NCT03177382

Brief Summary

Purpose:To compare the efficacy and the safety of total neoadjuvant chemotherapy + TME with standard neoadjuvant concurrent chemoradiotherapy + TME + adjuvant chemotherapy for locally advanced rectal cancer patients with high risk factors of recurrence. Evaluation indexes: (1) the primary evaluation index: disease-free survival (disease free survival, DFS); (2) the secondary evaluation indexes: pathological complete remission rate (pCR), the 3 year overall survival (overall survival, OS); R0 dissection rate; distant metastasis free survival (DMFS); local recurrence free survival rate (LRRFS); tumor regression grade (TRG, tumor regression grade) and the adverse reaction rate during the chemotherapy, the operation safety index; quality of life; psychological and cognitive effects, assessment of nutritional status. Safety evaluation indexes: including all adverse events observed during the experiment. Number of patients: 458 cases Study design: patients will be randomly assigned into the total neoadjuvant treatment group (experimental group, TNT) and neoadjuvant concurrent chemotherapy group (control group, CRT) in the ratio of 1: 1. The patients of experimental group will be given 1 cycle of induction CAPOX (Oxaliplatin 130mg/m2 d1, Capecitabine 1000mg/m2, bid, d1-14) prior to radiotherapy. Then pelvic IMRT/VMAT (50-50.4Gy/25-28f) and two cycles of concurrent chemotherapy (Oxaliplatin 130mg/m2, d1, d 22, Capecitabine 825mg/m2, bid, 5d/w, 25-28d) are performed. And three cycles of consolidation chemotherapy (CAPOX) are delivered after concurrent chemoradiotherapy. Total mesorectal excision (TME) is performed after completion of the whole neoadjuvant treatment. The patients of control group will receive standard concurrent neoadjuvant chemoradiotherapy with capecitabine (825mg/m2, bid, 5d/w) followed by TME 6-8 weeks after the end of concurrent chemoradiotherapy. Then, patients are treated with another 6 cycles of CAPOX. Schedule: Investigators plan to finish the study in 4 years and write the related work within 2 years after the completion of this study.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
458

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Jun 2017

Longer than P75 for phase_3

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 31, 2017

Completed
6 days until next milestone

First Posted

Study publicly available on registry

June 6, 2017

Completed
9 days until next milestone

Study Start

First participant enrolled

June 15, 2017

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 30, 2021

Completed
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 30, 2023

Completed
Last Updated

May 8, 2018

Status Verified

May 1, 2018

Enrollment Period

4 years

First QC Date

May 31, 2017

Last Update Submit

May 4, 2018

Conditions

Total Neoadjuvant TreatmentChemoradiotherapyLocal Advanced Rectal CancerHigh Risk Factors

Keywords

Total Neoadjuvant TreatmentRectal CancerHigh Risk FactorsChemoradiotherapy

Outcome Measures

Primary Outcomes (1)

  • disease free survival

    Time from the completion of the treatment to any recurrences or distant metastases

    3 years

Secondary Outcomes (11)

  • pathological complete remission rate

    1 months

  • the 3 year overall survival rate

    3 years

  • R0 dissection rate

    1 months

  • distant metastasis free survival

    3 years

  • local recurrence free survival rate

    3 years

  • +6 more secondary outcomes

Study Arms (2)

Total neoadjuvant treatment

EXPERIMENTAL

The interventions of experimental group include 1 cycle of CAPOX before radiotherapy; and then start concurrent chemoradiotherapy with CAPOX regimen (capecitabine: 825mg/m2, bid, 5d/w; oxaliplatin, 130mg/m2, D1, q3w) for 2 cycles followed by 3 cycles of CAPOX 2-3 weeks after the completion of radiotherapy. Intensity modulated radiotherapy (IMRT/VMAT) was used for radiotherapy, and the dose was 50-50.4Gy/25-28f, 1.8-2.0Gy/d, 5f/w. The TME operation will be given 3-4 weeks after the end of the total neoadjuvant treatment.

Radiation: Total neoadjuvant treatmentProcedure: TME

concurrent chemoradiotherapy group

ACTIVE COMPARATOR

The interventions of control group is standard preoperative concurrent chemoradiotherapy. The radiotherapy target areas and dosage are the same as group TNT. During radiotherapy, only oral capecitabine will be delivered and capecitabine dose was 825mg/m2, bid, 5d/w. The TME surgery will be performed 6-8 weeks after the end of concurrent chemoradiotherapy. Then, patients will receive another 6 cycles of CAPOX.

