Efficacy, Safety and Exploratory Clinical Study of Bevacizumab Combined With Oxaliplatin and TAS-102 in First-line Treatment of Advanced Colorectal Cancer

Обзор

This study is a single-arm, prospective, open-label observational clinical study to evaluate the efficacy and safety of Bevacizumab combined with Oxaliplatin and TAS-102 in patients with advanced unresectable rectal cancer.

Подробное описание

Eligible subjects received Bevacizumab in combination with Oxaliplatin and the TAS-102 investigational drug, and Bevacizumab and Oxaliplatin were administered intravenously on day 1 of each cycle. Medicine, every 14 days as a course of treatment, TAS-102 orally administered, 35mg/m2 (maximum single dose 80mg), bid, orally on the 1st to 5th days, 2 weeks as a course of treatment.

Patients were treated until objective disease progression, worsening symptoms, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. Clinicians will comprehensively evaluate according to clinical treatment guidelines and clinical practice treatment principles. For patients who still benefit after progression, the investigator can decide whether to continue the treatment with Bevacizumab combined with Oxaliplatin and TAS-102. Efficacy objectives were assessed after all subjects completed treatment/termination visits. Subjects were assessed for safety throughout the study period through laboratory tests and adverse event reporting.

Вмешательства

• Препарат Bevacizumab combined with Oxaliplatin and TAS-102
  Bevacizumab (Anda, Qilu Pharmaceutical): 5 mg/kg, repeated every 2 weeks, administered by intravenous drip (ivgtt). Oxaliplatin: 85 mg/m2, repeated every 2 weeks, by intravenous infusion (ivgtt). TAS-102: 35 mg/m2 (maximum single dose 80 mg), orally, twice a day, on days 1 to 5, repeated every 2 weeks. Continuous administration until disease progression, death, toxicity intolerance, withdrawal of informed consent, or other reasons specified in the protocol; for patients who still benefit after

Первичные конечные точки

• Progression Free Survival (PFS) [Срок оценки: Up to 24 months]

Вторичные конечные точки (4)

• Disease Control Rate (DCR) [Срок оценки: Up to 24 months]
• Objective response rate (ORR) [Срок оценки: Up to 24 months]
• Overall survival (OS) [Срок оценки: Up to 24 months]
• Drug-Related Safety Indicators [Срок оценки: Up to 36 months]

Критерии участия

Критерии включения

• age: ≥18 years and ≤75 years;
• ECOG score 0\~1 points;
• advanced colorectal cancer patients
• According to RECIST1.1 criteria, there is at least one measurable target lesion, and tumor imaging evaluation is performed within 28 days before the first dose;
• Expected survival time ≥ 12 weeks;
• Major organ function is normal, that is, the following criteria are met:

（1）Routine blood examination standards must meet: ANC ≥1.5×109/L; PLT≥90×109/L; Hb ≥90g/L (no blood transfusion within 14 days); (2) Biochemical tests should meet the following criteria: ALB≥30g/L; (no ALB transfusion within 14 days); TBIL≤Upper limit of normal (ULN); ALT and AST≤2.5 times upper limit of normal (ULN), if liver metastasis , then ALT and AST≤5ULN; alkaline phosphatase≤2.5 times the upper limit of normal (ULN); BUN and Cr≤1.5×ULN and creatinine clearance rate≥50mL/min (CockcroftGault formula); (3) Cardiac ultrasound and echocardiography: left ventricular ejection fraction (LVEF≥55%); (4) QT interval (QTcF) corrected by Fridericia method of 18-lead ECG in females <470 ms; 7. For premenopausal or surgically sterilized female patients: Consent to abstinence or use of effective contraception during treatment and for at least 7 months after the last dose of study treatment; 8. Voluntarily joined the study and signed the informed consent.

Критерии исключения

• Patients who have received first-line standard therapy;
• Previous antitumor therapy or radiation therapy for any malignant tumor;
• concurrently receiving anti-tumor therapy in other clinical trials, including endocrine therapy, bisphosphonate therapy, or immunotherapy;
• Has undergone major surgical procedures not related to colorectal cancer within 4 weeks prior to enrollment, or the patient has not fully recovered from such surgical procedures;
• Serious heart disease or discomfort, including but not limited to the following:

• Diagnosed history of heart failure or systolic dysfunction (LVEF < 50%)
• High-risk uncontrolled arrhythmias, such as atrial tachycardia, resting heart rate >100 bpm, significant ventricular arrhythmia (eg, ventricular tachycardia), or higher-grade AV block (ie, Mobitz II second-degree AV block or third-degree AV blocklag)
• Angina pectoris requiring antianginal drug treatment
• Clinically significant heart valve disease
• ECG showing transmural myocardial infarction
• Poorly controlled hypertension (systolic > 180 mmHg and/or diastolic > 100 mmHg)
• Inability to swallow, bowel obstruction, or other factors that interfere with drug taking and absorption;
• Known history of allergies to the drug components of this regimen; history of immunodeficiency, including positive HIV test, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation;
• Pregnant or lactating female patients, female patients of childbearing potential with a positive baseline pregnancy test, or patients of childbearing age who are unwilling to take effective contraceptive measures during the entire trial period and within 7 months after the last study drug;
• Serious comorbidities or other comorbidities that would interfere with planned treatment, or any other condition in which the patient is considered unsuitable for participation in this study by the investigator.

Dropout/Rejection Criteria:

• The efficacy and/or safety evaluation cannot be performed due to the medication not prescribed in this protocol;
• Participating in other anti-tumor treatments while participating in this study will be assessed by the investigator as affecting the efficacy evaluation.

Termination criteria:

• The subject withdraws informed consent and requests to withdraw;
• During the course of the study, the subject has a pregnancy event;
• Subjects who cannot tolerate toxicity;
• Disease progression;
• Other circumstances in which the investigator considers it necessary to withdraw from the 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

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT05364489 · BOT-CRC-1LT

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