trastuzumab for HER2-positive esophageal adenocarcinoma

Inclusion criteria

• {"criterion_text":"- Histologically proven adenocarcinoma of the esophagus or gastroesophageal junction, T1N+M0; or T2-T4a N0 or N+ M0). - HER2-positive tumor defined as either IHC 3+ or IHC 2+, the latter in combination with ISH+, as assessed by the local laboratory on a primary tumor biopsy. HER2 status needs to be confirmed by the central laboratory, but does not affect start of treatment. - Surgical resectability, as determined during multidisciplinary meeting. Tumors that cannot be passed with an endoscope for endoscopic ultrasound are eligible if all other criteria are fulfilled. - If the tumor extends below the gastroesophageal (GE) junction into the proximal stomach, the bulk of the tumor must involve the esophagus or GE junction. - Age ≥ 18. - Patient is fit for esophagectomy.Adequate hematological, renal and hepatic functions defined as: o Neutrophils ≥ 1.5 x 109/L o Platelets ≥ 100 x 109/L o Hemoglobin ≥ 5.6 mmol o Total bilirubin ≤ 1.5 x upper normal limit o Creatinine < 150 μmol l-1 or creatinine clearance (Cockroft) ≥ 50 ml/min - Adequate left ventricular ejection fraction defined as an LVEF of ≥50% determined by transthoracic echocardiography or MUGA. - Written, voluntary informed consent - Patients must be accessible to follow up and management in the treatment center"}

Exclusion criteria

• {"criterion_text":"- T1N0 tumors or in situ carcinoma. - Past (within 5 years) or current history of malignancy other than entry diagnosis which has a worse expected prognosis than the current esophageal cancer. - Previous chemotherapy, radiotherapy, treatment with an anti-HER2 antibody or with small molecule HER2 inhibitors for esophageal cancer or for any other cancer within 6 months of diagnosis of esophageal cancer. - Previous radiation to the mediastinum precluding full dose radiation of the currently present esophageal tumor. - Invasion of the tracheobronchial tree or presence of tracheoesophageal fistula. - Pregnancy (positive serum pregnancy test), planning to become pregnant, and lactation. - Not willing to use highly effective methods of contraception (per institutional standard) during treatment (male or female) and for 6 months 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 (FEV1 < 1,5L) 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. - ECOG performance status 3 or higher (cf. Appendix A) - 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. - Evidence of interstitial lung disease or active, non-infectious pneumonitis. - 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. - Evidence of acute or chronic infection with hepatitis B, C or HIV. - History of prior allogeneic stem cell or solid organ transplantation. - Pre-existing motor or sensory neurotoxicity greater than or equal to CTC AE grade 2."}

Primary endpoints

• {"endpoint_text":"- overall survival","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- Quality-adjusted life years\n- Progression free survival\n- Pathological response according to the Mandard criteria\n- R0 resection rate\n- Safety in terms of:\n o Toxicity defined according to CTCAE v5.0 criteria.\n o Post-operative complications according to the Clavien - Dindo classification.\n- Percentage completion of chemotherapy and radiation treatment.\n- Quality of life","definition_or_measurement_approach":"Pathological response measured according to the Mandard criteria. Toxicity defined according to CTCAE v5.0. Post-operative complications assessed according to the Clavien-Dindo classification. Other endpoints (QALYs, PFS, R0 resection rate, completion rates, QoL) — measurement approaches not further specified in the CTIS record."}

Netherlands

Earliest CTIS Part Ii Submission Date

29-10-2024

Latest Decision Or Authorization Date

06-08-2025

Processing Time Days

281

Number Of Sites

31

Number Of Participants

408

Primary sponsor

Full Name

Amsterdam UMC Stichting

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands