Operable patients = 18 years of age with locoregionally advanced squamous cell- or adenocarcinoma of the esophagus or esophagogastric junction
Conditions
Interventions
Trade Name: Opdivo (100mg/10ml)
Product Name: Nivolumab
Product Code: BMS-936558
Pharmaceutical Form: Concentrate for solution for injection
Sponsors
Erasmus MC Cancer Institute
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria 1. Age =18; 2. Written informed consent and ability to understand the nature of the study and the study-related procedures and to comply with them 3. Histologically proven, resectable adenocarcinoma or squamous cell carcinoma of the esophagus or GEJ according to the UICC TNM7 definition. Tumors of the esophagus and tumors of which the epicentre is within 5 cm of the GEJ are eligible for inclusion in the trial (Type 1 and Type 2 according to Siewert classification of esophagogastric adenocarcinoma 4. Pre-treatment stage cT2-4aN0-3M0 disease. In case of stage cT4a, the possibility for a curative resection has to be explicitly verified by the multidisciplinary tumor board 5. nCRT (CROSS regimen) completed, i.e. all radiotherapy fractions administered. 6. Complete clinical response 10-14 weeks after nCRT as determined by endoscopy with biopsies, EUS with FNA and PET/CT scanning 7. No prior cytotoxic chemotherapy other than as part of the neoadjuvant chemoradiation (CROSS) 8. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 9. Adequate cardiac function (cardiac function tests such as echocardiography only necessary in symptomatic patients). 10. Adequate respiratory function (pulmonary function tests only necessary in symptomatic patients). 11. Adequate bone marrow function (White Blood Cells >2x10^9/l; Haemoglobin >6,2mmol/L; platelets >100x10^9/l). In the event of transfusions, the last red blood cell transfusion should be more than 2 weeks before inclusion. 12. Adequate renal function (Glomerular Filtration Rate >40 ml/min) or Serum creatinine =65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: Exclusion criteria 1. Language difficulty, dementia or altered mental status prohibiting the understanding and giving of informed consent and to complete quality of life questionnaires; 2. Patients who were treated with definitive chemoradiotherapy 3. Esophageal cancer evaluated as not curatively-resectable by the multidisciplinary tumour board, for instance because ingrowth in the trachea, aorta or vertebra (cT4b) 4. Gastric carcinoma 5. Clinically significant (active) cardiac disease (e.g. symptomatic coronary artery disease or myocardial infarction within last 12 months) 6 Pregnant and lactating women, or patients of reproductive potential who are not using effective birth control methods. If barrier contraceptives are used, they must be continued by both sexes throughout the study. 7 Participation, current or during the last 30 days prior to informed consent, in another intervention trial with interference to the chemotherapeutic or chemoradiotherapeutic intervention of this study. 8. Expected lack of compliance with the protocol 9. Refusal to undergo further active surveillance (i.e., opting for esophageal resection) 10. Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured or successfully resected, such as basal or squamous cell skin cancer, superficial bladder cancer, or GC, or carcinoma in situ of the prostate, cervix, or breast 11. Participants with an active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enrol. 12. Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents for adults, or > 0.25 mg/kg daily prednisone equivalent for adolescent) or other immunosuppressive medications within 14 days of study treatment. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents for adults, or > 0.25 mg/kg daily prednisone equivalent for adolescents are permitted, in the absence of active autoimmune disease. 13. Participants who received prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways 14. Anti-tumor treatment other than as part of neoadjuvant chemoradiation (CROSS) within 28 days of first administration of study treatment 15. Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). 16. Any positive test result for hepatitis B virus or hepatitis C virus indicating presence of virus, e.g, hepatitis B surface antigen (HBsAg, Australia antigen) positive, or hepatitis C antibody (anti-HCV) positive (except if HCV-RNA negative) 17. Participants must not have received a live / attenuated vaccine within 30 days of first treatment. 18. History of severe hypersensitivity reactions to other monoclonal antibodies 19. History of allergy or hypersensitivity to study drug components
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: ? To assess health-related quality of life ? To assess 2-year overall and distant metastases-free survival ? To assess toxicity during and after this treatment ? To assess the proportion of patients with curable disease that go on to need surgery ? To assess complications after nivolumab and surgery.;Primary end point(s): Primary endpoint is disease-free survival (DFS);Timepoint(s) of evaluation of this end point: defined as the time elapsed between inclusion and locoregional or distant disease recurrence or death, whichever comes first.;Main Objective: To assess the disease-free survival in patients treated with nivolumab during active surveillance in patients who have achieved cCR after nCRT for esophageal and gastroesophageal cancer | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - proportion of patients who develop locoregional disease recurrence - proportion of patients who develop distant metastases - proportion of patients that undergo esophageal surgery with curative intent - Overall survival (OS) calculated from the date of inclusion to death due to any cause. Patients still alive at last contact will be censored - Quality of life, as measured by quality of life questionnaires: EORTC QLQ-OG25 and EORTC-C30 - Surgical morbidity (Clavien-Dindo grade 3B or higher) and mortality (30-day and-or in hospital mortality). Complications will be monitored according to the Dutch Society for Surgery complication registry (DUCA) and Esophagectomy Complications Consensus Group ECCG - Serious adverse events and grade 3-4 adverse events from the time of their first treatment with nivolumab according to the Common Terminology Criteria for Adverse Events (CTCAE version 5.0);Timepoint(s) of evaluation of this end point: Follow up: at baseline, 3, 6, 12 and 24 months after inclusion, overall survival at 2 years | — |
Countries
Netherlands
Contacts
Public ContactJessie Huizer
Erasmus MC Cancer Institute
Outcome results
None listed