| CTRI Number |
CTRI/2026/01/100118 [Registered on: 01/01/2026] Trial Registered Prospectively |
| Last Modified On: |
02/06/2026 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Other (Specify) [Randomized Control trial] |
| Study Design |
Other |
|
Public Title of Study
|
This study looks at two different treatment plans given before surgery to find out which works better for patients with high-risk, advanced rectal cancer |
|
Scientific Title of Study
|
Short Course Radiotherapy And FOLFOX/CAPOX versus mFOLFIRINOX And Long Course Chemoradiation as Total Neoadjuvant Therapy In High-Risk Locally Advanced Rectal Cancers – A Phase III Randomized Control trial |
| Trial Acronym |
PRAGMATIC TNT |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Anant Ramaswamy |
| Designation |
Professor and Medical Oncologist |
| Affiliation |
Tata Memorial Hospital |
| Address |
1102 Homibhabha Building Tata Memorial Hospital Dr Ernest Borges Parel Mumbai
1102 Homibhabha Building Tata Memorial Hospital Dr Ernest Borges Parel Mumbai
Mumbai
MAHARASHTRA
400012
India |
| Phone |
09833034802 |
| Fax |
|
| Email |
anantr13@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Anant Ramaswamy |
| Designation |
Professor and Medical Oncologist |
| Affiliation |
Tata Memorial Hospital |
| Address |
1102 Homibhabha Building Tata Memorial Hospital Dr Ernest Borges Parel Mumbai
1102 Homibhabha Building Tata Memorial Hospital Dr Ernest Borges Parel Mumbai
Mumbai
MAHARASHTRA
400012
India |
| Phone |
09833034802 |
| Fax |
|
| Email |
anantr13@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Anant Ramaswamy |
| Designation |
Professor and Medical Oncologist |
| Affiliation |
Tata Memorial Hospital |
| Address |
1102 Homibhabha Building Tata Memorial Hospital Dr Ernest Borges Parel Mumbai
1102 Homibhabha Building Tata Memorial Hospital Dr Ernest Borges Parel Mumbai
Mumbai
MAHARASHTRA
400012
India |
| Phone |
09833034802 |
| Fax |
|
| Email |
anantr13@gmail.com |
|
|
Source of Monetary or Material Support
|
| Tata Memorial Hospital, Dr. Ernest Borges Road, Parel,Mumbai-400012 , maharashtra ,India |
|
|
Primary Sponsor
|
| Name |
Tata Memorial Hospital |
| Address |
Tata Memorial Hospital DrErnest Borges road Parel Mumbai 4000012 |
| Type of Sponsor |
Research institution and hospital |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 2 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Lincoln Pujari |
Mahamana Pandit Madan Mohan Malaviya Cancer Centre |
Banaras Hindu University, Campus, Sundar Bagiya Colony, Sundarpur, Varanasi, Uttar Pradesh, 221005.
Varanasi
UTTAR PRADESH |
7735661666
lincoln.pujari@gmail.com |
| Dr Anant Ramaswamy |
Tata Memorial Hospital, Mumbai |
3rd floor,Homi Bhabha Block, Tata Memorial Hospital, Dr Ernest Borges Road, Parel, Mumbai 400012
Mumbai
MAHARASHTRA |
9833034802
anantr13@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 2 |
| Name of Committee |
Approval Status |
| Institutional ethics committee MPMMCC Varanasi |
Approved |
| Tata Memorial Hospital Institutional Ethics Committee-I |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C20||Malignant neoplasm of rectum, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
mFOLFIRINOX And Long Course Chemoradiation as Total Neoadjuvant Therapy |
The patients will receive neoadjuvant chemotherapy with mFOLFIRINOX for 4 cycles followed by Long course chemoradiation (LCRT) after a 2-3 weeks gap. Post completion of LCRT, patients will receive 2 cycles of mFOLFIRINOX (after a gap of 2-3 weeks) |
| Comparator Agent |
Short Course Radiotherapy And FOLFOX or CAPOX |
The patients will receive short course radiation (25 Gy divided over 5 fractions) followed by neoadjuvant chemotherapy for 4 months, either CAPOX or mFOLFOX |
|
|
Inclusion Criteria
|
| Age From |
18.00 Day(s) |
| Age To |
90.00 Year(s) |
| Gender |
Both |
| Details |
Adults of either sex aged more than 18 years who are willing to provide written informed consent.
Histologically confirmed rectal adenocarcinoma located within less than 15 centimeters from the anal verge.
Eastern Cooperative Oncology Group performance status of 0, 1, or 2.
