A phase II trial to evaluate safety and efficacy of adding durvalumab (MEDI4736) to standard neoadjuvant radiochemotherapy and of adjuvant durvalumab +/- tremelimumab in locally advanced esophageal adenocarcinoma and to evaluate biomarkers predictive for response to immune checkpoint inhibitio

Phase 1

• Conditions: locally advanced esophageal adenocarcinoma; MedDRA version: 20.0Level: LLTClassification code 10001173Term: Adenocarcinoma of esophagusSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-003048-22-DE
• Lead Sponsor: niversität zu Köln

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-04-01
• Last Update Posted: 22 June 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 56

Inclusion Criteria

written informed consent
- Histologically confirmed, resectable adenocarcinoma of the esophagus (uT2, uN+, cM0 or uT3, cNx, cM0)
- No preceding cytotoxic or targeted therapy
- No prior partial or complete tumour resection
- Male or female patients = 18 years of age at time of study entry
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
- Study participants must be willing to undergo at least 2 biopsies (baseline, after neoadjuvant treatment)
- Life expectancy of = 12 months
- Body weight > 30kg
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 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 41

Exclusion Criteria

- Study participants with squamous cell carcinoma of the oesophagus
- Prior treatment with chemotherapy, targeted therapy or radiotherapy for treatment of advanced disease
- Patients are excluded if they are not resectable because of tumor infiltrating any other organs (cM1), except the stomach, with risk for R1 or R2 resection or if they are not resectable in case of other serious or uncontrolled medical disease.
- Patients with tumour stadium less than uT3 or confirmed metastatic diseases
- Any other serious or uncontrolled medical disorder, active infections, physical exam findings, laboratory finding, altered mental status, or psychiatric condition that, in the opinion of the investigator, would limit a study participant’s ability to comply with the study requirements, substantially increase risk to the study participant, or impact the interpretability or study results
- Presence or history of any other primary malignancy other than adenocarcinoma of the esophagus within 5 years prior to enrolment into the trial, except for adequately treated basal or squamous cell carcinoma of the skin or any adequately treated in situ carcinoma
- Pregnant or breastfeeding females
- Patients has known current symptomatic congestive heart failure (NYHA III and IV), unstable angina pectoris, or cardiac arrhythmia

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: - To evaluate efficacy and safety of the IMP and to evaluate biomarkers predictive for response to immune checkpoint inhibition;Secondary Objective: - To determine the Best Objective Response (BOR)<br><br>- To determine PFS, DFS and OS in durvalumab vs. durvalumab + tremelimumab adjuvant treatment<br><br>- Esophageal cancer related Quality of Life (FACT-E)<br>;Primary end point(s): To assess the rate of complete pathological response. When durvalumab is added to CROSS (carboplatin/paclitaxel + 41,4Gy RTx) in the neoadjuvant setting and PFS in the adjuvant therapy/maintenance with durvalumab after surgery.<br><br>The primary endpoint for safety is incidence, severity and grading of treatment emergent AEs and SAEs<br>;Timepoint(s) of evaluation of this end point: Direct after surgery

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Response to neoadjuvant treatment (CR, PR, SD, PD) as defined by RECIST 1.1. and iRECIST criteria<br>2. PFS and OS in durvalumab vs. durvalumab+tremelimumab adjuvant treatment<br>3. Oesophageal cancer related Quality of Life (FACT-E);Timepoint(s) of evaluation of this end point: 1. Weeks 10 to 11, that means one to three weeks before surgery<br>2. Until disease progression (PFS) and/or until 12 months after last administering IMP <br>3. From screening until visit 20