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

Primary Purpose

Adenocarcinomas of the Esophagogastric Junction

Status
Terminated
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
neoadjuvant radiochemotherapy in metabolic non responders
Sponsored by
National Center for Tumor Diseases, Heidelberg
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adenocarcinomas of the Esophagogastric Junction focused on measuring PET, response evaluation, neoadjuvant, radiochemotherapy, adenocarcinoma of the esophagogastric junction, esophageal carcinoma, evaluation of preoperative (radio)-chemotherapy in patients with adenocarcinomas of the oesophagogastric junction

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Nationales Centrum für Tumorerkrankungen

Outcomes

Primary Outcome Measures

Correlation between change in tumor metabolism (detected by PET) and histopathological response
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

distribution of change in tumor metabolism during the treatment in histological responders and non-responders
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
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
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
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

Full Information

First Posted
December 17, 2010
Last Updated
April 10, 2013
Sponsor
National Center for Tumor Diseases, Heidelberg
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1. Study Identification

Unique Protocol Identification Number
NCT01271322
Brief Title
Sequential FDG-PET (Positron Emission Tomography) and Induction Chemotherapy in Locally Advanced Adenocarcinoma of the Esophagogastric Junction (AEG)
Acronym
HICON
Official Title
Sequential FDG-PET (Positron Emission Tomography) and Induction Chemotherapy in Locally Advanced Adenocarcinoma of the Esophagogastric Junction (AEG): The Heidelberg Imaging Program in Cancer of the Oesophago-gastric Junction During Neoadjuvant Treatment: HICON Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2013
Overall Recruitment Status
Terminated
Study Start Date
October 2010 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Center for Tumor Diseases, Heidelberg

4. Oversight

Data Monitoring Committee
No

5. Study Description

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..

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adenocarcinomas of the Esophagogastric Junction
Keywords
PET, response evaluation, neoadjuvant, radiochemotherapy, adenocarcinoma of the esophagogastric junction, esophageal carcinoma, evaluation of preoperative (radio)-chemotherapy in patients with adenocarcinomas of the oesophagogastric junction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A

8. Arms, Groups, and Interventions

Intervention Type
Radiation
Intervention Name(s)
neoadjuvant radiochemotherapy in metabolic non responders
Intervention Description
Metabolic non-responders, with a SUV decrease of less than 35%, discontinue induction chemotherapy and proceed to an intensified radiochemotherapy treatment
Primary Outcome Measure Information:
Title
Correlation between change in tumor metabolism (detected by PET) and histopathological response
Description
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).
Time Frame
PET Baseline, PET1 (before RCHT, week 5/6), histological examination of the resected tumor
Secondary Outcome Measure Information:
Title
distribution of change in tumor metabolism during the treatment in histological responders and non-responders
Description
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)
Time Frame
PET Baseline, PET1 (week 5/6), histological examination of the resected tumor
Title
accuracy of the binary prediction rule reduction in the tumor metabolism >65% vs. <65% in histopathological responders vs. non-responders
Description
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
Time Frame
Baseline, PET1 (week 5/6), histological examination of the resected tumor
Title
association between change in tumor metabolism before/after radiochemotherapy and histopathological response
Description
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)
Time Frame
PET1 (week 5/6), PET2 (before resection), histological examination of the resected tumor
Title
association between change in tumor metabolism between PET Baseline and PET1 and overall survival as well as disease-free survival
Description
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
Time Frame
Baseline, PET1 (week 5/6), Follow Up (q3 months during the first post-operative year, q6 months during the 2nd/3rd postoperative year)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sylvie Lorenzen, MD
Organizational Affiliation
Dep. Of Medical Oncoloy, National Center for Tumor Diseases
Official's Role
Principal Investigator
Facility Information:
Facility Name
Nationales Centrum für Tumorerkrankungen
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
21702914
Citation
Lorenzen S, von Gall C, Stange A, Haag GM, Weitz J, Haberkorn U, Lordick F, Weichert W, Abel U, Debus J, Jager D, Munter MW. Sequential FDG-PET and induction chemotherapy in locally advanced adenocarcinoma of the Oesophago-gastric junction (AEG): the Heidelberg Imaging program in Cancer of the oesophago-gastric junction during Neoadjuvant treatment: HICON trial. BMC Cancer. 2011 Jun 24;11:266. doi: 10.1186/1471-2407-11-266.
Results Reference
derived

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

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