Esophageal squamous cell carcinoma
Conditions
Interventions
Product Name: bintrafusp alfa
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: BINTRAFUSP ALFA
Current Sponsor code: M7824
Concentration unit: mg milligram(s)
Concentrat
Sponsors
Amsterdam University Medical Centers
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically proven squamous cell carcinoma of the esophagus or gastro esophageal junction. - Surgically irresectable (T1-T4a, N0 or N+, M0), as determined by Endoscopic Ultra Sound (EUS), PET scan and diagnostic CT scan of neck, thorax and abdomen. Patients with M1 disease solely on the basis of supraclavicular metastasis are eligible. Patients with resectable tumors refusing radical surgery or inoperable patients due to comorbidity are eligible. - Locoregional recurrences without distant metastasis after surgery alone or endoscopical resection - Locoregional recurrences without distant metastasis after neoadjuvant chemoradiation + resection or definitive chemoradiation outside the previously irradiated area, provided that full dose of radiation can safely be delivered. - 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. - ECOG performance status 0-2 - Adequate hematological, renal and hepatic functions. - Written, voluntary informed consent - Patients must be accessible to management and follow-up in the treatment center Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 27
Exclusion criteria
Exclusion criteria: - Past or current history of malignancy other than entry diagnosis interfering with prognosis of esophageal cancer. - Patient with tracheo-esophageal fistula or extension into the mucosal layer of the trachea, highly at risk to develop fistula. Thus, tumor extension to the trachea is allowed, but not through the trachea. - Patient with aortal involvement with high risk of bleeding or developing a fistula. - Patients with pathological lymph nodes at both supraclavicular and truncus coeliacus level. - Pregnancy (positive serum pregnancy test), planning to become pregnant, and lactation. - Patient (male or female) in the reproductive age 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. - Previous chemotherapy, radiation and/or treatment with checkpoint inhibitors for the currently present esophageal tumor. - Previous chemotherapy and/or treatment with targeted agents and/or checkpoint inhibitors for other forms of cancer within the last six months. - Previous radiation to the mediastinum precluding full dose radiation of the currently present esophageal tumor. - Presence of an esophageal stent. - History of bleeding diathesis or major bleeding event (grade = 2) in the month prior to first dose of trial treatment. - Clinically significant cardiovascular disease precluding safe treatment with chemoradiation. - Evidence of pulmonary fibrosis and/or clinically significant impairment of lung function precluding safe treatment with chemoradiation. In case of doubt about pulmonary function, a lung function test should be performed and, in case of abnormalities, discussed with the principle investigator. - 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. - 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. - Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine for patients with a history of autoimmune-related hypothyroidism, insulin for patients with type 1 diabetes mellitus, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Patients with vitiligo with dermatological manifestations only are eligible to enter the study. - Diagnosis of HIV unless stable on antiretroviral therapy for at least 4 weeks, no evidence of multi-drug resistance, viral load of 10 mg/day prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. - Evidence of interstitial lung disease or active, non-infectious pneumonitis. - An active infection requiring systemic therapy, which has not resolved 3 days (simple infection such as cystitis) to 7 days (severe infection such a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to assess the feasibility of bintrafusp alfa combined with definitive chemoradiation (carboplatin, paclitaxel and radiation) in terms of completion of treatment with bintrafusp alfa of patients with squamous cell carcinoma of the esophagus or gastroesophageal junction. ;Secondary Objective: 1.Incidence and severity of toxicity defined according to CTCAE v5 and Radiation Oncology Group (RTOG) criteria. 2. Safety of bintrafusp alfa in combination with definitive chemoradiotherapy 3.Percentage completion of chemotherapy and radiation treatment 4.Percentage withdrawal rate from chemoradiation due to bintrafusp alfa related complications 5.Infield locoregional progression free survival 6.Any progression free survival 7.Overall survival 8.Quality of life, with a special focus on dysphagia 9.To perform exploratory biomarker analyses from tumor tissue and blood-derived samples and correlate with safety and clinical outcome. ;Primary end point(s): The primary endpoint is feasibility defined as percentage of patients that complets at least two of the three planned cylces of bintrafusp alfa. ;Timepoint(s) of evaluation of this end point: After last treatment cycle | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Incidence and severity of toxicity defined according to CTCAE v5 and Radiation Oncology Group (RTOG) criteria. 2. Safety of bintrafusp alfa in combination with definitive chemoradiotherapy 3. Percentage completion of chemotherapy and radiation treatment 4. Percentage withdrawal rate from chemoradiation due to bintrafusp alfa related complications 5. Infield locoregional progression free survival 6. Any progression free survival 7. Overall survival 8. Quality of life, with a special focus on dysphagia 9. Potential biomarker development based on assessment of tumour and duodenal biopsies, faeces and blood samples ;Timepoint(s) of evaluation of this end point: During treatment and one week after treatment. Follow up data will be collected following standard follow up visits. | — |
Countries
Netherlands
Contacts
Public ContactStudy Coordinator
Amsterdam University Medical Centers
Outcome results
None listed