Total Neoadjuvant TreatmentPhase 3TNTCRTNCT03177382
Total Neoadjuvant Treatment vs. Chemoradiotherapy in Local Advanced Rectal Cancer With High Risk Factors
A Phase 3 study testing Total neoadjuvant treatment, concurrent chemoradiotherapy and TME in people with Total Neoadjuvant Treatment and Chemoradiotherapy, run by West China Hospital at 2 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Total Neoadjuvant Treatment, Chemoradiotherapy, Local Advanced Rectal Cancer
- What is being tested?
- Total neoadjuvant treatment, concurrent chemoradiotherapy and TME
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 458 participants
- Where
- 2 sitesChina
- Study dates
- 15 Jun 2017to 30 May 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Inclusion Criteria:（1）Age: 18 ~ 70 years old; sex is not limited. （2）Patients with stage II/III rectal cancer staged under MRI or endoscopic ultrasonography and have at least one risk factor: cT4a-b(resectable)；cT3c-d with EMVI+ (Extramural venous invasion)；cN2；MRF+ (MRI in evaluating the mesorectal fascia).（According to the 2010 AJCC cancer staging system, the seventh edition）. The preoperative T stage is referred to endoscopic ultrasonography or rectal MRI. The N stage is referred to abdominal CT. The M stage is referred to abdominal and thoracic CT. If symptoms occur, other appropriate imaging examinations are needed（cranial MRI or ECT）.
（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.
Exclusion Criteria:（1）Have had prior or concurrent cancer distinct in primary site or histology EXCEPT for curatively treated cervical cancer in situ, Basal cell carcinoma of skin.
（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.
Trial locations and contacts
2 sites in 1 country.
China2 sites, 2 recruiting
- Recruiting
West China Hospital
Chengdu, Sichuan, 610041
Ziqiang Wang, MD
- Not yet recruiting
The Second Affiliated Hospital of Zhejiang University
Hanzhou, Zhejiang, 310009
Kefeng Ding, MD
About this study
Official title: Total Neoadjuvant Treatment Versus Conventional Neo-chemoradiotherapy in Locally Advanced Rectal Cancer With High Risk Factors: a Multicenter Randomized Phase III Clinical Study.
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.
Read more
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.
- Conditions
- Total Neoadjuvant Treatment, Chemoradiotherapy, Local Advanced Rectal Cancer, High Risk Factors
- Being tested
- Total neoadjuvant treatment, concurrent chemoradiotherapy, TME, Adjuvant chemotherapy
- Keywords
- Total Neoadjuvant Treatment, Rectal Cancer, High Risk Factors, Chemoradiotherapy
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Total neoadjuvant treatmentRadiation
Also called TNT
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.
concurrent chemoradiotherapyRadiation
Also called CRT
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.
TMEProcedure or surgery
The TME operation will be given after the end of the neoadjuvant treatment.
Adjuvant chemotherapyDrug
Patients will receive another 6 cycles of CAPOX after TME.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Radiation: Total neoadjuvant treatment; Procedure: 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. Receives: Radiation: concurrent chemoradiotherapy; Procedure: TME; Drug: Adjuvant chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
disease free survival
Time from the completion of the treatment to any recurrences or distant metastases
Measured: 3 years
Secondary outcomes (11)
pathological complete remission rate
The rate of complete remission patients to all resected patients
Measured: 1 months
the 3 year overall survival rate
The rate of patients alive 3 years after the completion of treatment
Measured: 3 years
R0 dissection rate
The rate of patients who received R0 dissection to all the patients
Measured: 1 months
distant metastasis free survival
Time from the completion of the treatment to any distant metastases
Measured: 3 years
local recurrence free survival rate
The rate of patients without local recurrence to all the patients
Measured: 3 years
tumor regression grade (TRG)
The level of tumor regression under pathological examination
Measured: 1 months
the adverse effects during the chemotherapy
Any side effects during the chemotherapy
Measured: 3 months
the operation safety index
The safety index of operation
Measured: 3 months
quality of life
Patients' subjective feeling of life
Measured: 3 years
psychological and cognitive effects
The psychological and cognitive changes of patients after treatment
Measured: 3 years
assessment of nutritional status
The nutritional status of patients
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2017
- Study start15 Jun 2017
- Primary completion30 May 2021 (estimated)
- Study completion30 May 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Total Neoadjuvant TreatmentStudies of the same condition, open and under way.
