Total Neoadjuvant Therapy for Rectal Cancer - a New Standard of Care?
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 400
- 试验地点
- 2
- 主要终点
- Postoperative complications
研究概览
简要总结
This study hypothesizes that approximately 50% of rectal cancer patients can preserve their rectum using a watch-and-wait strategy if they achieve a complete or near-complete clinical response to total neoadjuvant therapy (TNT). The objective is to determine whether the complications, quality of life, and survival rates of rectal cancer patients who have achieved a complete or near-complete clinical response to TNT, followed by a watch-and-wait approach, are comparable to those of patients who undergo surgery first. Additionally, the study aims to identify potential prognostic and predictive markers for rectal cancer and examine survival rates and factors influencing responses to chemoradiotherapy (CRT) or TNT.
The study is divided into two parts:
**Part One:** Participants with cT1N1, T2-T3 N0-1 rectal cancer, MRF-, and EMVI-, with surgery as one of the possible first-line treatment options, will be randomized into two groups. The experimental group will consist of participants receiving TNT, including CRT and consolidation chemotherapy (Ch). If these participants achieve a complete or near-complete clinical response, they will be observed using a watch-and-wait strategy, which is a non-operative approach. The control group will consist of participants who undergo surgical treatment initially.
**Part Two:** All participants with rectal cancer who have received CRT or TNT will be included. Additionally, participants diagnosed with rectal cancer who are scheduled for CRT or TNT but declined to participate in Part One or do not meet the inclusion criteria will also be included.
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
- Single (Participant)
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
- •Inclusion Criteria:
- •Over 18 years of age.
- •Participants who agreed to participate in the study signed an informed consent form.
- •The Eastern Cooperative Oncology Group (ECOG) score ranges from 0 to
- •Pathologically confirmed rectal adenocarcinoma.
- •Tumor up to 10 cm from the anus.
- •Magnetic resonance imaging (MRI) of the pelvis and computed tomography (CT) of the thorax and abdomen were performed to confirm the diagnosis.
- •cT1N1, T2-T3 N0 - 1, M0, MRF -, EMVI -.
- •Normal bone marrow function: blood leucocytes > 3.5 × 10⁹/l, neutrophils > 1.5 × 10⁹/l, platelets > 100 × 10⁹/l.
- •Normal renal function: creatinine within 1,5 × normal.
- •Normal liver function: blood bilirubin levels within 1,5 times normal, AST, ALT levels within 2,5 times the upper limit.
排除标准
- •Prior ST or Ch.
- •Participants who are not eligible for pelvic MRI.
- •Participants who have had a malignancy in the last 5 years, except for treatment for basal cell or squamous cell skin cancer or in situ cervical cancer.
- •ECOG status ≥
- •Distant metastases detected.
- •Participants with uncontrolled therapeutic or psychiatric conditions.
- •Infectious diseases requiring antibiotic treatment.
- •Inclusion Criteria:
- •Over 18 years of age.
- •Participants who agreed to participate in the study signed an informed consent form.
- •ECOG score between 0 and
- •Pathological confirmed rectal adenocarcinoma.
- •Stage I to III rectal cancer confirmed.
- •The tumor is localized up to 12 cm from the anus.
- •Participants who refused to participate in the first part of the study or did not meet the inclusion criteria for the first part.
- •Participants have received preoperative CRT or TNT or are in the planning stages of neoadjuvant treatment.
- •Exclusion Criteria:
- •New cancer two years after CRT.
- •Stage IV cancer before treatment.
- •Participants refusing to participate in the study or unable to sign the informed consent.
研究组 & 干预措施
Part one. The first group: an experimental group - TNT, organ preservation.
Participants in the experimental group will be treated with TNT - CRT plus consolidating Ch. Consolidation Ch lasts 12 weeks. The response to TNT will be assessed 4 to 5 weeks after the last cycle of Ch. Response assessment will be performed through digital examination, pelvic MRI, rectoscopy, and biopsy. Participants will be actively followed up and not treated after a complete or near-complete response. In case of non-response, participants will undergo surgery. If the participant is diagnosed with a near-complete clinical response and wishes to avoid surgery, the response is reassessed after 8 weeks. If there is no response, i.e., near-complete clinical response persists, the participant is offered surgery.
Participants in the experimental group do not receive adjuvant treatment after TNT and surgery.
干预措施: Radiation Therapy (Radiation)
Part one. The first group: an experimental group - TNT, organ preservation.
Participants in the experimental group will be treated with TNT - CRT plus consolidating Ch. Consolidation Ch lasts 12 weeks. The response to TNT will be assessed 4 to 5 weeks after the last cycle of Ch. Response assessment will be performed through digital examination, pelvic MRI, rectoscopy, and biopsy. Participants will be actively followed up and not treated after a complete or near-complete response. In case of non-response, participants will undergo surgery. If the participant is diagnosed with a near-complete clinical response and wishes to avoid surgery, the response is reassessed after 8 weeks. If there is no response, i.e., near-complete clinical response persists, the participant is offered surgery.
Participants in the experimental group do not receive adjuvant treatment after TNT and surgery.
干预措施: Chemoradiotherapy (Drug)
Part one. The first group: an experimental group - TNT, organ preservation.
Participants in the experimental group will be treated with TNT - CRT plus consolidating Ch. Consolidation Ch lasts 12 weeks. The response to TNT will be assessed 4 to 5 weeks after the last cycle of Ch. Response assessment will be performed through digital examination, pelvic MRI, rectoscopy, and biopsy. Participants will be actively followed up and not treated after a complete or near-complete response. In case of non-response, participants will undergo surgery. If the participant is diagnosed with a near-complete clinical response and wishes to avoid surgery, the response is reassessed after 8 weeks. If there is no response, i.e., near-complete clinical response persists, the participant is offered surgery.
Participants in the experimental group do not receive adjuvant treatment after TNT and surgery.
干预措施: Consolidation Chemotherapy (Drug)
Part one. The first group: an experimental group - TNT, organ preservation.
Participants in the experimental group will be treated with TNT - CRT plus consolidating Ch. Consolidation Ch lasts 12 weeks. The response to TNT will be assessed 4 to 5 weeks after the last cycle of Ch. Response assessment will be performed through digital examination, pelvic MRI, rectoscopy, and biopsy. Participants will be actively followed up and not treated after a complete or near-complete response. In case of non-response, participants will undergo surgery. If the participant is diagnosed with a near-complete clinical response and wishes to avoid surgery, the response is reassessed after 8 weeks. If there is no response, i.e., near-complete clinical response persists, the participant is offered surgery.
Participants in the experimental group do not receive adjuvant treatment after TNT and surgery.
干预措施: Surgery (Procedure)
Part two of the study
In the second part of the study, investigators will prospectively collect and analyze the personal medical records of participants who have already received treatment with CRT or TNT. No new diagnostic or therapeutic approaches will be implemented; routine clinical practices for long-term follow-up will continue. For participants who have not received specific treatment and do not meet the inclusion criteria for the first part of the study, as well as those who declined to participate in that part, investigators will follow the routine clinical practices for investigation, treatment, and follow-up as long as they meet the inclusion criteria for the second part of the study.
干预措施: Part two (Other)
结局指标
主要结局
Postoperative complications
时间窗: From the start of treatment until 3 months after surgery.
Assessed based on the Clavien Dindo classification.
TNT toxicity
时间窗: From the start of treatment until 3 months after TNT.
Local and systemic toxicity and (or) side effects will be recorded according to the general terminology criteria for adverse events version 5.0 (CTCAE v5.0).
Mortality rate
时间窗: From the start of treatment until 3 months after treatment.
Mortality after TNT or surgery.
Quality of life
时间窗: From the start of treatment until 3 years after treatment.
Quality of life Will be assessed using scoring manual of European Organisation For Research And Treatment Of Cancer of CR29 (Colorectal).
Low anterior resection syndrome rate.
时间窗: From the start of treatment until 3 years after treatment.
Assessed based on the LARS questionnaire
Fatigue
时间窗: From the start of treatment until 3 years after treatment
Fatigue will be assessed using scoring manual of the functional assessment of chronic illness therapy - fatigue (FACIT-F) questionnaire.
Complete clinical response rate
时间窗: 12 - 14 weeks after TNT
Criteria for Complete Clinical Response DRE: * Smooth, flat scar * No nodularity Endoscopy: * Pale smooth scar with or without telangiectasia * No ulceration, nodularity, or mucosal irregularities * No stricture MRT: * Fibrotic, linear scar with low signal intensity on T2-weighted images * No diffusion restriction * No suspicious lymph nodes All of the criteria must be satisfied to define a complete clinical response.
Near-complete clinical response rate
时间窗: 12 - 14 weeks after TNT
Near Complete Response DRE: \- Smooth induration or superficial minor mucosal irregularity Endoscopic: * Appearance with irregular small mucosal nodules, superficial ulceration, or mild persistent erythema MRI * Downstaging with or without residual fibrosis, small area of residual signal, and complete or partial regression of lymph nodes * Diffusion-weighted MRI with a small area of residual high signal intensity
次要结局
- Rectal preservation rate(3 years after TNT)
- Local regrowth rate(3 years after TNT)
- Overall survival(3 - 5 years.)
- Disease-free survival(3 - 5 years.)
- Local recurrence-free survival(3 - 5 years.)
- Distant metastasis-free survival(3 - 5 years.)
- Stoma free survival(3 - 5 years.)