Health Condition 1: C159- Malignant neoplasm of esophagus, unspecified
Conditions
Interventions
Intervention1: Arm B(Experimental Arm): Neoadjuvant chemotherapy ( FLOT regimen) + low-dose Nivolumab followed by surgery
Intervention2: Arm C(Experimental Arm): Neoadjuvant Chemoradiation (CROSS regi
Sponsors
NCG-ICMR
Indian Council of Medical Research
Eligibility
Inclusion criteria
Inclusion criteria: 1. Newly diagnosed Histologically proven squamous carcinoma of esophagus 2. No prior surgery (except endoscopic biopsy) or chemotherapy or radiation 3. Pre-treatment stage cT1N+ M0 or cT2-4a N0/N+, M0 (In case of stage cT4a, curative resectability has to be explicitly verified and documented by the local surgical investigator prior to randomization) 4. No invasion of the tracheobronchial tree or presence of tracheoesophageal fistula. 5. Sexually active patients of childbearing potential must implement effective contraceptive practices during the study when treated with chemotherapy. 6. Age greater than 18 years, willing to give written informed consent. 7. Eastern Cooperative Oncology Group (ECOG) performance status 0 2 8. Adequate cardiac function. Patients with a history of cardiac illness should have a cardiology consultation and should have a left ventricular ejection fraction greater than 50 % (determined by echocardiography) 9. Adequate bone marrow function (White Blood Cells greater than 3000/cumm; Hemoglobin greater than 8 g/dl; platelets greater than 100,000/cumm) 10. Adequate renal function (Calculated Glomerular filtration rate Cockroft Gault Formula greater than 60 ml/min) 11. Adequate liver function (Total bilirubin less than 3 g/dL, SGOT/SGPT less than 5X upper limit of normal, Albumin greater than 3g/dL)
Exclusion criteria
Exclusion criteria: 1. Patients with adenosquamous or adenocarcinoma histology 2. Cervical esophageal cancers 3. Inability to provide informed consent due to psychological, social, and other factors 4. Dementia or altered mental status that would prohibit the understanding and giving of informed consent 5. A history of malignancies other than esophageal cancer before enrolment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer; 6. Comorbidities which will not allow administration of chemotherapy, radiation or immunotherapy or will preclude esophagectomy CTC grade greater than 1 peripheral neuropathy; Poorly controlled diabetes mellitus ( HbA1C greater than 8) (These patients will be rescreened after the consultation with Physician and optimization of the oral hypoglycaemics and/or insulin) Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of Nivolumab , paclitaxel, and cisplatin; Preexisting or coexisting bleeding disorder New York Heart Association Class III/IV and history of active angina. Documented myocardial infarction within the 6 months preceding registration (pretreatment ECG evidence of infarct only will not exclude patients). Patients with a history of significant ventricular arrhythmia requiring medication or congestive heart failure. History of 2nd or 3rd degree heart blocks Liver dysfunction Child-Pugh B or C Active organ infections including pneumonia, pulmonary tuberculosis, pyelonephritis, HIV, active hepatitis B (HBV DNA greater than or equal to 2000 IU/mL or 104 copies/mL) and hepatitis C (positive for hepatitis C antibody and HCV RNA levels higher than the lower limit of the assay). American Society of Anaesthesiologist (ASA) score 3 or more Autoimmune disease History of organ transplantation or allogeneic bone marrow transplantation 7. For Female Participants Pregnancy Lactating women Women of child bearing potential (WOCBP) or their partners who are unwilling to practice contraception
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare Progression-free survival of the two experimental arms with the control armTimepoint: 3 months after surgery, once every 3 months for 3 years then 6 monthly till progression or death. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Overall survival between the study arms 2. Quality of life 3. Disease free survival 4. Pathological complete response rates 5. R0 resection rates 6. Grade 3 / grade 4 adverse events with different neoadjuvant therapy strategies 7. Postoperative complications 8. Treatment related mortality 9. 30-day mortality after surgery 10. Health resource utilization 11. Site of failure in patients who experience recurrence local, loco-regional, distant or combined 12. Treatment completion ratesTimepoint: Baseline, Pre-chemo, During Chemotherapy (Day 0, Day 14, Day 28, Day 42), Post-chemo, 3 months after surgery, once every 3 months for 3 years then 6 monthly till progression or death. | — |
Countries
India
Contacts
Public ContactDr C S Pramesh
Tata Memorial Hospital, Mumbai
Outcome results
None listed