| CTRI Number |
CTRI/2024/11/076896 [Registered on: 18/11/2024] Trial Registered Prospectively |
| Last Modified On: |
15/12/2025 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug
Radiation Therapy |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
A Study Comparing Three-Drug Chemotherapy with Chemotherapy and Radiation Before Surgery in Patients with Advanced but Operable Esophageal Cancer |
|
Scientific Title of Study
|
Phase III RCT comparing triplet neoadjuvant chemotherapy with neoadjuvant chemoradiation in patients with locally advanced resectable esophageal squamous carcinoma |
| Trial Acronym |
-- |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Minit Shah |
| Designation |
Associate Professor |
| Affiliation |
Tata Memorial Hospital |
| Address |
Tata Memorial Hospital,
Homi Bhabha Block, Department of Medical oncology, Room no 204, 2nd floor, Dr Ernest Borges Rd, Parel East, Mumbai
Mumbai
MAHARASHTRA
400012
India |
| Phone |
7021620792 |
| Fax |
-- |
| Email |
minitjshah@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Minit Shah |
| Designation |
Associate Professor |
| Affiliation |
Tata Memorial Hospital |
| Address |
Tata Memorial Hospital,
Homi Bhabha Block, Department of Medical oncology, Room no 204, 2nd floor, Dr Ernest Borges Rd, Parel East, Mumbai
Mumbai
MAHARASHTRA
400012
India |
| Phone |
7021620792 |
| Fax |
-- |
| Email |
minitjshah@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Minit Shah |
| Designation |
Associate Professor |
| Affiliation |
Tata Memorial Hospital |
| Address |
Tata Memorial Hospital,
Homi Bhabha Block, Department of Medical oncology, Room no 204, 2nd floor, Dr Ernest Borges Rd, Parel East, Mumbai
Mumbai
MAHARASHTRA
400012
India |
| Phone |
7021620792 |
| Fax |
-- |
| Email |
minitjshah@gmail.com |
|
|
Source of Monetary or Material Support
|
| Tata Memorial Hospital, Dr E Borges Road, Parel, Mumbai-400012 |
|
|
Primary Sponsor
|
| Name |
Tata Memorial Hospital |
| Address |
Tata Memorial Hospital, Homi Bhabha Block, Parel East, Mumbai- 400012 |
| Type of Sponsor |
Research institution and hospital |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| Not Applicable |
NA |
|
|
Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 3 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Syed Nisar Ahmad |
Sher i kashmir Institute of medical sciences |
Room 103 ist floor SCI building Sher i kashmir institute of medical sciences (SKIMS) soura Srinagar J&K 190011
Srinagar
JAMMU & KASHMIR |
95416 66516
syednisar76@yahoo.co.in |
| Dr Minit Shah |
Tata Memorial Hospital |
Homi Bhabha Block, Department of Medical oncology, Room no 204, 2nd floor, Dr Ernest Borges Rd, Parel East, Mumbai-400012
Mumbai
MAHARASHTRA |
7021620792
--
minitjshah@gmail.com |
| Dr BhaveshPoladia |
Thangam Hospital |
Clinical Research, A Block, Upper
Basement(Room No:1506), Thangam
Hospital and Thangam Cancer Center,
No: 54, Dr. Sankaran Road, Namakkal
- 637001, Tamilnadu, India
Namakkal
TAMIL NADU
Namakkal
TAMIL NADU |
9819151554
bhaveshpoladia@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 3 |
| Name of Committee |
Approval Status |
| Sher-i-Kashmir Institute of Medical Sciences, Srinagar |
Approved |
| Tata Memorial Centre Institutional Ethics Committee-I |
Approved |
| Thangam Hospital Institutional Ethics Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C15||Malignant neoplasm of esophagus, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Concurrent Chemoradiation will be given.
Radiotherapy: All patients will be treated with conformal radiotherapy, either 3DCRT or IMRT with IGRT.Total radiation dose planned will be 41.4Gy, administered at 1.8 Gy/ day in 23 fractions.
Chemotherapy:
chemotherapy will be carboplatin AUC 2 (calculated by Calvert formula) and paclitaxel 50 mg/m2. |
Concurrent chemotherapy will be carboplatin AUC 2 (calculated by Calvert formula) and paclitaxel 50 mg/m2. Patients will receive appropriate hydration (500mL sodium chloride 0.9% non-PVC infusion bag with a 0.22 micron in-line filter for paclitaxel chemotherapy), anti-emetics (Tab. Aprepitant 125 mg orally pre-chemotherapy, then 80 mg orally on days 2 and 3, Inj. Granisetron 1mg intravenously, Inj. Promethazine 12.5 mg intravenously, Inj. Dexamethasone 8 mg intravenously pre-chemotherapy) and other supportive care medications. On days 1, 8, 15, 22 and 29, chemotherapy is administered. A total dose of 41.4 Gy was given in 23 fractions of 1.8 Gy each, with 5 fractions administered per week, starting on the first day of the first chemotherapy. The patients undergo surgery as soon as possible after completion of chemo-radiotherapy, preferably within 4 to 6 weeks. Concurrent chemotherapy will be started between days 1 to 5 of the start of radiotherapy and administered weekly as long as radiotherapy continues. Adjuvant treatment will be as per standard institutional protocol. |
| Intervention |
Docetaxel, Cisplatin/Carboplatin and 5-FU/Capecitabine |
5FU will be dosed at 750 mg/m2 continuous intravenous infusion on days 1 to 5. Cisplatin will be dosed at 75 mg/m2on day 1 of each cycle, diluted in 500ml of 0.9% normal saline (with appropriate pre- and post-chemotherapy hydration, and anti-emetic measures). Carboplatin AUC 5 or 6 (calculated by Calvert formula) will be administered intravenous, in 250-500ml 0.9%NS or dextrose solutions over 30-60mins on Day 1. Docetaxel will be dosed at 75mg/m2 intravenous on day 1. (500mL sodium chloride 0.9% non-PVC infusion bag with a 0.22 micron in-line filter).Capecitabine will be dosed at 650mg/m2, twice a day, daily, every 21-days, starting on day 1 of chemotherapy. The patients will undergo surgery as soon as possible after completion of chemotherapy. Chemotherapy will be administered every 21 days for 3-4 cycles. Adjuvant treatment will be as per standard institutional protocol. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
75.00 Year(s) |
| Gender |
Both |
| Details |
1. Subjects must have histologically proven squamous cell carcinoma of the esophagus or esophagogastric junction
2. Tumour should be surgically resectable. Pre-treatment stage cT24a, N0-3, M0. Cervical esophageal cancers should be resectable without the need for laryngectomy.
