NCT03087864

PDL-1 Targeting in Resectable Oesophageal Cancer

PDL-1 Targeting in Resectable Oesophageal Cancer: a Phase II Feasibility Study of Atezolizumab and Chemoradiation.

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (actual)
• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Objectives The primary objective of this study is to assess the feasibility of preoperative treatment with atezolizumab combined with preoperative chemoradiation (carboplatin, paclitaxel and radiation) in terms of completion of treatment with atezolizumab.

Detailed description

Objectives The primary objective of the study of this study is to assess the feasibility of preoperative treatment with atezolizumab combined with preoperative chemoradiation (carboplatin, paclitaxel and radiation) in terms of completion of treatment with atezolizumab. Secondary objectives are: * To assess toxicities of atezolizumab alone and in combination with chemoradiation. * To assess completion of chemotherapy and radiation treatment * To assess withdrawal rate from surgery * To assess post-operative complications. * To assess pathological response. * To assess R0 resection rate. * To assess the relation between gut microbiota composition and response. * To assess the relation between gut microbiota composition and toxicity. Explorative objectives are: To perform exploratory biomarker analyses from tumor tissue and blood-derived samples and correlate with safety and clinical outcome. Biomarker analyses include (but are not limited to): * Expression of PD-1, PD-L1 and FOXP3, presence of tumor infiltrating CD8+/CD4+ cytotoxic/helper T lymphocytes, IFNγ expression, presence of tumor macrophages, STAT3 and STAT6 expression, MHC classI, MHC class II, EBV and MSI status on tumor tissue. * RNA sequencing and whole exome sequencing to develop a predictive profile for response to treatment. * Analysis of ctDNA extracted from plasma of patients at four time points (baseline, directly after chemoradiation, at surgery and 3 months after surgery) and analyzed using Ion Torrent Next Generation sequence technology as a non-invasive marker for response to treatment. * Analysis of peripheral blood mononuclear cells (PBMCs) extracted from whole blood of patients at three time points ((baseline, directly after chemoradiation, at surgery) ) * Duodenal biopsy and morning faeces sample analysis as predictor of response will be done by HIT Chip flora mapping, an established sensitive RT-qPCR method which is developed for exact and sensitive enumeration of bacterial population.

Conditions

• Esophageal Cancer, Stage II
• Esophageal Cancer Stage III

Interventions

Type	Name	Description
DRUG	Atezolizumab	Atezolizumab 1200 mg i.v. day 1-22-43-64-85
DRUG	Carboplatin	Chemotherapy
DRUG	Paclitaxel	Chemotherapy
RADIATION	Radiotherapy 23 x 1.8 Gy	Radiotherapy

Timeline

• Start date: 2017-06-28
• Primary completion: 2019-07-01
• Completion: 2019-07-01
• First posted: 2017-03-23
• Last updated: 2020-05-11

Locations

1 site across 1 country: Netherlands