Health Condition 1: C159- Malignant neoplasm of esophagus, unspecified Health Condition 2: C155- Malignant neoplasm of lower thirdof esophagus Health Condition 3: C154- Malignant neoplasm of middle thirdof esophagus Health Condition 4: C158- Malignant neoplasm of overlappingsites of esophagus Health Condition 5: C153- Malignant neoplasm of upper thirdof esophagus
Conditions
Interventions
Intervention1: Docetaxel, Cisplatin/Carboplatin and 5-FU/Capecitabine: Patients will receive Docetaxel, Cisplatin/Carboplatin and 5-FU/Capecitabine.
5FU will be dosed at 750 mg/m2 continuous intraven
Sponsors
Tata Memorial Centre
Eligibility
Inclusion criteria
Inclusion criteria: Subjects must have histologically proven squamous cell carcinoma of the esophagus or esophagogastric junction. Tumor should be surgically resectable. Pre-treatment stage cT2-4a, N0-3, M0. Cervical esophageal cancers should be resectable without the need for laryngectomy. Male, female, or transgender subjects aged 18 to 75 years. Eastern Cooperative Oncology Group ECOG performance status 0 to 2. Subjects must have normal organ and marrow function as defined below: a. Hematologic: Absolute neutrophil count ANC greater than or equal to 1.0x109 per liter, platelet count greater than or equal to 100x109 per liter, and hemoglobin greater than or equal to 8 grams per deciliter. b. Hepatic: Total bilirubin level less than or equal to 1.5 times the upper limit of normal ULN range and AST and ALT levels less than or equal to 2.5 times ULN. c. Renal: Estimated creatinine clearance greater than or equal to 30 milliliters per minute. d. Pulmonary: Patients should have adequate pulmonary function tests. 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. Pregnancy test: Negative serum or urine pregnancy test at screening for women of childbearing potential. Women of childbearing potential must be willing to consent to using effective contraception such as hormonal contraceptives, bilateral tubal ligation, barrier with spermicide, intrauterine device while on treatment and for at least 3 months thereafter. A man who is the partner of a woman of childbearing potential must be willing to consent to using effective contraception such as vasectomy or barrier with spermicide while on treatment and for 3 months thereafter. Both men and women of all races and ethnic groups are eligible for this study. Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
Exclusion criteria: 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 Hepatitis B virus or hepatitis C virus infection at screening. Positive HBV surface antigen with 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 6 Hypersensitivity to study drug Known prior severe hypersensitivity to investigational product or any component in its formulations 7 Cardiovascular disease Clinically significant active cardiovascular disease unstable angina congestive heart failure Class 2 or more serious uncontrolled cardiac arrhythmia or asymptomatic individuals with ejection fraction below 50 percent 8 Other severe acute or chronic medical conditions including inflammatory bowel disease pneumonitis chronic kidney disease known peripheral neuropathy grade 1 or more chronic liver disease pulmonary fibrosis or psychiatric conditions including recent within the past year or active suicidal ideation or behavior 9 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 treatment completion 10 Any other malignancies within the last 5 years other than curatively treated basal cell carcinoma of the skin and in situ carcinoma of the cervix 11 Immunosuppressants Current use of immunosuppressive medication except for the following intranasal inhaled topical steroids or local steroid injection systemic corticosteroids at physiologic doses of 10 mg per day of prednisone or equivalent steroids as premedication for hypersensitivity reactions steroids for raised intracranial pressure due to the disease itself 12 Autoimmune disease Active autoimmune disease that might deteriorate when receiving a chemotherapeutic agent. Patients with diabetes type 1 vitiligo psoriasis or hypo or hyperthyroid diseases not requiring immunosuppressive treatment are eligible 13 Organ transplantation Prior organ transplantation including allogeneic stem cell transplantation 14 Vaccination Vaccination within 4 weeks of the first dose of Nivolumab and while on study is prohibited except for administration of inactivated vaccines 15 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 3-year event-free survival (EFS) ratesTimepoint: EFS will be measured from randomization to progression treatment discontinuation or death. It will be evaluated at 1, 2, 3, 4, and 5 years Outcome assessments for both arms: baseline Cycle 2 Day 1 of neoadjuvant chemotherapy (+/-15 days) first follow-up post-chemotherapy (+/-15 days) first follow-up post-surgery (+/-15 days), and at 2 and 4 months post-surgery (+/-15 days) | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival OS Objective Response Rates ORR Toxicity assessment Quality of life QOL assessment R0 Resection rates Peri and post operative complication rates Pathological response rates Tumour regression grades Patterns of treatment failure local vs loco regional vs distant Factors that impact OS Age Gender ECOG PS baseline body weight baseline haemoglobin baseline albumin histopathological grade Axial Imaging or Endoscopy defined location of the primary in the esophagus presence or absence of dysphagia pre operative T stage T2 vs T3 4 and N stage N0 1 vs N2 3 Neoadjuvant chemotherapy regimen used treatment completion rates response to neoadjuvant therapy underwent surgery versus not receipt of adjuvant immunotherapy versus not Factors that impact EFS Same as factors affecting OSTimepoint: Overall Survival OS Measured from the date of randomization until death from any cause. It will be described as median OS and as survival rates at 1 2 3 4 and 5 years post randomization Objective Response Rates ORR Calculated as the percentage of patients achieving a complete or partial response based on RECIST version 1.1 assessed after completion of neoadjuvant therapy Toxicity Assessment Acute Toxicity Assessed from the day of randomization until 90 days after the start of chemoradiotherapy CRT Chronic Toxicity Evaluated for events occurring beyond 90 days from the start of CRT Quality of Life QOL Assessment Conducted using EORTC QLQ C30 and QLQ OES18 questionnaires at Baseline Cycle 2 Day 1 of neoadjuvant therapy 15 days First follow up post treatment 15 days First follow up post surgery 15 days 2 months post surgery 15 days 4 months post surgery 15 days R0 Resection Rates Assessed at the time of surgery. Resection is considered R0 if no tumor cells are found within 1 mm of any resection margin Peri and Post Operative Complication Rates Evaluated at 30 days and 90 days post surgery using the Clavien Dindo classification Pathological Respons | — |
Countries
India
Contacts
Public ContactDr Nandini Menon
Tata Memorial Centre
Outcome results
None listed