3. Male or female or Transgender subjects aged 18-75 years of age.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
5. Subjects must have normal organ and marrow function
6. Patients with HIV are potentially eligible, as long as they have a CD4 count more than 200, are on concurrent HAART highly active antiretroviral therapy, and absence of active AIDS defining conditions.
7. Negative serum or urine pregnancy test at screening for women of childbearing potential.
8. Women of childbearing potential must be willing to consent to using effective contraception
9. Both men and women of all races and ethnic groups are eligible for this study.
10. Ability to understand and the willingness to sign a written informed consent document. |
|
| ExclusionCriteria |
| Details |
1. Subjects who are receiving any other concurrent investigational agents.
2. Clinical or radiologic evidence of metastatic disease.
3. Patients unfit for curative surgery for any reason.
4. Infections Active infection requiring systemic therapy.
5. Hepatitis B virus or hepatitis C virus infection at screening positive HBV surface antigen with a raised HBV DNA or anti HCV antibody screening test positive with raised HCV RNA. Mere presence of HBV or HCV at screening test will not rule the patient out.
6. Hypersensitivity to study drug Known prior severe hypersensitivity to investigational product or any component in its formulations.
7. Clinically significant cardiovascular disease unstable angina, congestive heart failure
8. Other severe acute or chronic medical conditions including inflammatory bowel disease, pneumonitis, chronic kidney disease, known peripheral neuropathy more than grade 1
9. Pregnant women are excluded from this study
10. Any other malignancies within the last 5 years other than curatively treated basal cell carcinoma of the skin and or in situ carcinoma of the cervix. |
|
|
Method of Generating Random Sequence
|
Stratified block randomization |
|
Method of Concealment
|
On-site computer system |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Overall survival (OS) |
At death |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
PFS
ORR
Toxicity
QOL
R zero Resection rates Pathological response rates Tumour regression grades Peri and postoperative complication rates patterns of treatment failure local vs locoregional vs distant
Factors that impact OS Gender ECOG baseline body weight baseline haemoglobin baseline albumin histopathological grade Axial Imaging
Factors that impact PFS Gender ECOG baseline body weight baseline haemoglobin baseline albumin histopathological grade Axial Imaging |
1. At progression
2. At progression
3. every visit
4. QOL for Arm A At baseline, week 5 of chemoradiation, first follow up visit post chemoradiation completion, first follow up visit post-surgery, 2 months , 4 months
|
|
|
Target Sample Size
|
Total Sample Size="404"
Sample Size from India="404"
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)
|
25/11/2024 |
| 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="5"
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
|
Aim:
To evaluate the efficacy and impact on overall
survival with 3-drug neoadjuvant chemotherapy compared to neoadjuvant
chemoradiation in patients with locally
advanced resectable esophageal squamous carcinoma. Primary
objective:
To compare the Overall Survival (OS) in all patients
receiving triplet neoadjuvant chemotherapy versus neoadjuvant chemoradiation in
patients with locally advanced resectable
esophageal squamous carcinoma. Secondary
objectives: To compare Progression Free Survival (PFS)
To compare the best overall response rate
(ORR) according to the Response
Evaluation Criteria in Solid Tumours (RECIST) version 1.1 To assess and compare the safety and tolerability To compare the quality of life (QOL) To assess R0 Resection rates, Pathological
response rates, Tumour regression grades, Peri- and post-operative complication
rates, patterns of treatment failure, factors impacting OS and PFS Tertiary objective: Exploring Biomarkers Study
Design
Phase III, Double arm, Open Label, Randomized Controlled
Non-Inferiority Study. Study
Setting
The study would be conducted by the Department of Medical
Oncology, in the Thoracic Medical Oncology Unit. Patients seen in Thoracic
Medical Oncology DMG at TMH or ACTREC would be eligible for participation.
Patients sent for the study would be consented and post consenting would be
screened for this study. Patients subjected to selection criteria (detailed in
eligibility criteria) will be eligible for this study. Eligibility
Criteria
Patients will be assessed for the below mentioned
eligibility criteria prior to inclusion in the study. Sample
size
Assuming a 5-year OS of 50% in the CROSS arm (JCO 2021
update), type 1 error of 5% (one sided), type 2 error of 10%, 1:1
randomisation, 10% lost to follow up and non-inferiority margin of 13% (upper
95% CI of the delta), the sample size required is 404. Sequence
generation Stratified randomisation with block size of 4 will be
performed. The following stratification factors will be accounted: Age (≥60 years versus <60 years)
Eastern Cooperative Oncology Group Performance
Status 0 or 1 versus 2.
|