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

Sponsor
Chinese Academy of Medical Sciences (Other)
Overall Status
Recruiting
CT.gov ID
NCT04543695
Collaborator
Peking University Cancer Hospital & Institute (Other), Peking Union Medical College Hospital (Other), Jilin Provincial Tumor Hospital (Other), Cancer Hospital of Guizhou Province (Other), Xijing Hospital (Other)
255
Enrollment
1
Location
3
Arms
35
Anticipated Duration (Months)
7.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
Phase 2

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 T3,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 (experimental group);Or group 3: induction chemotherapy → concurrent chemoradiotherapy →TME ( experimental group).The primary end point is the rate of tumor down-staging, which is defined as stage yp0-II after surgery. 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 Design

Study Type:
Interventional
Anticipated Enrollment :
255 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Prospective, Multicenter, Randomized Controlled Trial of Neoadjuvant Therapy for High-risk Locally Advanced Rectal Cancer
Actual Study Start Date :
Jul 1, 2020
Anticipated Primary Completion Date :
Jun 1, 2023
Anticipated Study Completion Date :
Jun 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: adjuvant chemotherapy group

concurrent chemoradiotherapy → TME → adjuvant chemotherapy (control group)

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
Other Names:
  • CAOPX

    • Drug: 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
    Experimental: consolidation chemotherapy group

    concurrent chemoradiotherapy → consolidation chemotherapy → TME (experimental group)

    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
    Other Names:
  • CAOPX

    • Drug: 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
    Experimental: induction chemotherapy group

    induction chemotherapy → concurrent chemoradiotherapy →TME ( experimental group).

    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
    Other Names:
  • CAOPX

    • Drug: 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

    Outcome Measures

    Primary Outcome Measures

    1. The rate of tumor down-staging [6-8 months]

      Tumor down-staging is considered as Stage yp0-II after surgery.

    Secondary Outcome Measures

    1. Rate of compliance with TNT [6-8 months]

      Rate of compliance with TNT

    2. 3y OS [3years]

      3-year overall survival (3yOS)

    3. 3y DFS [3years]

      3-year disease free survival (3yDFS)

    4. 3y DMFS [3 years]

      3-year distant metastatic free survival(3yDMFS)

    5. 3y LRRFS [3 years]

      3-year locoregional recurrence-free survival(3yLRRFS)

    6. EORTC QLQ-C30 [3 years]

      EORTC QLQ-C30 to assess the quality of life

    7. EORTC QLQ-CR29 [3 years]

      EORTC QLQ-CR29 to assess the quality of life

    8. Wexner continence grading scale [3 years]

      Wexner continence grading scale

    9. CTCAE 4.0 [6-8months]

      Severe acute adverse reaction rate（≥III degree）

    10. Incidence of surgical complications [6-8 months]

      Incidence of surgical complications

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China 100021

    Sponsors and Collaborators

    • Chinese Academy of Medical Sciences
    • Peking University Cancer Hospital & Institute
    • Peking Union Medical College Hospital
    • Jilin Provincial Tumor Hospital
    • Cancer Hospital of Guizhou Province
    • Xijing Hospital

    Investigators

    • Study Director: Jing Jin, M.D., Chinese Academy of Medical Sciences and Peking Union Medical College

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Jing Jin, M.D., Clinical Professor，Radiotherapy Department, Chinese Academy of Medical Sciences
    ClinicalTrials.gov Identifier:
    NCT04543695
    Other Study ID Numbers:
    • NCC201809007
    First Posted:
    Sep 10, 2020
    Last Update Posted:
    Feb 7, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Jing Jin, M.D., Clinical Professor，Radiotherapy Department, Chinese Academy of Medical Sciences
    Rectal Cancer
    Radiotherapy
    High Risk
    Total Neoadjuvant Therapy
    Additional relevant MeSH terms:
    Rectal Neoplasms

    Study Results

    No Results Posted as of Feb 7, 2022