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

Rectal Cancer Clinical Trial

Official title:

A Prospective, Multicenter, Randomized Controlled Trial of Neoadjuvant Therapy for High-risk Locally Advanced Rectal Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04543695
• Other study ID #: NCC201809007
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 15, 2020
• Est. completion date: June 1, 2025

Study information

• Verified date: March 2024
• Source: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 255
• Est. completion date: June 1, 2025
• Est. primary completion date: July 12, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 ful?lled: 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 ? 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.

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

Combination Product:
• Concurrent Chemoradiotherapy
Radiotherapy: 50Gy in 25 fractions to the primary tumor and to mesorectal, presacral,and internal iliac lymph nodes. Concurrent chemotherapy: Capecitabine 1650 mg/m2/d

Drug:
• XELOX
Intravenous infusion of oxaliplatin (130 mg/m2 over 2 h) on day 1 and oral administration of capecitabine (1000 mg/m2 twice daily) from day 1 to day 14, is repeated every 3 weeks for 6 cycles. 6 courses,3 weeks per course
• mFOLFOX
Administration of l-LV (400 mg/m2) and oxaliplatin (85 mg/ m2) by intravenous infusion over 2 h, followed by rapid intravenous infusion (iv) of 5-FU (400 mg/m2) and then slow infusion (civ) of 5-FU (2400 mg/m2 over 46 h), is repeated every 2 weeks for 9 cycles.

Procedure:
• TME
Total mesorectal excision

Locations

Country	Name	City	State
China	Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College	Beijing

Sponsors (6)

Lead Sponsor	Collaborator
Cancer Institute and Hospital, Chinese Academy of Medical Sciences	Cancer Hospital of Guizhou Province, Jilin Provincial Tumor Hospital, Peking Union Medical College Hospital, Peking University Cancer Hospital & Institute, Xijing Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The rate of tumor down-staging	Tumor down-staging is considered as Stage yp0-II after surgery, and watch-and-wait strategy after complete clinical response (cCR) was allowed.	6-8 months
Secondary	Rate of compliance with TNT	Rate of compliance with TNT	6-8 months
Secondary	3y OS	3-year overall survival (3yOS)	3years
Secondary	3y DFS	3-year disease free survival (3yDFS)	3years
Secondary	3y DMFS	3-year distant metastatic free survival(3yDMFS)	3 years
Secondary	3y LRRFS	3-year locoregional recurrence-free survival(3yLRRFS)	3 years
Secondary	EORTC QLQ-C30	EORTC QLQ-C30 to assess the quality of life	3 years
Secondary	EORTC QLQ-CR29	EORTC QLQ-CR29 to assess the quality of life	3 years
Secondary	Wexner continence grading scale	Wexner continence grading scale	3 years
Secondary	CTCAE 4.0	Severe acute adverse reaction rate(=III degree)	6-8months
Secondary	Incidence of surgical complications	Incidence of surgical complications	6-8 months