Clinical trial NCT04543695: A Study of Total Neoadjuvant Therapy for High-risk Locally Advanced Rectal Cancer
Official title: A Prospective, Multicenter, Randomized Controlled Trial of Neoadjuvant Therapy for High-risk Locally Advanced Rectal Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Rectal Cancer
Keywords: Rectal Cancer
Radiotherapy
High Risk
Total Neoadjuvant Therapy
Lead sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Sponsor class: OTHER
Collaborators: name: Peking University Cancer Hospital & Institute
name: Peking Union Medical College Hospital
name: Jilin Provincial Tumor Hospital
name: Cancer Hospital of Guizhou Province
name: Xijing Hospital
First posted: 2020-09-10
Enrollment: 255
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A Phase II Study of Total Neoadjuvant Therapy for High-risk Locally Advanced Rectal Cancer

Detailed description: Recommended treatment of patients with locally advanced rectal cancer (LARC) includes preoperative chemoradiation (CRT), total mesorectal excision (TME) and postoperative adjuvant chemotherapy (ACT). However, treatments fail to show an improved therapeutic effect on high-risk patients now. Total neoadjuvant therapy (TNT) is a new try for rectal cancer treatment,and this trial aims to identify and select the more promising TNT sequence.

This trail is a multicenter, randomized, phase II trial . Eligible patients age from 18 to 75 years with histologically confirmed rectal adenocarcinoma. MRI is mandatory, and patients of stage II or III rectal cancer are eligible if any of the following criteria are fulﬁlled: Categories T4,Categories N2, MRF involvement, EMVI positive, and lateral lymph node involvement. Patients are randomly assigned to 3 groups, group 1: concurrent chemoradiotherapy → TME → adjuvant chemotherapy (control group);or group 2: concurrent chemoradiotherapy → consolidation chemotherapy → TME (CNCT group);Or group 3: induction chemotherapy → concurrent chemoradiotherapy →TME ( INCT group).The primary end point is the rate of tumor down-staging, which is deﬁned as stage yp0-II after surgery,and watch-and-wait strategy after complete clinical response (cCR) was allowed. Secondary end points include acute toxicity, compliance with TNT, surgical complications, 3-year overall survival (3yOS),3-year disease free survival (3yDFS),3-year distant metastatic free survival(3yDMFS),3-year locoregional recurrence-free survival(3yLRRFS) and quality of life.

Eligibility criteria: Inclusion criteria:

1. 18-75 years old, regardless of gender
2. Histologically confirmed rectal adenocarcinoma;
3. Up to 12 cm above the anal verge on the basis of rigid rectoscopy.
4. MRI of the rectum is acceptable;
5. Patients in stage II or III rectal cancer are eligible if any of the following criteria are fulﬁlled: Categories T4,Categories N2, MRF involvement, EMVI positive, and lateral lymph node involvement.
6. ECOG score 0-1 or KPS score ≥80.

Exclusion Criteria:

1. History of malignant tumor in other parts;
2. Cannot complete MRI; Allergic to 5-fu drugs; Allergic to platinum drugs;
3. During thrombolytic and anticoagulant therapy, the patient has bleeding diathesis or coagulation dysfunction; Or aneurysm, stroke, transient ischemic attack, arteriovenous malformation in the past year;
4. History of kidney, urine test found proteinuria or clinical renal function was significantly abnormal;
5. History of digestive tract fistula, perforation or severe ulcer;
6. Active infection is present; Clinically obvious heart disease; New York heart association (NYHA) of Ⅱ level or congestive heart failure; Unstable symptomatic arrhythmia or peripheral vascular disease ≥ grade II; Myocardial infarction and cerebrovascular accident occurred within 6 months before enrollment.

Primary outcomes:
measure: The rate of tumor down-staging
timeFrame: 6-8 months
Secondary outcomes:
measure: Rate of compliance with TNT
timeFrame: 6-8 months
measure: 3y OS
timeFrame: 3years
measure: 3y DFS
timeFrame: 3years
measure: 3y DMFS
timeFrame: 3 years
measure: 3y LRRFS
timeFrame: 3 years
measure: EORTC QLQ-C30
timeFrame: 3 years
measure: EORTC QLQ-CR29
timeFrame: 3 years
measure: Wexner continence grading scale
timeFrame: 3 years
measure: CTCAE 4.0
timeFrame: 6-8months
measure: Incidence of surgical complications
timeFrame: 6-8 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Study officials:
affiliation: Chinese Academy of Medical Sciences and Peking Union Medical College
name: Jing Jin, M.D.
role: STUDY_DIRECTOR
References: