Adjuvant Chemotherapy for Prevention of Recurrence in Patients With Detectable ctDNA After Surgery in High-Risk Rectal Cancer
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 103
- 试验地点
- 25
- 主要终点
- Disease-free survival, intention-to-treat
研究概览
简要总结
The goal of this clinical trial is to investigate whether adjuvant chemotherapy can prevent disease recurrence in patients with high-risk rectal cancer who have detectable ctDNA after surgery.
The main research question the REACT study aims to answer is:
- Does adjuvant chemotherapy improve disease-free survival in patients with high-risk rectal cancer with detectable ctDNA after surgery?
Interventions:
- Patients with detectable ctDNA after surgery and randomised to the experimental group will be offered adjuvant chemotherapy (4 cycles CAPOX/6 cycles FOLFOX) within 12 weeks after surgery.
详细描述
Rationale - Rectal cancer is a worldwide cause of cancer related mortality. The incidence of rectal cancer in the Netherlands is approximately 3500 patients per year. The introduction of combined neoadjuvant (chemo)radiotherapy and total mesorectal excision (TME) has significantly reduced the local recurrence rate, but distant recurrence rates remain around 30%. Recurrences are likely to derive from residual local disease or subclinical metastatic disease (minimal residual disease). These micro metastases are undetectable by the currently used imaging techniques but still present after surgery. Adjuvant chemotherapy might be beneficial for patients at high risk for recurrence. However, there are only a few randomised controlled trials on perioperative chemotherapy available. Studies on adjuvant chemotherapy in rectal cancer yielded conflicting results. As a consequence, treatment with adjuvant chemotherapy in patients with rectal cancer is not evidence based and therefore not standard of care in the Netherlands. Recent studies suggest that preoperative intensive chemotherapy with radiotherapy, compared to standard chemotherapy and radiotherapy, resulted in a prolonged disease-free survival and overall survival. However, this was at the cost of increased toxicity, and whether the observed improvement in overall survival can be attributed to the addition of neo-adjuvant intensive chemotherapy is under debate. Consequently, there is an urgent need for biomarkers to identify those patients at high risk to recur after standard treatment, to select the patients that might benefit the most from adjuvant chemotherapy.
Objective - To investigate disease-free survival in patients with high-risk rectal cancer by treating these patients with adjuvant chemotherapy in case of detectable ctDNA after surgery.
Main trial endpoints - The primary endpoint of the study will be disease-free survival in the intention-to-treat population, calculated from the date of surgery to the date of recurrence or death from any cause of the patient, whichever occurs first.
Secondary trial endpoints - Secondary outcomes will be disease-free survival, carried out as per protocol analysis to analyse pure treatment effect. In addition, overall survival will be calculated measured from the date of surgery to the date of death from any cause. Quality of life will be assessed in both groups by obtaining already completed questionnaires provided by the PLCRC cohort study to compare the effect of adjuvant chemotherapy on quality of life. The robustness of ctDNA as biomarker will be analysed by comparing the disease-free survival of patients with detectable ctDNA who are not treated adjuvant chemotherapy (control group) with patients with undetectable ctDNA. The clearance of ctDNA of the patients who received adjuvant chemotherapy in the experimental group will be compared with the patients in the control group. Lastly, the co-occurrence of ctDNA in peripheral blood at the timing of detection of recurrent disease on imaging will be studied.
Trial design - The proposed study is conducted within the prospective Dutch ColoRectal Cancer (PLCRC) cohort and follows the trial within cohort (TwiCs) design, i.e. a randomised controlled trial within a prospective cohort.
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
- 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
- •Detectable ctDNA in the postoperative blood sample
- •Age ≥ 18 years
- •WHO performance score 0-1
- •Informed consent for PLCRC with specific consent for additional blood withdrawals and offering of future experimental research
- •Informed consent for the REACT trial.
- •Histological confirmed rectal cancer; either treated with neoadjuvant (chemo)radiotherapy, and/or clinical/pathological T3/T4 and/or N+ in case no neoadjuvant therapy was administered.
- •Eligible to receive treatment with combination adjuvant chemotherapy (CAPOX/FOLFOX) according to the treating physician.
- •Mentally competent and able to read and understand Dutch language.
排除标准
- •Metastatic disease
- •Another malignancy in previous 5 years, with the exception of treated carcinoma in situ or skin cancer other than melanoma
- •Incomplete primary tumour resection (R1 or R2 resection)
- •Contra-indication for fluoropyrimidines or oxaliplatin
- •Neoadjuvant oxaliplatin based systemic treatment, e.g. treated with the RAPIDO regimen consisting of short course radiotherapy followed by 6 cycles of CAPOX or 9 cycles of FOLFOX prior to surgery
- •Patients with a clinical complete response, who will not undergo surgery.
- •Pregnant and lactating women
- •History of psychiatric disability judged by the investigator to be clinically significant, precluding informed consent or interfering with compliance of the intervention group
- •Serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator
- •Serious infections (uncontrolled or requiring treatment)
- •Current or recent (within 28 days prior to randomisation) treatment with another investigational drug or participation in another study interfering with the primary endpoint.
研究组 & 干预措施
Adjuvant chemotherapy
Intervention group ctDNA+
干预措施: Adjuvant chemotherapy (Drug)
Standard of Care
Control group ctDNA+
结局指标
主要结局
Disease-free survival, intention-to-treat
时间窗: Calculated from the date of surgery to the date of progression (recurrence) or death from any cause of the patient, whichever occurs first, assessed up to 2 years of follow-up
To investigate whether the disease-free survival in patients with rectal cancer who have detectable ctDNA after primary tumour resection, can be improved by administration of adjuvant chemotherapy.
次要结局
- Overall survival, intention-to-treat(From the date of surgery to the date of death from any cause of the patient, with a median follow-up of 5 years)
- Disease-free survival, per-protocol(Calculated from the date of surgery to the date of progression (recurrence) or death from any cause of the patient, assessed up to 2 years of follow-up)
- Overall survival, per-protocol(Calculated from the date of surgery to the date of death from any cause of the patient, with a median follow-up of 5 years)
- The effect of adjuvant chemotherapy on quality of life - EQ-5D-5L(Questionnaires are obtained within PLCRC at baseline, 3 months, 6 months, 1 year, 1.5 years, 2 years and yearly after, assessed up to 4 years of follow-up)
- The effect of adjuvant chemotherapy on quality of life - QLQ-C30(Questionnaires are obtained within PLCRC at baseline, 3 months, 6 months, 1 year, 1.5 years, 2 years and yearly after, assessed up to 4 years of follow-up)
- The effect of adjuvant chemotherapy on quality of life - QLQ-CR29(Questionnaires are obtained within PLCRC at baseline, 3 months, 6 months, 1 year, 1.5 years, 2 years and yearly after, assessed up to 4 years of follow-up)
- Comparing disease-free survival of patients with detectable ctDNA but without receiving adjuvant chemotherapy with patients with undetectable ctDNA(Calculated from the date of surgery to the date of progression (recurrence) or death from any cause of the patient, assessed up to 2 years of follow-up)
- Comparing overall survival of patients with detectable ctDNA but without receiving adjuvant chemotherapy with patients with undetectable ctDNA(Calculated from the date of surgery to the date of death from any cause of the patient, with a median follow-up of five years)
- To investigate the prognostic value of ctDNA clearance after adjuvant chemotherapy(Two 10 mL CellSave blood samples will be collected at least 14 days after completion of chemotherapy. ctDNA clearance (yes/no) will be analyzed for correlation with disease-free survival at 2 years and overall survival at 5 years.)
- To investigate the co-occurrence of ctDNA in peripheral blood at the timing of detection of recurrent disease on imaging.(Up to 2 years after rectal surgery, at the time recurrent disease is detected on imaging and prior to any additional treatments.)
研究者
Mirthe Ubink
MD
Erasmus Medical Center