Circulating Tumour DNA Based Decision for Adjuvant Treatment in Colon Cancer Stage II Evaluation (CIRCULATE) AIO-KRK-0217
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 4,812
- 试验地点
- 1
- 主要终点
- Disease free Survival (DFS)
研究概览
简要总结
The CIRCULATE study evaluates the adjuvant therapy in patients with colon cancer UICC stage II. The primary aim of the study is to compare the disease free survival in patients who are positive for postoperative circulating tumour DNA with vs. without capecitabine.
详细描述
CIRCULATE is an investigator-initiated, multicentre, prospective, randomised, controlled trial.
Screening phase:
Patients with colon cancer (or rectal cancer, if a radiation is not indicated i.e. due to the tumour localisation) are postoperatively screened for this trial.
For this purpose, they sign an informed consent for screening. The formalin fixed paraffin embedded (FFPE) tumour block is shipped to one of the central pathological laboratories and is analysed for microsatellite instability and by panel analysis for frequent mutations in the colorectal cancer. A plasma sample is sent in parallel to the central laboratory for ctDNA. The screening is preferably performed before the patient is discharged from the surgical department and at the latest 5 weeks after resection to allow sufficient time for the analysis.
The patient- specific tumour mutations known from the panel analysis are measure in the patients plasma by ultra deep sequencing. The results of the analysis - positive for circulating tumour DNA (ctDNApos) or negative for circulating tumour DNA (ctDNAneg) - is not communicated to the patient or the investigator.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Chemotherapy
Capecitabine mono or Capecitabine/Oxaliplatin as investigator choice:
Patients who are positive for postoperative ctDNA (ctDNApos) and not microsatellite instable are randomized (2:1) to adjuvant chemotherapy with capecitabine or to follow up.
Capecitabine 2 x 1250 mg/m^2, oral (d1-14), repeated at day 22 (- 2 ... + 6 days). Patients with a GFR between 30 and 50 ml/min start with capecitabine dose of 2 x 1000 mg/m^2. Treatment duration: 8 cycles (approx. 6 months)
Capecitabine, if combined with Oxaliplatin (investigator choice):
If the investigation decides to add oxaliplatin, the following schedule should be used:
[Oxaliplatin 130 mg/m^2 i.v. (2 hours on d1)] Capecitabine 2 x 1000 mg/m^2, oral (d1-14), repeated at day 22 (- 2 ... + 6 days) Treatment duration: 4 or 8 cycles (approx. 3 or 6 months)
干预措施: Capecitabine (Drug)
结局指标
主要结局
Disease free Survival (DFS)
时间窗: for the primary endpoint after 154 events (approx. 60 months after study start)
Disease free survival of ctDNA positive patients randomised to "chemotherapy" vs. "follow-up", measured from randomisation to any recurrence, metastasis, second colorectal or non colorectal cancer and death from any cause. The primary endpoint will be tested in all randomised ctDNA positive patients and be evaluated by a stratified log rank test. Interims analysis after 93 events (approx. 38 months after study start), final analysis for the primary endpoint after 154 events (approx. 60 months after study start).
次要结局
- Disease free and overall survival of ctDNApos vs. ctDNAneg patients randomized to "follow-up"(3 years and 5 years)
- Overall survival in ctDNApos patients with adjuvant therapy vs follow-up(5 years)
- Disease free survival in ctDNAneg patients randomised to follow up(3 years)
- Overall survival in ctDNAneg patients randomised to "follow up"(5 years)
- Site of metastases(5 years)
- Frequency of adverse events from start of chemotherapy until 30 days after chemotherapy(5 years)