A Study of Total Neoadjuvant Therapy for High-risk Locally Advanced Rectal Cancer

Phase 2

Active, not recruiting

• Conditions: Rectal Cancer
• Interventions: Combination Product: Concurrent Chemoradiotherapy; Drug: XELOX; Drug: mFOLFOX; Procedure: TME

• Registration Number: NCT04543695
• Lead Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

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.

Study Timeline

• Study First Submitted: 2020-08-03
• Study Start: 2020-08-15
• Study First Submitted QC: 2020-09-09
• Study First Posted: 2020-09-10
• Primary Completion: 2022-07-12
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-25
• Last Update Posted: 2024-03-26
• Study Completion: 2025-06-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 255

Inclusion Criteria

Not provided

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
adjuvant chemotherapy group	Concurrent Chemoradiotherapy	concurrent chemoradiotherapy → TME → adjuvant chemotherapy (control group)
adjuvant chemotherapy group	XELOX	concurrent chemoradiotherapy → TME → adjuvant chemotherapy (control group)
adjuvant chemotherapy group	mFOLFOX	concurrent chemoradiotherapy → TME → adjuvant chemotherapy (control group)
adjuvant chemotherapy group	TME	concurrent chemoradiotherapy → TME → adjuvant chemotherapy (control group)
consolidation chemotherapy group (CNCT group)	Concurrent Chemoradiotherapy	concurrent chemoradiotherapy → consolidation chemotherapy → TME (CNCT group)
consolidation chemotherapy group (CNCT group)	XELOX	concurrent chemoradiotherapy → consolidation chemotherapy → TME (CNCT group)
consolidation chemotherapy group (CNCT group)	mFOLFOX	concurrent chemoradiotherapy → consolidation chemotherapy → TME (CNCT group)
consolidation chemotherapy group (CNCT group)	TME	concurrent chemoradiotherapy → consolidation chemotherapy → TME (CNCT group)
induction chemotherapy group (INCT group)	Concurrent Chemoradiotherapy	induction chemotherapy → concurrent chemoradiotherapy →TME ( INCT group).
induction chemotherapy group (INCT group)	XELOX	induction chemotherapy → concurrent chemoradiotherapy →TME ( INCT group).
induction chemotherapy group (INCT group)	mFOLFOX	induction chemotherapy → concurrent chemoradiotherapy →TME ( INCT group).
induction chemotherapy group (INCT group)	TME	induction chemotherapy → concurrent chemoradiotherapy →TME ( INCT group).

Primary Outcome Measures

Name	Time	Method
The rate of tumor down-staging	6-8 months	Tumor down-staging is considered as Stage yp0-II after surgery, and watch-and-wait strategy after complete clinical response (cCR) was allowed.

Secondary Outcome Measures

Name	Time	Method
Wexner continence grading scale	3 years	Wexner continence grading scale
3y LRRFS	3 years	3-year locoregional recurrence-free survival(3yLRRFS)
Rate of compliance with TNT	6-8 months	Rate of compliance with TNT
3y OS	3years	3-year overall survival (3yOS)
3y DFS	3years	3-year disease free survival (3yDFS)
3y DMFS	3 years	3-year distant metastatic free survival(3yDMFS)
EORTC QLQ-C30	3 years	EORTC QLQ-C30 to assess the quality of life
EORTC QLQ-CR29	3 years	EORTC QLQ-CR29 to assess the quality of life
CTCAE 4.0	6-8months	Severe acute adverse reaction rate（≥III degree）
Incidence of surgical complications	6-8 months	Incidence of surgical complications

Trial Locations

Locations (1)

Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; 🇨🇳 Beijing, China