Health Condition 1: C220- Liver cell carcinoma
Conditions
Interventions
Intervention1: 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
Sponsors
Tata Memorial Hospital
Eligibility
Inclusion criteria
Inclusion criteria: 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.
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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.Timepoint: 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
| Measure | Time frame |
|---|---|
| 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 v5.0Timepoint: 60 months | — |
Countries
India
Contacts
Public ContactDr Anant Ramaswamy
Tata Memorial Hospital
Outcome results
None listed