TOCILIZUMAB for Esophageal adenocarcinoma | Esophageal cancer

Inclusion criteria

• {"criterion_text":"- Histologically proven adenocarcinoma of the esophagus or gastroesophageal junction or high grade dysplasia with high clinical suspicion for adenocarcinoma which will be treated accordingly.\n- Surgical resectability ( 60 ml/min.\n- If a female patient is of child-bearing potential, as evidenced by regular menstrual periods, she must have a negative pregnancy test (urine or serum; beta-human chorionic gonadotropin (β-hCG)) documented prior to the first administration of study drug. If sexually active, the patient must agree to use contraception considered adequate and appropriate by the Investigator during the period of administration of study drug and after the end of treatment as recommended.\n- Written, voluntary informed consent.\n- Patients must be accessible to follow up and management in the treatment center."}

Exclusion criteria

• {"criterion_text":"- 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.\n- Previous chemotherapy, radiotherapy and/or treatment with IL-6 receptor blockers for esophageal cancer.\n- Previous radiation to the mediastinum precluding full dose radiation of the currently present esophageal tumor.\n- Previous chemotherapy and/or treatment with targeted agents and/or IL-6 receptor blockers for other forms of cancer within the last six months.\n- Invasion of the tracheobronchial tree or presence of tracheoesophageal fistula.\n- T1N0 tumors or in situ carcinoma.\n- Pregnancy (positive serum pregnancy test), planning to become pregnant, and lactation.\n- 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.\n- Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) precluding major surgery.\n- Pulmonary fibrosis and/or severely impaired lung function precluding major surgery.\n- 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.\n- Dementia or altered mental status that would prohibit the understanding and giving of informed consent.\n- Inadequate caloric- and/or fluid intake despite consultation of a dietician and/or tube feeding.\n- 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.\n- Has evidence of interstitial lung disease or active, non-infectious pneumonitis.\n- 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.\n- Has a total cholesterol > 6.5 mmol/L despite adequate treatment with lipid-lowering agents.\n- Has evidence of (latent) tuberculosis infection in patient history.\n- Receiving a live or live weakened vaccine during treatment with tocilizumab.\n- Has evidence of acute or chronic infection with hepatitis B.\n- Patients with prior allogeneic stem cell or solid organ transplantation.\n- Pre-existing motor or sensory neurotoxicity greater than WHO grade 1.\n- Known allergy for tocilizumab or one of its excipients (sucrose, polysorbate 80, disodium phosphate dodecahydrate, sodium dihydrogen phosphate dehydrate)."}

Primary endpoints

• {"endpoint_text":"- The primary endpoint is pathological response to chemoradiotherapy according to the Mandard criteria.","definition_or_measurement_approach":"Pathological response to chemoradiotherapy assessed according to the Mandard criteria."}

Secondary endpoints

• {"endpoint_text":"- R0 resection rate.\n- Progression free survival\n- Overall survival\n- IL-6-STAT3 pathway inhibition based on gene expression analysis\n- pSTAT3 and stromal abundance in formalin-fixed paraffin-embedded tumor tissue\n- Levels of IL-6 in serum.\n- Levels of ADAM12 in tumor biopsies and serum in relation to pathological response according to the Mandard criteria.\n- Incidence and severity of toxicity defined according to CTCAE v5.0 and Radiation Oncology Group (RTOG) criteria.\n- Incidence and severity of post-operative complications according to the Dindo classification.\n- Percentage completion of chemotherapy and radiation treatment\n- Percentage withdrawal rate from surgery due to tocilizumab related complications\n- Percentage delay of surgery due to tocilizumab related complications","definition_or_measurement_approach":"R0 resection rate assessed by surgical/pathology reports; Progression free survival and Overall survival assessed by standard clinical follow-up; IL-6-STAT3 pathway inhibition assessed by gene expression analysis; pSTAT3 and stromal abundance assessed by immunohistochemistry on formalin-fixed paraffin-embedded tumor tissue; Levels of IL-6 in serum measured by serum assays; Levels of ADAM12 in tumor biopsies and serum measured and correlated with pathological response (Mandard criteria); Incidence and severity of toxicity defined and graded according to CTCAE v5.0 and RTOG criteria; Post-operative complications assessed according to the Dindo (Clavien-Dindo) classification; Percentages of completion, withdrawal rate from surgery, and delays of surgery calculated from treatment and surgical records."}

Netherlands

Earliest CTIS Part Ii Submission Date

29-03-2024

Latest Decision Or Authorization Date

08-04-2024

Processing Time Days

10

Number Of Sites

1

Number Of Participants

3

Primary sponsor

Full Name

Amsterdam UMC

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands