Clinical trial NCT05563922: Organ Preservation Strategy of Total Neoadjuvant Chemoradiotherapy for Low Rectal Carcinoma
Official title: Organ Preservation Strategy of Total Neoadjuvant Chemoradiotherapy for Early Low Rectal Carcinoma: A Prospective, Exploratory Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Rectal Cancer
Keywords: early low rectal cancer;total neoadjuvant treatment;TEM
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
First posted: 2022-10-03
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All the patients will receive neoadjuvant chemoradiotherapy ( CapOx + radiotherapy) for 2 cycles, one week after chemoradiotherapy, the first evaluation including MRI, colonoscopy, digital rectal examination and serum CEA will be conducted. Patients without tumor progression will continue 4 cycles of chemotherapy （CapOx） until next imaging and serum assessment. After the second assessment, for patients with tumor regression and suitable for TEM will receive local resection otherwise TME. Following treatment strategy will be made base on the final pathology evaluation after surgery, patients with good pathological response (ypT 0-1 without neural vascular invasion) will enter into the follow-up period, otherwise TME will be operated.
Primary purpose: TREATMENT

Brief summary: This study aims to evaluate the efficacy and safety of an organ-sparing strategy after neoadjuvant chemoradiotherapy followed by transanal endoscopic microsurgery （TEM） or endoscopic local resection for early low rectal cancer（cT 1-3N0M0）.Besides, the clinical complete response rate and near-clinical complete response rate, organ preservation rate, local recurrence rate, distant metastasis rate and quality of life （QoL） will also be assessed.


Eligibility criteria: Inclusion Criteria:

* Age≥18 years
* cT1-3N0M0 assessed by CT, MRI and ultrasound colonoscopy
* Rectal adenocarcinoma confirmed by biopsy pathology and the lower edge of the lesion was within 5cm from the anal edge
* Patients who have a strong desire to preserve the anus and are willing to accept neoadjuvant treatment, meanwhile is suitable for the implementation of organ preservation strategy after discussion within the multidisciplinary team of the hospital
* No previous treatment (including endoscopic resection, transanal local resection, radiotherapy, chemotherapy, etc.) before enrollment
* No contraindications to chemoradiotherapy
* No other colorectal organic diseases
* Voluntarily sign the informed consent

Exclusion Criteria:

* Have received previous treatment (including endoscopic resection, transanal local resection, radiotherapy, chemotherapy, etc.) before enrollment
* Patients with concurrent colorectal organic diseases
* Patients with familial polyposis
* Patients with a previous history of colorectal surgery or pelvic radiotherapy that may affect the outcome of this treatment
* Pregnant or lactating women
* The patient or family members could not understand the conditions and objectives of this study
* With a history of uncontrolled epilepsy, central nervous system diseases, or mental disorders, their clinical severity may hinder the signing of an informed consent form or affect their compliance with oral medication
* It is difficult to achieve complete remission base on existing evidence , such as: maximum diameter of cT2/T3 tumor\>4cm; suspicious Lateral lymph nodes (maximum diameter) =5mm; baseline CEA≥100; biopsy pathology contains signet ring cell carcinoma mucinous adenocarcinoma; evaluation team determines whether circumferential constrictive tumor should be included or not when necessary Severe heart disease, such as symptomatic coronary heart disease, New York Cardiology Association (NYHA) grade II or above severe congestive heart failure, or severe arrhythmia requiring pharmacological intervention, or a history of myocardial infarction within the last 12 months
* Organ transplantation requires immunosuppressive therapy
* Serious uncontrolled recurrent infections, or other serious uncontrolled concomitant diseases
* The baseline blood routine and biochemical indexes of the subject do not meet the following criteria: hemoglobin ≥90g / L; absolute neutrophil count (ANC) ≥1.5\*10\^9 / L; platelet ≥100\*10\^9 / L; ALT and AST≤ 2.5 times normal upper limit; ALP ≤2.5 times normal upper limit; serum total bilirubin \<1.5 times normal upper limit; serum normal creatinine"\<1 time upper limit; and serum albumin ≥30g / L

Primary outcomes:
measure: Organ preservation rate at 3 years
timeFrame: 3 years
Secondary outcomes:
measure: Clinical complete response rate after neoadjuvant chemoradiotherapy
timeFrame: 18 weeks
measure: 3-year local recurrence rate
timeFrame: 3 years
measure: 3-year distant metastases rate
timeFrame: 3 years
measure: 3-year Disease-free survival（DFS）rates
timeFrame: 3 years
measure: 3-year overall survival（OS） rates
timeFrame: 3 years
measure: Quality of life (EORTC-QLQ-C 30, psychological status)
timeFrame: 20 weeks
measure: 5-year Disease-free survival（DFS）rates
timeFrame: 5 years
measure: 5-year overall survival（OS） rates
timeFrame: 5 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Zhongshan Hospital
state: Shanghai
Study officials:
affiliation: Shanghai Zhongshan Hospital
name: Jian Wang, M.D.
role: PRINCIPAL_INVESTIGATOR
References: