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CTRI Number  CTRI/2024/03/064939 [Registered on: 28/03/2024] Trial Registered Prospectively
Last Modified On: 19/08/2026
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   Study to compare chemotherapy versus chemotherapy plus immunotherapy in esophageal cancer 
Scientific Title of Study   Phase III RCT comparing chemotherapy to chemotherapy plus immunotherapy in patients with advanced esophageal squamous cell cancer receiving first line palliative intent systemic therapy (NICE Study). 
Trial Acronym  NIL 
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Kumar Prabhash 
Designation  Professor and Head Solid Unit 
Affiliation  Tata Memorial centre 
Address  Room No 1108 11th Floor Department Of Medical Oncology, Homi Bhabha Block Tata Memorial Hospital E.Borges Road Parel Mumbai

Mumbai
MAHARASHTRA
400012
India 
Phone  02224177000  
Fax  02224171734  
Email  kprabhash1@gmail.com  
 
Details of Contact Person
Scientific Query  
Name  Dr Kumar Prabhash 
Designation  Professor and Head Solid Unit 
Affiliation  Tata Memorial centre 
Address  Room No 1108 11th Floor Department Of Medical Oncology, Homi Bhabha Block Tata Memorial Hospital E.Borges Road Parel Mumbai

Mumbai
MAHARASHTRA
400012
India 
Phone  02224177000  
Fax  02224171734  
Email  kprabhash1@gmail.com  
 
Details of Contact Person
Public Query  
Name  Dr Kumar Prabhash 
Designation  Professor and Head Solid Unit 
Affiliation  Tata Memorial centre 
Address  Room No 1108 11th Floor Department Of Medical Oncology, Homi Bhabha Block Tata Memorial Hospital E.Borges Road Parel Mumbai

Mumbai
MAHARASHTRA
400012
India 
Phone  02224177000  
Fax  02224171734  
Email  kprabhash1@gmail.com  
 
Source of Monetary or Material Support  
Tata Memorial Centre, Dr E Borges Road, Parel, Mumbai, 400012, India  
 
Primary Sponsor  
Name  Tata Memorial Centre 
Address  Dr E Borges Parel Mumbai 400012 
Type of Sponsor  Research institution and hospital 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
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 Gaurav Kumar  Homi Bhabha Cancer Hospital and Research Centre, Muzaffarpur  Department of Medical Oncology Room no 108 HBCHRC SKMCH Campus Uma Nagar Rasulpur Muzaffarpur 842004
Muzaffarpur
BIHAR 		 9264493969

