| CTRI Number |
CTRI/2025/02/079994 [Registered on: 06/02/2025] Trial Registered Prospectively |
| Last Modified On: |
11/03/2025 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug
Radiation Therapy |
| Study Design |
Non-randomized, Multiple Arm Trial |
|
Public Title of Study
|
mmunotherapy and Radiation in Operable Gastric Cancers |
Scientific Title of Study
Modification(s)
|
Phase 2 study evaluating the addition of immune-sensitizing radiotherapy and biomarker-driven low-dose nivolumab in locally advanced resectable gastroesophageal junction/gastric cancers |
| Trial Acronym |
NISaRGA |
|
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 Road Prabhadevi Department of Medical Oncology Tata Memorial Hospital Mumbai
Mumbai
MAHARASHTRA
400012
India |
| Phone |
9833034802 |
| 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 Road Prabhadevi Department of Medical Oncology Tata Memorial Hospital Mumbai
Mumbai
MAHARASHTRA
400012
India |
| Phone |
9833034802 |
| 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 Road Prabhadevi Department of Medical Oncology Tata Memorial Hospital Mumbai
Mumbai
MAHARASHTRA
400012
India |
| Phone |
9833034802 |
| Fax |
|
| Email |
anantr13@gmail.com |
|
|
Source of Monetary or Material Support
|
| Tata Memorial Hospital
Dr.Ernest Borges Road
Prabhadevi, Mumbai-400012
Maharashtra, India |
|
|
Primary Sponsor
|
| Name |
Tata Memorial Hospital |
| Address |
Tata Memorial Hospital Dr.Ernest Borges road Prabhadevi Mumbai 400012 |
| Type of Sponsor |
Research institution and hospital |
|
|
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 |
| Dr Anant Ramaswamy |
Tata Memorial Hospital |
Dr. Ernest borges Road
Prabhadevi Mumbai 400012
Mumbai
MAHARASHTRA |
9833034802
anantr13@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee I |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C220||Liver cell carcinoma, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Low-dose nivolumab and immune sensitizing radiotherapy |
Arm A CPS greater than equal to 10
Patients in Arm A will receive
1.A single dose of radiotherapy approximately 1 week prior to starting mFLOT chemotherapy plus Nivolumab
2.Injection Nivolumab 40mg Intravenously every 2 weeks with mFLOT chemotherapy
The combination of mFLOT and Nivolumab will be continued for 4 cycles following which there will be an assessment for surgery. Surgery will be considered approximately 2 to 6 weeks post 4th cycle of chemo immunotherapy
Arm B CPS greater than 5 and less than 10
Patients in Arm B will receive
1.Three doses of RT, 1st dose prior to starting mFLOT plus Nivolumab and then one dose each between Cycle 1 and Cycle 2 of mFLOT Nivolumab and Cycle 2 and Cycle 3 of mFLOT plus Nivolumab. Duration of treatment between Cycle 1 and Cycle 2 and Cycle 2 and Cycle 3 of therapy will be approximately 3 weeks, while duration of treatment between Cycle 3 and Cycle 4 of therapy will be 2 weeks as standard. |
| Comparator Agent |
Not Applicable |
Not Applicable |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
90.00 Year(s) |
| Gender |
Both |
| Details |
Histologically confirmed esophagogastric adenocarcinomas with the following features
Radiologically stage T2 or higher with nodal positivity cN plus or both and no clinical evidence of distant metastases.
No evidence of peritoneal disease including peritoneal cytology positivity or other sites of metastases on staging laparoscopy preferably.
No evidence of clinical or radiological gastric outlet obstruction including no findings on upper gastrointestinal endoscopy.
No evidence of acute bleeding tumor such as melena or hematemesis.
Age greater than 18 years.
ECOG performance status of 0 to 2.
The patient must be able to provide informed consent for the study.
The patient must not have any contraindications to receiving FLOT chemotherapy nivolumab or radiotherapy.
