadjuvant or adjuvant therapy.
• ECOG 0\~1, patients ≥75 years old need an ECOG score of 0
• The presence of at least 1 measurable lesion that can be evaluated according to the RECIST v1.1 criteria.
• Normal bone marrow and organ function: ① Neutrophils (ANC) ≥1.5×10\^9/L, platelets (PLT) ≥100×10\^9/L, hemoglobin (Hb) ≥80g/L, albumin (ALB) ≥30 g/L, white blood cells (WBC) ≥3.0×10\^9/L, and no bleeding tendency; ② AST, ALT and alkaline phosphatase (ALP) were all ≤2.5× upper limit of normal range (ULN), and ≤5×ULN when liver metastases occurred; The total bilirubin level doesn't exceed the upper limit of the agency's normal range; Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance ≥40 ml/min (calculated according to Cockroft-Gault)
• Understand the situation of this study, patients and/or legal representatives voluntarily agree to participate in this study and sign informed consent form.

Критерии исключения

• Known or suspected central nervous system metastasis.
• Received irinotecan/irinotecan liposomes/bevacizumab before enrollment.
• Had undergone surgery and other oncologic treatments within the first 4 weeks of enrollment.
• Previous treatment-related toxicity didn't return to NCI-CTCAE v5.0 I or below(except hair loss and peripheral neuropathy).
• The use of CYP3A, CYP2C8, and UGT1A1 inhibitors or inducers couldn't be discontinued or were not discontinued within 2 weeks prior to enrollment.
• Severe gastrointestinal dysfunction, gastrointestinal perforation, intraperitoneal abscess, and fistula.
• Intestinal obstruction, signs and symptoms of intestinal obstruction, or the stent has been previously implanted and the stent has not been removed before the screening period.
• Interstitial lung disease.
• Tendency of arterial embolism and massive bleeding within 6 months before enrollment (except surgical bleeding).
• Patients with fluid accumulation that couldn't reach a stable state but small amount of ascites on imaging without clinical symptoms could be enrolled.
• Any serious or uncontrolled systemic disease, including uncontrolled high blood pressure, heart disease, active bleeding, active viral infection, etc.
• Have had other malignancies within the past 5 years or currently, except cured cervical carcinoma in situ, uterine carcinoma in situ, and non-melanoma skin cancer.
• Patients of childbearing age who refuse to take contraceptives, women who are pregnant or breastfeeding.
• The researchers didn't consider it appropriate 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

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• West China Hospital，Sichuan University — Sichuan

Идентификаторы

NCT: NCT06341296 · CSPC-DEY-CRC-K07

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