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CTRI Number  CTRI/2021/05/033642 [Registered on: 17/05/2021] Trial Registered Prospectively
Last Modified On: 18/01/2022
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   Outcome of patient receiving additional chemotherapy after chemoradiotherapy for locally advanced rectal carcinoma compared to those receiving only chemoradiotherapy 
Scientific Title of Study   Total Neoadjuvant Therapy for Locally Advanced Rectal Carcinoma: A Multicentric Randomized Controlled Trial 
Trial Acronym  TNT-LARC 
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Ravi Shankar Biswas 
Designation  Assistant Professor 
Affiliation  Medical College, Kolkata 
Address  Department of Surgical Gastroenterology Green Building, First Floor 88, College Street Kolkata

Kolkata
WEST BENGAL
700073
India 
Phone  9874338353  
Fax    
Email  drrsbiswas1@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Ravi Shankar Biswas 
Designation  Assistant Professor 
Affiliation  Medical College, Kolkata 
Address  Department of Surgical Gastroenterology Green Building, First Floor 88, College Street Kolkata

Kolkata
WEST BENGAL
700073
India 
Phone  9874338353  
Fax    
Email  drrsbiswas1@gmail.com  
 
Details of Contact Person
Public Query
 
Name  Dr Ravi Shankar Biswas 
Designation  Assistant Professor 
Affiliation  Medical College, Kolkata 
Address  Department of Surgical Gastroenterology Green Building, First Floor 88, College Street Kolkata

Kolkata
WEST BENGAL
700073
India 
Phone  9874338353  
Fax    
Email  drrsbiswas1@gmail.com  
 
Source of Monetary or Material Support  
Medical College Kolkata 88, College Street Kolkata 700073 
 
Primary Sponsor  
Name  Medical College Kolkata 
Address  88 College Street kolkata 700073 
Type of Sponsor  Government medical college 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Ravi Shankar Biswas  Medical College Kolkata  Department of Surgical Gastroenterology Green Building First Floor 88 College Street
Kolkata
WEST BENGAL 
9874338353

drrsbiswas1@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institute Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: C20||Malignant neoplasm of rectum,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Chemoradiotherapy  50.4 Gy, 28 fraction radiotherapy with Capecitabine (825 mg/m2 twice daily, 5 days a week) 
Intervention  Chemoradiotherapy followed by Capecitabine and oxaliplatin  Three cycles of Capecitabine and Oxaliplatin will be administered 2 weeks after completion of neoadjuvant chemoradiotherapy (50.4 Gy radiation with Capecitabine-825 mg/m2 twice daily, 5 days a week )  
 
Inclusion Criteria  
Age From  16.00 Year(s)
Age To  75.00 Year(s)
Gender  Both 
Details  1. Clinically and radiologically stage T3 and T4 rectal carcinoma.
2. Any T stage with lymph node positive on imaging.
3. Tumour located within 12cm of anal verge.
4. ECOG performance scale 0-2 
 
ExclusionCriteria 
Details  1. Metastatic disease
2. History of previous pelvic irradiation or
chemotherapy for rectal carcinoma.
3. Synchronous malignancy.
4. Associated colonic polyposis.
5. Obvious or suspected intestinal obstruction
(eligible if proximal diversion stoma
relieved the obstruction).
6. Any serious medical comorbid condition that
precludes systemic therapy.
7. Previously treated for other malignancy
except for non-melanoma skin cancer.
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
To compare the rate of pathological complete response in both arm.  During the histopathological examination specimen of definitive surgery. 
 
Secondary Outcome  
Outcome  TimePoints 
Overall survival and recurrence free survival  After 1 year of definitive surgery 
Chemotoxicity due to added consolidation chemotherapy  After completion of chemotherapy 
Radiological response of tumour to neoadjuvant therapy  12 weeks after completion of chemoradiotherapy in comparative arm and 4 weeks after completion of chemotherapy in intervention arm  
 
Target Sample Size   Total Sample Size="258"
Sample Size from India="258" 
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/ Phase 4 
Date of First Enrollment (India)   01/07/2021 
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="4"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   NIL 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary  

Colorectal cancer is one of the fastest-growing and increasingly reported neoplasms in India, and the rectum is the most common subsite. In India, it’s the fourth most common cause of cancer in males (6.4%) and fifth most common cause of cancer in female (3.4%). Patients having locally advanced rectal carcinoma (LARC) especially with clinical subset T3 or T4 are at high risk of both local recurrence and distant metastasis. These patients are managed with a multidisciplinary approach and preoperatively fluoropyrimidine (5-fluorouracil or capecitabine) based chemo-radiotherapy followed by total meso-rectal excision (TME) has become the standard of care in LARC. Although there is a decrease in local recurrence, the improvement in overall survival is still unclear. Trial have failed to show any improvement with an intensification of chemotherapy and sequencing it with radiotherapy around surgery. Despite increased toxicity, there is no survival benefit following the addition of oxaliplatin on concurrent fluoropyrimidine in preop CRT. To avoid the toxicity of adjuvant chemotherapy, it has been suggested to add induction chemotherapy before CRT, but it fails to improve any survival benefit compared to standard therapy. Studies have shown that Capecitabine and oxaliplatin combination in an adjuvant setting, is safe and feasible in patients with LARC. The addition of Capecitabine and oxaliplatin as consolidation chemotherapy has shown to be beneficial in terms of pathological complete response and early initiation of systemic therapy. Other benefits include reduced chances of a positive distal resection margin, early treatment of micro-metastasis, de-escalation of adjuvant therapy, and early closure of proximal diversion stoma.

 
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