Presence of at least one high-risk feature, including cT3 disease with mesorectal fascia involvement, cT4 disease, extramural vascular invasion, signet ring cell carcinoma or poorly differentiated adenocarcinoma in node-positive or T3 and above disease, or presence of lateral pelvic lymph nodes on pelvic magnetic resonance imaging.
Tumors considered resectable or potentially resectable after chemoradiation and patients who are medically fit for surgery.
Use of adequate contraception in patients of reproductive potential, with a negative pregnancy test required for women of childbearing potential.
Adequate hematological, liver, and renal function at the time of study inclusion. |
|
| ExclusionCriteria |
| Details |
Patients meeting any of the following criteria will be excluded from the study:
Patients with distant metastases, including para aortic lymph nodes. Para aortic node negativity must be confirmed by radiological or histological assessment before study consideration.
Patients suitable for a PROSPECT type neoadjuvant approach, including upper or mid rectal T3 tumors without mesorectal fascia involvement, limited nodal disease, no lateral pelvic nodes, and no extramural vascular invasion.
Patients with signet ring rectal adenocarcinoma staged as T3 N0 without extramural vascular invasion or lateral pelvic lymph nodes.
Patients with low rectal adenocarcinoma who are candidates for intersphincteric resection or non operative management such as a wait and watch approach, as determined by the multidisciplinary team prior to screening.
Patients with microsatellite instability high tumors.
Patients with rectal cancer histology other than adenocarcinoma.
Patients with a history of coronary artery disease, including angina or myocardial infarction.
Patients with known homozygous dihydropyrimidine dehydrogenase deficiency.
Patients with grade two or higher sensory or motor neuropathy.
Patients with known hypersensitivity or contraindications to any study related medication.
Patients with another active malignancy or a past history of malignancy, except for treated carcinoma in situ of the cervix or basal cell carcinoma of the skin.
Patients with human immunodeficiency virus, hepatitis B, or hepatitis C infection requiring active antiviral therapy at screening.
Pregnant or breastfeeding women.
Patients with active progressive infection or any other serious medical condition that may interfere with study treatment. |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| The primary objective of the study is to evaluate whether total neoadjuvant therapy using modified FOLFIRINOX chemotherapy followed by long course chemoradiation improves outcomes compared with short course radiotherapy followed by modified FOLFOX or CAPOX chemotherapy, as measured by three year event free survival. |
Primary Objective will be measured by event-free survival at 3 years from the time of randomization. |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Pathological Complete Response (pCR) rates |
pCR rate is defined as the percentage of patients, relative to the total of enrolled subjects, achieving complete histological regression with no available tumor cells ypT0N0. This will be measured by the MANDARD criteria. In brief, the Mandard scoring is as follows
TRG1—No residual tumor, presence of fibrosis; TRG2—Rare residual tumor cells scattered through fibrosis; TRG3—Increased residual tumor cells but fibrosis is predominant; TRG4—Residual tumor cells outgrowing fibrosis; TRG5—Absence of regression
Patients with a TRG1 score will be considered to have achieved a pCR.
|
| R0 resection rates |
R0 resection rate is defined as the percentage of patients, relative to the total of enrolled subjects, undergoing R0 resection of the primary tumor after the commencement of neoadjuvant therapy. |
| Local Recurrence-free Survival at 3 years |
from randomization to local or locoregional progression (either at primary or nodal sites), without appearance of concurrent distant metastases. Patients who have concurrent distant metastases will be classified otherwise |
| Overall Survival at 3 years |
OS is defined as the time from randomization to the time of occurrence of death |
| To compare toxicities for both the arms |
according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0, postoperative complication rate, and late toxicity rate at 1 year after surgery. |
|
|
Target Sample Size
|
Total Sample Size="678"
Sample Size from India="678"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
10/12/2026 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="8"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
Brief Summary
Modification(s)
|
The PRAGMATIC TNT Study is a Phase Three randomized clinical trial designed to compare two different total neoadjuvant treatment approaches for patients with high risk, locally advanced rectal cancer. Total neoadjuvant therapy involves giving chemotherapy and radiation therapy before surgery to shrink the tumor and improve outcomes. In this study, participants are randomly assigned to receive either short course radiotherapy followed by chemotherapy, or chemotherapy followed by long course chemoradiation. After completing the assigned treatment, all patients will undergo surgery to remove the tumor and will be followed for approximately three years. The primary outcome of the study is event free survival, which measures the time patients remain free from cancer progression or recurrence. The study also aims to assess whether blood based tests can help guide treatment decisions after surgery. By comparing these two treatment strategies, the study seeks to identify the most effective approach and improve long term outcomes for patients with rectal cancer. |