- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04543695
A Study of Total Neoadjuvant Therapy for High-risk Locally Advanced Rectal Cancer
A Prospective, Multicenter, Randomized Controlled Trial of Neoadjuvant Therapy for High-risk Locally Advanced Rectal Cancer
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Beijing, China, 100021
- Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion criteria:
- 18-75 years old, regardless of gender
- Histologically confirmed rectal adenocarcinoma;
- Up to 12 cm above the anal verge on the basis of rigid rectoscopy.
- MRI of the rectum is acceptable;
- 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.
- ECOG score 0-1 or KPS score ≥80.
Exclusion Criteria:
- History of malignant tumor in other parts;
- Cannot complete MRI; Allergic to 5-fu drugs; Allergic to platinum drugs;
- 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;
- History of kidney, urine test found proteinuria or clinical renal function was significantly abnormal;
- History of digestive tract fistula, perforation or severe ulcer;
- 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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: adjuvant chemotherapy group
concurrent chemoradiotherapy → TME → adjuvant chemotherapy (control group)
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Total mesorectal excision
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 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
Other Names:
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.
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Experimental: consolidation chemotherapy group (CNCT group)
concurrent chemoradiotherapy → consolidation chemotherapy → TME (CNCT group)
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Total mesorectal excision
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 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
Other Names:
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.
|
Experimental: induction chemotherapy group (INCT group)
induction chemotherapy → concurrent chemoradiotherapy →TME ( INCT group).
|
Total mesorectal excision
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 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
Other Names:
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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The rate of tumor down-staging
Time Frame: 6-8 months
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Tumor down-staging is considered as Stage yp0-II after surgery, and watch-and-wait strategy after complete clinical response (cCR) was allowed.
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6-8 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of compliance with TNT
Time Frame: 6-8 months
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Rate of compliance with TNT
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6-8 months
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3y OS
Time Frame: 3years
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3-year overall survival (3yOS)
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3years
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3y DFS
Time Frame: 3years
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3-year disease free survival (3yDFS)
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3years
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3y DMFS
Time Frame: 3 years
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3-year distant metastatic free survival(3yDMFS)
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3 years
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3y LRRFS
Time Frame: 3 years
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3-year locoregional recurrence-free survival(3yLRRFS)
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3 years
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EORTC QLQ-C30
Time Frame: 3 years
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EORTC QLQ-C30 to assess the quality of life
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3 years
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EORTC QLQ-CR29
Time Frame: 3 years
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EORTC QLQ-CR29 to assess the quality of life
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3 years
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Wexner continence grading scale
Time Frame: 3 years
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Wexner continence grading scale
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3 years
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CTCAE 4.0
Time Frame: 6-8months
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Severe acute adverse reaction rate(≥III degree)
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6-8months
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Incidence of surgical complications
Time Frame: 6-8 months
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Incidence of surgical complications
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6-8 months
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Collaborators and Investigators
Collaborators
Investigators
- Study Director: Jing Jin, M.D., Chinese Academy of Medical Sciences and Peking Union Medical College
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NCC201809007
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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