Esophageal adenocarcinoma
Conditions
Interventions
tocilizumab
Sponsors
Investigator-initiated, sponsored by Oncode Institute
Eligibility
Inclusion criteria
Inclusion criteria: - Histologically proven adenocarcinoma of the esophagus or gastroesophageal junction. - Surgical resectability ( 60 ml/min - Written, voluntary informed consent - Patients must be accessible to follow up and management in the treatment center
Exclusion criteria
Exclusion criteria: - Past (within 5 years) or current history of malignancy other than entry diagnosis interfering with prognosis of esophageal cancer, not including superficial and adequately treated skin and cervical malignancies. - Previous chemotherapy, radiotherapy and/or treatment with IL-6 receptor blockers for esophageal cancer - Previous radiation to the mediastinum precluding full dose radiation of the currently present esophageal tumor. - Previous chemotherapy and/or treatment with targeted agents and/or IL-6 receptor blockers for other forms of cancer within the last six months. - Invasion of the tracheobronchial tree or presence of tracheoesophageal fistula. - T1N0 tumors or in situ carcinoma. - Pregnancy (positive serum pregnancy test), planning to become pregnant, and lactation. - Patient (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment. - Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) precluding major surgery. - Pulmonary fibrosis and/or severely impaired lung function precluding major surgery. - Serious underlying medical condition which would impair the ability of the patient to receive the planned treatment, including prior allergic reactions to drugs containing Cremophor, such as teniposide or cyclosporine. - Dementia or altered mental status that would prohibit the understanding and giving of informed consent - Inadequate caloric- and/or fluid intake despite consultation of a dietician and/or tube feeding. - Requires systemic treatment with IL6 receptor blockers or IL-6 antagonists, TNF-alpha blockers or other biologicals within the last six months before the first dose of trial treatment. - Has evidence of interstitial lung disease or active, non-infectious pneumonitis. - Has an active infection requiring systemic therapy which has not resolved 3 days (simple infection such as cystitis) to 7 days (severe infection such as pyelonephritis) prior to the first dose of trial treatment. - Has a total cholesterol > 6.5 mmol/L despite adequate treatment with lipid-lowering agents. - Has evidence of (latent) tuberculosis infection in patient history.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective of this study is to demonstrate that stroma-targeting by tocilizumab in esophageal adenocarcinoma patients with highly activated stroma increases efficacy of chemoradiotherapy measured by pathological response according to the Mandard criteria. Patients will be grouped for ADAM12, a non-invasive blood-borne marker of stromal activation. | — |
Secondary
| Measure | Time frame |
|---|---|
| ? Efficacy and mechanism of action of tocilizumab with neoadjuvant chemoradiation against esophagogastric cancer by: o R0 resection rate o Progression free survival o Overall survival o IL6-STAT3 pathway inhibition measured by gene expression analysis o Levels of IL-6 in serum. o Phosphorylated STAT3 and stromal abundance measured by immunohistochemistry in formalin-fixed paraffin-embedded tumor tissue ? Levels of ADAM12 in tumor biopsies and serum. ? Incidence and severity of toxicity defined according to CTCAE v5.0 and Radiation Oncology Group (RTOG) criteria. ? Incidence and severity of post-operative complications according to the Clavien - Dindo classification. ? Percentage completion of chemotherapy and radiation treatment. ? Percentage withdrawal rate from surgery due to tocilizumab related complications. ? Percentage delay of surgery due to tocilizumab related complications. | — |
Contacts
Public ContactBenthe Doeve
Amsterdam UMC
Outcome results
None listed