Clinical trial NCT01271322: Sequential FDG-PET (Positron Emission Tomography) and Induction Chemotherapy in Locally Advanced Adenocarcinoma of the Esophagogastric Junction (AEG)
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
Overall status: TERMINATED
Phase: PHASE2
Conditions: 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
Lead sponsor: National Center for Tumor Diseases, Heidelberg
Sponsor class: OTHER
First posted: 2011-01-06
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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..

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.

Primary outcomes:
measure: Correlation between change in tumor metabolism (detected by PET) and histopathological response
timeFrame: PET Baseline, PET1 (before RCHT, week 5/6), histological examination of the resected tumor
Secondary outcomes:
measure: distribution of change in tumor metabolism during the treatment in histological responders and non-responders
timeFrame: PET Baseline, PET1 (week 5/6), histological examination of the resected tumor
measure: accuracy of the binary prediction rule reduction in the tumor metabolism >65% vs. <65% in histopathological responders vs. non-responders
timeFrame: Baseline, PET1 (week 5/6), histological examination of the resected tumor
measure: association between change in tumor metabolism before/after radiochemotherapy and histopathological response
timeFrame: PET1 (week 5/6), PET2 (before resection), histological examination of the resected tumor
measure: association between change in tumor metabolism between PET Baseline and PET1 and overall survival as well as disease-free survival
timeFrame: Baseline, PET1 (week 5/6), Follow Up (q3 months during the first post-operative year, q6 months during the 2nd/3rd postoperative year)
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: Nationales Centrum für Tumorerkrankungen
Study officials:
affiliation: Dep. Of Medical Oncoloy, National Center for Tumor Diseases
name: Sylvie Lorenzen, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.