Sequential FDG-PET (Positron Emission Tomography) and Induction Chemotherapy in Locally Advanced Adenocarcinoma of the Esophagogastric Junction (AEG)

Phase 2

Terminated

• Conditions: Adenocarcinomas of the Esophagogastric Junction

• Registration Number: NCT01271322
• Lead Sponsor: National Center for Tumor Diseases, Heidelberg

Brief Summary

Prospective, single-center, nonrandomized, explorative imaging study evaluating the value of PET as a predictor of histopathological response in metabolic non-responders Patients with resectable AEG (adenocarcinoma of the esophagogastric junction) type I and II (cT3/4 and/or cN+ and cM0)

Metabolic non-responders, showing a \<35% decrease of SUV (standardized uptake value) two weeks after the start of neoadjuvant chemotherapy are eligible for the study and are taken to intensified taxane-based RCT (radiochemotherapy) before surgery. 18FDG-PET scans will be performed before (=Baseline) and after 14 days of standard neoadjuvant therapy as well after the first cycle of Taxotere/Cisplatin chemotherapy (=PET1) and at the end of intensified radiochemotherapy (PET2).

Tracer uptake will be assessed semiquantitatively using standardized uptake values (SUV). The percentage difference Delta SUV=100(SUVBaseline-SUVPET1)/ SUVBaseline will be calculated and assessed as an early predictor of histopathological response. In a secondary analysis, the association between the difference SUVPET1 - SUVPET2 and histopathological response will be evaluated.

Detailed Description

The HICON trial is a prospective, single-center, nonrandomized, explorative imaging study evaluating the value of PET (Positron emission tomography) as a predictor of histopathological response in metabolic non-responders Patients with resectable AEG (adenocarcinoma of the esophagogastric junction) type I and II, staged cT3/4 and/or cN+ and cM0 by endoscopic ultrasound, spiral CT or MRI and FDG-PET are eligible. Tumors must be potentially R0 resectable and must have a sufficient FDG-baseline uptake. Only metabolic non-responders, showing a \<35% decrease of SUV (standardized uptake value) two weeks after the start of neoadjuvant chemotherapy are eligible for the study and are taken to intensified taxane-based RCT (chemoradiotherapy (45 Gy) before surgery. 18FDG-PET scans will be performed before (=Baseline) and after 14 days of standard neoadjuvant therapy as well after the first cycle of Taxotere/Cisplatin chemotherapy (=PET1) and at the end of intensified radiochemotherapy (PET2). Tracer uptake will be assessed semiquantitatively using standardized uptake values (SUV). The percentage difference Delta SUV=100(SUVBaseline-SUVPET1)/ SUVBaseline will be calculated and assessed as an early predictor of histopathological response. In a secondary analysis, the association between the difference SUVPET1 - SUVPET2 and histopathological response will be evaluated..

Study Timeline

• Study Start: 2010-10
• Study First Submitted: 2010-12-17
• Study First Submitted QC: 2011-01-05
• Study First Posted: 2011-01-06
• Primary Completion: 2012-12
• Study Completion: 2012-12
• Status Verified: 2013-04
• Last Update Submitted: 2013-04-10
• Last Update Posted: 2013-04-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Biopsy-proven adenocarcinoma of the distal oesophagus (AEG type I) or cardia (AEG type II) with or without metastases in local lymph nodes (tumor stage cT3/T4, cNX, and cM0 in the tumor-node-metastasis classification)
• Staging procedures include endoscopy, endoscopic ultrasound and computed tomography (CT) of the chest and abdomen.
• Eligible patients have to be fit for platin-containing chemotherapy
• Tumors must be potentially R0 resectable tumors during consecutive operation.
• Tumors must have demonstrated a minimal amount of FDG-uptake in the baseline PET-CT, defined as 18FDG-uptake in tumor at first examination > 1,35 x hepatic-SUV + 2 x standard-deviation of hepatic-SUV, and must be a metabolic non-responder under EOX, defined as a decrease of the SUVmax of <35% in a second PET on day 14 of chemotherapy.

Exclusion Criteria

• Eastern Cooperative Oncology Group score >1
• Previous or secondary malignancy
• Life expectancy of less than 3 months
• Uncontrolled bleeding from the tumor
• Tumor infiltration of the airways
• Pregnancy
• Uncontrolled diabetes
• Patients are also ineligible if they have undergone previous chemotherapy, radiotherapy, or endoscopic laser therapy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Correlation between change in tumor metabolism (detected by PET) and histopathological response	PET Baseline, PET1 (before RCHT, week 5/6), histological examination of the resected tumor	The primary objective of the study is to evaluate the change in metabolic response - as measured by the relative difference delta SUV=100(SUVBaseline-SUVPET1)/ SUVBaseline in 18F-FDG uptake after 1 cycle of intensified taxan-based chemotherapy (PET1) - relative to the 18F-FDG uptake at the baseline examination, as a predictor of histopathological response in metabolic non-responders (assessed by PET 14 days after the start of neoadjuvant therapy).

Secondary Outcome Measures

Name	Time	Method
distribution of change in tumor metabolism during the treatment in histological responders and non-responders	PET Baseline, PET1 (week 5/6), histological examination of the resected tumor	investigation of the distribution of change in tumor metabolism measured with PET Baseline and PET1(∆SUV = 100 (SUVBaseline - SUVPET1) / SUVBaseline) during the treatment in histological responders and non-responders according to the Becker Score (Histomorphology and grading of regression)
accuracy of the binary prediction rule reduction in the tumor metabolism >65% vs. <65% in histopathological responders vs. non-responders	Baseline, PET1 (week 5/6), histological examination of the resected tumor	accuracy of the binary prediction rule delta SUV \>65% vs. \<65% (reduction in the tumor metabolism \>65% vs. \<65 % between PET Baseline and PET1 in correlation with the histopathological regression accoring to the Becker Score
association between change in tumor metabolism before/after radiochemotherapy and histopathological response	PET1 (week 5/6), PET2 (before resection), histological examination of the resected tumor	association between tumor metabolism before/after radiochemotherapy (∆SUV = 100 (SUVPET1 - SUVPET2) / SUVPET1) and histopathological response according to the Becker Score (histomorphology and grading of regression)
association between change in tumor metabolism between PET Baseline and PET1 and overall survival as well as disease-free survival	Baseline, PET1 (week 5/6), Follow Up (q3 months during the first post-operative year, q6 months during the 2nd/3rd postoperative year)	association between change in tumor metabolism between PET Baseline and PET 1 (∆SUV = 100 (SUVBaseline - SUVPET1) / SUVBaseline)and overall survival as well as disease-free survival

Trial Locations

Locations (1)

Nationales Centrum für Tumorerkrankungen; 🇩🇪 Heidelberg, Germany