gaurav.kumar@tmc.gov.in 
Dr Kumar Prabhash  Tata Memorial Centre  Room No 1108 11th Floor Department Of Medical Oncology, Homi Bhabha Block Tata Memorial Hospital E.Borges Road Parel Mumbai
Mumbai
MAHARASHTRA 		 9167760576
02224171734
kprabhash1@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 2  
Name of Committee  Approval Status 
Institutional Ethics committee  Approved 
Institutional Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: K229||Disease of esophagus, unspecified,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Physicians choice chemotherapy + Low dose Nivolumab 40mg 3weekly  Paclitaxel should be administered first. Paclitaxel 175 mg/m2 three weekly OR 80 mg/m2 weekly is administered in a 500mL sodium chloride 0.9% non-PVC infusion bag with a 0.22 micron in-line filter over 3 hours. Pre-medications will include intravenous dexamethasone 8mg, intravenous diphenhydramine 12.5mg, Tablet Famotidine 20mg per oral, and intravenous granisetron 1mg. Growth factors are not mandatory, but may be used if the treating physician thinks they are indicated. Cycles will be repeated every 3 weekly, continuously until progressive disease, excessive toxicity, as per physicians discretion or if patient withdraws consent. Following chemotherapy, the patient will be prescribed oral antiemetic agents on an as needed basis. Carboplatin will be administered at a dose of Area Under the Curve (AUC) 5 or 6 in 250ml of dextrose over 30mins. When given in a combination with Paclitaxel, the pre- and post-chemotherapy medications would be similar to that prescribed for Paclitaxel. Cycles will be repeated every 3 weekly, continuously until progressive disease, excessive toxicity, as per physicians discretion or if patient withdraws consent. Nivolumab 40 mg would be administered in 100 ml NS over 60 minutes every 3 weekly until progressive disease, excessive toxicity as per physicians discretion or if patient withdraws consent. 
Comparator Agent  Physicians choice chemotherapy alone   Paclitaxel should be administered first. Paclitaxel is administered175 mg/m2 three weekly OR 80 mg/m2 weekly in a 500mL sodium chloride 0.9% non-PVC infusion bag with a 0.22 micron in-line filter over 3 hours. Pre-medications will include intravenous dexamethasone 8mg, intravenous diphenhydramine 12.5mg, Tablet Famotidine 20mg per oral, and intravenous granisetron 1mg. Growth factors are not mandatory, but may be used if the treating physician thinks they are indicated. Cycles will be repeated every 3 weekly, continuously until progressive disease, excessive toxicity, as per physicians discretion or if patient withdraws consent. Following chemotherapy, the patient will be prescribed oral antiemetic agents on an as needed basis. Carboplatin will be administered at a dose of Area Under the Curve (AUC) 5 or 6 in 250ml of dextrose over 30mins. When given in a combination with Paclitaxel, the pre- and post-chemotherapy medications would be similar to that prescribed for Paclitaxel. Cycles will be repeated every 3 weekly, continuously until progressive disease, excessive toxicity, as per physicians discretion or if patient withdraws consent. 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  1 Subjects must have histologically proven squamous cell carcinoma of the oesophagus and must be planned for palliative intent systemic therapy
2 Subjects must be treatment naïve or if they have received systemic therapy in the curative setting it must be greater than or equal to 3 months prior.

3 Age Male or female or Transgender subjects aged greater than or equal to 18 years.

4 Eastern Cooperative Oncology Group ECOG performance status PS 0 to 2.

5 Subjects must have normal organ and marrow function as defined below
a Hematologic Absolute neutrophil count ANC greater than or equal to 1.0 multiplied by 109 per L platelet count greater than or equal to 100 multiplied by 109 per L and haemoglobin greater than or equal to 8 g per dL .
b Hepatic Total bilirubin level less than or equal to 1.5 multiplied by the upper limit of normal ULN range and AST and ALT levels less than or equal to 2.5 multiplied by ULN or AST and ALT levels less than or equal to 5 multiplied by ULN for subjects with documented metastatic disease to the liver.
c Renal Estimated creatinine clearance greater than or equal to 30 mL per min

6 Patients with HIV are potentially eligible as long as they have a CD4 count greater than 200 are on concurrent HAART highly active antiretroviral therapy and absence of active AIDS defining conditions.

7 Pregnancy test Negative serum or urine pregnancy test at screening for women of childbearing potential.

8 Contraception Highly effective contraception for both male and female subjects throughout the study and for at least 30 days after last Nivolumab treatment administration if the risk of conception exists. The effects of Nivolumab on the developing human foetus are teratogenic. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study she should inform her treating physician immediately.

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 Immunosuppressants Current use of immunosuppressive medication EXCEPT for the following a intranasal inhaled topical steroids or local steroid injection e g intraarticular injection b Systemic corticosteroids at physiologic doses less than or equal to 10 mg per day of prednisone or equivalent c Steroids as premedication for hypersensitivity reactions eg CT scan premedication d Steroids for raised intracranial pressure due to the disease itself eg Steroid use for avoidance or treatment of emesis.

3 Autoimmune disease Active autoimmune disease that might deteriorate when receiving a chemotherapeutic agent. Patients with diabetes type I vitiligo psoriasis or hypo or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.

4 Organ transplantation Prior organ transplantation including allogeneic stemcell transplantation.

5 Infections Active infection requiring systemic therapy.

6 Hepatitis Hepatitis B virus HBV or hepatitis C virus HCV 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 wont rule the patient out.

