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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Center for Tumor Diseases, Heidelberg
ClinicalTrials.gov Identifier:
NCT01271322
First received: December 17, 2010
Last updated: April 10, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Adenocarcinomas of the Esophagogastric Junction
Radiation: neoadjuvant radiochemotherapy in metabolic non responders
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Center for Tumor Diseases, Heidelberg:

Primary Outcome Measures:
  • Correlation between change in tumor metabolism (detected by PET) and histopathological response [ Time Frame: PET Baseline, PET1 (before RCHT, week 5/6), histological examination of the resected tumor ] [ Designated as safety issue: No ]
    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 [ Time Frame: PET Baseline, PET1 (week 5/6), histological examination of the resected tumor ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, PET1 (week 5/6), histological examination of the resected tumor ] [ Designated as safety issue: No ]
    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 [ Time Frame: PET1 (week 5/6), PET2 (before resection), histological examination of the resected tumor ] [ Designated as safety issue: No ]
    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 [ 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) ] [ Designated as safety issue: No ]
    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


Study Start Date: October 2010
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Radiation: neoadjuvant radiochemotherapy in metabolic non responders
    Metabolic non-responders, with a SUV decrease of less than 35%, discontinue induction chemotherapy and proceed to an intensified radiochemotherapy treatment
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..

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01271322

Locations
Germany
Nationales Centrum für Tumorerkrankungen
Heidelberg, Germany, 69120
Sponsors and Collaborators
National Center for Tumor Diseases, Heidelberg
Investigators
Principal Investigator: Sylvie Lorenzen, MD Dep. Of Medical Oncoloy, National Center for Tumor Diseases
  More Information

No publications provided by National Center for Tumor Diseases, Heidelberg

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Center for Tumor Diseases, Heidelberg
ClinicalTrials.gov Identifier: NCT01271322     History of Changes
Other Study ID Numbers: NCT200811021017
Study First Received: December 17, 2010
Last Updated: April 10, 2013
Health Authority: Germany: Federal Office for Radiation Protection

Keywords provided by National Center for Tumor Diseases, Heidelberg:
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

Additional relevant MeSH terms:
Adenocarcinoma
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases

ClinicalTrials.gov processed this record on September 18, 2014