| 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
|
|
|
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
|
|
|
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. |