7 Vaccination Vaccination within 4 weeks of the first dose of Nivolumab and while on study is prohibited except for administration of inactivated vaccines.

8 Hypersensitivity to study drug Known prior severe hypersensitivity to investigational product or any component in its formulations.

9 Cardiovascular disease Clinically significant ie active cardiovascular disease unstable angina congestive heart failure greater than or equal to New York Heart Association Classification Class II or more or serious uncontrolled cardiac arrhythmia .

10 Other persisting toxicities Persisting toxicity related to prior therapy NCI CTCAE v4 03 Grade greater than or equal to 2 however alopecia sensory neuropathy Grade less than or equal to 2 or other Grade less than or equal to 2 not constituting a safety risk based on Investigators judgment is acceptable.

11 Other severe acute or chronic medical conditions including immune colitis inflammatory bowel disease immune pneumonitis chronic kidney disease chronic liver disease pulmonary fibrosis or psychiatric conditions including recent within the past year or active suicidal ideation or behaviour

12 Pregnant women are excluded from this study. Advise females of reproductive potential to use effective contraception during treatment and for at least one month after the last dose of Nivolumab.

13 Lactating females There is no information regarding the presence of Nivolumab in human milk the effects on the breastfed infant or the effects on milk production. Since many drugs are excreted in human milk it is advised that a lactating woman should not breastfeed during treatment and for at least one month after the last dose of Nivolumab due to the potential for serious adverse reactions in breastfed infants.
 
 
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  At Death  
 
Secondary Outcome  
Outcome  TimePoints 
Progression free Survival  Till disease progression 
Objective Response rate   Baseline , every 2-3 months till progression 
Toxicity  At every visit  
QOL  Baseline, every 2 months till disease progression 
Dysphagia free survival  Baseline and till first progression of dysphagia 
 
Target Sample Size   Total Sample Size="320"
Sample Size from India="320" 
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)   10/04/2024 
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="4"
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 if palliative chemotherapy with low dose Nivolumab prolongs overall survival as compared to palliative chemotherapy alone in patients with advanced unresectable or metastatic esophageal and gastroesophageal junction squamous cell cancer that is not amenable to curative intent therapy.

 Study Design

Phase III, Double arm, Open Label, Randomized Controlled Superiority 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.

Screening:

Patients will be screened post-consenting. Each referred patient will be assessed on the basis of study eligibility criteria for this study. Investigations mentioned under baseline assessment would be performed at the time of screening if necessary for eligibility assessment. We will maintain a confidential screening log of all potential study candidates that includes information of the subjects (e.g., name, medical record number, phone number), date of screening, and outcome of screening process (i.e., enrolled in the study, screen failure with the reason for ineligibility, refused to participate).

Study Population:Eligible patients with advanced unresectable or metastatic esophageal and gastroesophageal junction squamous cell cancer that is not amenable to curative intent therapy.

Treatment Plan: Eligible patients will be randomized in a 1:1 manner to physicians choice chemotherapy (Paclitaxel with Carboplatin, Single agent Paclitaxel or Docetaxel) versus physicians choice chemotherapy with Low dose Nivolumab 40mg every 3-weekly. Patients will be assessed with CT scans every 2-3 months until progressive disease or unacceptable treatment related toxicity. Following progression/discontinuation, patients will be followed up and treated as per the discretion of the treating physician. Patients will be followed every 2-3 months until death for survival analysis. 

Statistical Analysis

Baseline assumption

The median survival of patients with metastatic oesophageal squamous cell carcinoma treated with standard palliative chemotherapy is approximately 9 months. The addition of low dose Nivolumab is expected to increase the median OS from 9 months to 13 months.

Sample size

With 80% power and a 2-sided alpha of 0.05, we will need to recruit 289 patients, assuming that the patients will be recruited over 4 years and we have a minimum follow up of 12 months after the last patient has been recruited. We expect 10% lost to follow up which will make the sample size 320 for this study. 

 
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