Radiation: concurrent chemoradiotherapyProcedure: TMEDrug: Adjuvant chemotherapy

Interventions

Total neoadjuvant treatmentRADIATION

The interventions of experimental group include 1 cycle of CAPOX before radiotherapy; and then start concurrent chemoradiotherapy with CAPOX regimen (capecitabine: 825mg/m2, bid, 5d/w; oxaliplatin, 130mg/m2, D1, q3w) for 2 cycles followed by 3 cycles of CAPOX 2-3 weeks after the completion of radiotherapy. Intensity modulated radiotherapy (IMRT/VMAT) was used for radiotherapy, and the dose was 50-50.4Gy/25-28f, 1.8-2.0Gy/d, 5f/w.

Also known as: TNT
Total neoadjuvant treatment
concurrent chemoradiotherapyRADIATION

The interventions of control group is standard preoperative concurrent chemoradiotherapy. The radiotherapy target areas and dosage are the same as group TNT. During radiotherapy, only oral capecitabine will be delivered and capecitabine dose was 825mg/m2, bid, 5d/w. The TME surgery will be performed 6-8 weeks after the end of concurrent chemoradiotherapy. Then, patients will receive another 6 cycles of CAPOX.

Also known as: CRT
concurrent chemoradiotherapy group
TMEPROCEDURE

The TME operation will be given after the end of the neoadjuvant treatment.

Total neoadjuvant treatmentconcurrent chemoradiotherapy group
Adjuvant chemotherapyDRUG

Patients will receive another 6 cycles of CAPOX after TME.

concurrent chemoradiotherapy group

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • （3）The lower edge of lesion is less than 12cm from anal verge according to rigid sigmoidoscopy or rectal digital examination.
  • （4）No distant metastasis after a thorough examination . （5）Pathological diagnosis of rectal adenocarcinoma. （6）ECOG score: 0-1. （7）Patients with primary rectal cancer who had not received surgery prior to surgery (except for palliative ileostomy or colostomy), radiotherapy, systemic chemotherapy or other anti-tumor therapy.
  • （8）The main organ function is normal, including the following characteristics:
  • Blood routine examination: HB ≥9g/dL, WBC ≥ 3.5/4.0×109/L，PLT≥ 100×109/L
  • Biochemical examination：Crea and BIL ≤ 1.0 upper normal limit（ULN），ALT and AST≤ 2.5 upper normal limit（ULN）.
  • （9）Not allergic to 5-Fu or Platinum. （10）The site of radiotherapy had not previously received radiation. （11）If female and of childbearing potential, have a negative result on a pregnancy test performed a maximum of 7 days before initiation of study treatment. If female and of childbearing potential, or if male, agree to use adequate contraception (eg, abstinence, intrauterine device, oral contraceptive, or double-barrier method) based on the judgment of the investigator or a designated associate from the date on which the ICF (Informed Consent Form) is signed until 8 weeks after the last dose of study drug.
  • （12）Participants are volunteered to participate in this study, sign informed consent, good compliance, cooperation with follow-up.

You may not qualify if:

  • （2）Pregnant or lactating women. （3）Patients with severe cardiovascular disease and poorly controlled diabetes. （4）Mental disorder. （5）Severe infection. （6）Patients who can't finish MRI examination. （7）Patients were treated with thrombolytic therapy and anticoagulant therapy, either with bleeding diathesis or coagulopathy, or aneurysm, stroke, transient ischemic attack, arteriovenous malformation in the past year.
  • （8）The past history of kidney disease, urine or urine protein found in clinical renal abnormalities.
  • （9）The digestive tract fistula, perforation or serious ulcer disease. （10）Be allergic to 5-Fu or Platinum. （11）The presence of severe gastrointestinal diseases that affecting the absorption of oral chemotherapy drugs.
  • （12）Additional clinical trials were attended within 4 weeks before treatment initiation.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

West China Hospital

Chengdu, Sichuan, 610041, China

RECRUITING

The Second Affiliated Hospital of Zhejiang University

Hanzhou, Zhejiang, 310009, China

NOT YET RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

TrinitrotolueneChemoradiotherapyChemotherapy, Adjuvant

Condition Hierarchy (Ancestors)

Colorectal NeoplasmsIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

TolueneBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsCombined Modality TherapyTherapeuticsDrug TherapyRadiotherapy

Central Study Contacts

Ziqiang Wang

CONTACT

+86 28 85422480wangzqzyh@163.com

Xin Wang

CONTACT

+86 28 85423609wangxin213@sina.com

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

May 31, 2017

First Posted

June 6, 2017

Study Start

June 15, 2017

Primary Completion

May 30, 2021

Study Completion

May 30, 2023

Last Updated

May 8, 2018

Record last verified: 2018-05

Data Sharing

IPD Sharing
Will not share

Locations

CN(2)