A combined positive score CPS of at least 5. The CPS is calculated using the following formula on biopsy specimens CPS equals the number of PDL1 stained cells tumor cells macrophages lymphocytes multiplied by 100 and then divided by the total number of viable tumor cells. Antibodies used will either be 28 8 on the Dako platform or SP263 on the Ventana platform.
The patient must be able to undergo radiation therapy as planned as detailed in the protocol.
Adequate hematological hepatic and renal end-organ function.
Normal cardiac ejection fraction and cardiac function as assessed by echocardiography and ECG.
Women of childbearing age must have a negative pregnancy test at the time of randomization and be willing to use adequate contraception during the treatment phase of the trial. |
|
| ExclusionCriteria |
| Details |
Squamous cell cancers of the oesophagus and stomach
Patients undergoing upfront resection for G or GEJ adenocarcinomas
Radiologically or endoscopically T1b or T2 N0 cancers
Known hypersensitivity or contraindications to docetaxel oxaliplatin, 5-FU or nivolumab
Contraindication to receive radiotherapy
Uncontrolled comorbidities or infections
Significant or uncontrolled autoimmune conditions precluding use of Nivolumab
Past or current history of other malignancies not curatively treated and without evidence of disease for more than 5 years except for curatively treated basal cell carcinoma of the skin and in situ carcinoma of the cervix
Baseline neuropathy greater than NCI Grade I
Subject is pregnant, breastfeeding, or planning to become pregnant within 6 months after the end of treatment
|
|
|
Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
| The primary outcome and endpoint of the study is assessment of pathological complete response PCR rates in surgical specimens post neoadjuvant chemotherapyimmunotherapy and immunesensitizing RT. Patients will be undergoing surgical resection after neoadjuvant therapy. Resection specimens graded as TRG1 at primary site and nodes will be considered as having pathological complete response PCR. The proportion of patients achieving PCR will be evaluated for measurement of primary endpoint of study. |
In Arm A The combination of mFLOT and Nivolumab will be given for 4 cycles following which there will be an assessment for surgery. Surgery will be considered approximately 2 to 6 weeks post 4th cycle of chemoimmunotherapy. In Arm B patient will receive Three doses of RT, 1st dose prior to starting mFLOT plus Nivolumab and then one dose each between Cycle 1 and Cycle 2 of mFLOT+Nivolumab and Cycle 2 and Cycle 3 of mFLOT plus Nivolumab. |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
Secondary endpoints
Progression free survival (PFS) will be defined as the time from randomization to the time of disease progression or lost to follow up whichever is earlier.
Overall survival (OS) will be defined as the time from randomization to the time of death, lost to follow up or last observation(whichever is earlier).
Response rates as per RECIST where feasible.
The side effects and adverse event profile with combination will be reported as NCI-CTCAE v5.0 |
60 months |
|
|
Target Sample Size
|
Total Sample Size="127"
Sample Size from India="127"
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 2 |
|
Date of First Enrollment (India)
|
05/02/2026 |
| 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="5"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Yet Recruiting |
| 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
|
A validated biomarker in G slash GEJ is a Combined positive score ie CPS. A large trial evaluating the addition of nivolumab to chemotherapy in
advanced G slash GEJ carcinomas suggested improvement in survival when a CPS cut-off
of greater than 5 was used, with even better outcomes when CPS greater than 10. We are using
similar cutoffs in the proposed study. Trials utilizing only ICIs with NACT
have shown an improvement in PCR rates. PCR is an accepted surrogate endpoint
in G slash GEJ cancers, and improving PCR can translate into improvements in
survival. The combination of low-dose ICIs (which has significant preclinical
rationale) with RT with standard chemotherapy in resectable G slash GEJ is novel with
biological rationale. The use of specialized immuno-sensitizing types of
radiotherapy with low-dose ICIs is cost-effective and takes advantage of the
synergistic activity between both. |