Re-challenge Therapy With Chemotherapy and Panitumumab in Metastatic Colorectal Cancer Patients Treated With an Anti-EGFR Therapy in 1st Line Treatment: a Phase II Multicentre Study.
试验速览
- 阶段
- 2 期
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Overall response rate (ORR)
研究概览
简要总结
patients with metastatic colorectal cancer who were initially RAS wild and failed at least 2 lines of chemotherapy will be enrolled. Anti-EGFR must have been given in 1st line. Those who remain RAS-wild upon retesting will receive rechallenge with panitumumab and chemotherapy
详细描述
This is a single arm pilot multicenter prospective study. We will recruit KRAS/RAS wild metastatic colorectal cancer patients who received at least 2 lines of chemotherapy and the 1st line must include cetuximab/panitumumab combined with chemotherapy. We will repeat RAS testing after progression on the last line of therapy. RAS testing will be taken via liquid biopsy using ctDNA or tissue biopsy from either a new tumour lesion or a previously present lesion which shows evidence of disease progression by radiological imaging. Only RAS-wild patients upon re-testing will be enrolled and will receive re-challenge therapy with panitumumab combined with chemotherapy similar to that given at 1st line (5-fluorouracil/leucoverin combined with oxaliplatin or irinotecan). Those converted to RAS mutant will not be enrolled.
All patients will be treated until disease progression, unacceptable toxic effects or withdrawal of consent.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed metastatic adenocarcinoma of the colon or rectum with initially KRAS/RAS wild tumours.
- •Patients received at least 2 lines of chemotherapy including a fluoropyrimidine, irinotecan and oxaliplatin± bevacizumab.
- •First line chemotherapy regimen with a fluoropyrimidine and irinotecan or fluoropyrimidine and oxaliplatin in addition to an anti-EGFR agent (cetuximab/panitumumab).
- •No evidence of disease progression for at least 4 months from the start of 1st line therapy.
- •At least one measurable lesion ≥ 10 mm as assessed by CT-scan or MRI must be available and accessible for re-biopsy and RAS testing.
- •Repeated RAS testing before re-challenge therapy must be done.
- •Age ≥18 years.
- •ECOG Performance status (PS) 0-
- •The patient has adequate organ function, defined as : Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, hemoglobin ≥ 9 g/dl, and platelets ≥ 100 x 109/L. Total bilirubin ≤ 1.5 times upper limit of normal value (ULN), serum alkaline phosphatase level < 5 times ULN, Serum creatinine level <1.5 mg/dl.
- •For female patients of childbearing potential, negative pregnancy test within 7 days before starting the study treatment.
- •Subject must provide informed consent prior to initiation of any study specific activities/procedures
排除标准
- •Significant cardiovascular disease including unstable angina or myocardial infarction within 12 months before initiation of study treatment or a history of ventricular arrhythmia (treated or not).
- •History or evidence of central nervous system metastasis (CT-scan or MRI are not mandatory if no clinical symptoms).
- •Known allergy or hypersensitivity to panitumumab.
- •Patients with right-sided colon cancer originating from the ascending colon or hepatic flexure.
- •Patients with known MSI-high status.
- •Patients with known HER2-positive status.
- •Previous or concurrent malignancy except for basal or squamous cell skin cancer, in situ carcinoma of the cervix, low-risk prostate cancer according to d'Amico classification or other solid tumors treated curatively and without evidence of recurrence for at least 5 years prior to the study.
- •Active or uncontrolled clinically serious infection.
- •Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness.
- •Other serious and uncontrolled non-malignant disease.
- •Pregnancy.
- •Breast feeding.
- •Treatment with any other investigational medicinal product within 28 days prior to study entry.
- •Concomitant administration of live, attenuated virus vaccine such as yellow fever vaccine.
研究组 & 干预措施
Single Arm
Panitumumab with FOLFOX6/FOLFIRI
干预措施: Panitumumab (Drug)
结局指标
主要结局
Overall response rate (ORR)
时间窗: 3 years
defined as the proportion of patients with tumour response (complete response or partial response) by RECIST criteria 1.1.
次要结局
- Progression-free survival (PFS)(3 years)
- Disease control rate (DCR)(3 years)
- Overall survival (OS)(3 years)