- More trials run by West China HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 458 participants (estimated)
Sponsor and investigators
- Lead sponsor
- West China Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ziqiang Wang,MD, West China Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03177382
- Sponsor's protocol ID
- TNT-2
- Acronym
- TNTCRT
- Status last verified
- May 2018
- First submitted
- 31 May 2017
- Last updated
- 8 May 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wang X, Tang Y, Lu J, Meng W, Liu P, Zhou J, Wen F, Ding P, Li J, Wang B, Guo Q, Qiu J, Sun H, Deng X, Shen Y, Zeng H, Jiang D, Wang D, Li Y, Xiao Y, Wang Z. Total Neoadjuvant Therapy With Long-Course Radiotherapy Versus Chemoradiotherapy in High-Risk Locally Advanced Rectal Cancer (TNTCRT): A Multicenter, Randomized, Phase III Trial. J Clin Oncol. 2026 Jul 23:JCO2503110. doi: 10.1200/JCO-25-03110. Online ahead of print.
PubMed 42492015
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Total Neoadjuvant Treatment Versus Conventional Neo-chemoradiotherapy in Locally Advanced Rectal Cancer With High Risk Factors: a Multicenter Randomized Phase III Clinical Study.
- ClinicalTrials.gov ID
- NCT03177382
- Acronym / sponsor ID
- TNTCRT / TNT-2
- Conditions
- Total Neoadjuvant Treatment, Chemoradiotherapy, Local Advanced Rectal Cancer, High Risk Factors
- Keywords
- Total Neoadjuvant Treatment, Rectal Cancer, High Risk Factors, Chemoradiotherapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 458 participants (estimated)
- Lead sponsor
- West China HospitalUniversity, hospital or other
- Study start
- 15 Jun 2017 (actual)
- Primary completion
- 30 May 2021 (estimated)
- Study completion
- 30 May 2023 (estimated)
- First posted
- 6 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Total neoadjuvant treatment | Experimental | Radiation: Total neoadjuvant treatment, Procedure: TMEThe 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. |
| concurrent chemoradiotherapy group | Active comparator | Radiation: concurrent chemoradiotherapy, Procedure: TME, Drug: Adjuvant chemotherapyThe 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Total neoadjuvant treatmentAlso: TNTThe 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. | Radiation | Total neoadjuvant treatment |
| concurrent chemoradiotherapyAlso: CRTThe 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 chemoradiotherapy group |
| TMEThe TME operation will be given after the end of the neoadjuvant treatment. | Procedure or surgery | Total neoadjuvant treatment, concurrent chemoradiotherapy group |
| Adjuvant chemotherapyPatients will receive another 6 cycles of CAPOX after TME. | Drug | concurrent chemoradiotherapy group |
Primary outcome
disease free survival
Time frame: 3 years
Time from the completion of the treatment to any recurrences or distant metastases
11 secondary outcomes
pathological complete remission rate
Time frame: 1 months
the 3 year overall survival rate
Time frame: 3 years
R0 dissection rate
Time frame: 1 months
distant metastasis free survival
Time frame: 3 years
local recurrence free survival rate
Time frame: 3 years
tumor regression grade (TRG)
Time frame: 1 months
the adverse effects during the chemotherapy
Time frame: 3 months
the operation safety index
Time frame: 3 months
quality of life
Time frame: 3 years
psychological and cognitive effects
Time frame: 3 years
assessment of nutritional status
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2018.
- Derived from this study: PubMed 42492015Wang X, Tang Y, Lu J, Meng W, Liu P, Zhou J, Wen F, Ding P, Li J, Wang B, Guo Q, Qiu J, Sun H, Deng X, Shen Y, Zeng H, Jiang D, Wang D, Li Y, Xiao Y, Wang Z. Total Neoadjuvant Therapy With Long-Course Radiotherapy Versus Chemoradiotherapy in High-Risk Locally Advanced Rectal Cancer (TNTCRT): A Multicenter, Randomized, Phase III Trial. J Clin Oncol. 2026 Jul 23:JCO2503110. doi: 10.1200/JCO-25-03110. Online ahead of print.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Total neoadjuvant treatment, concurrent chemoradiotherapy and TME in people with Total Neoadjuvant Treatment and Chemoradiotherapy, run by West China Hospital at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ziqiang Wang (+86 28 85422480, wangzqzyh@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
disease free survival (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03177382, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2018.