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Efficacy and Safety Study of the Combined Modality Therapy in Patients With Potentially Resectable, Locally Advanced Adenocarcinoma of the Esophago-gastric Junction With Preoperative Chemo- and Chemoradiation Followed by Surgical Resection

Phase 2/Phase 3
18 Years
Open (Enrolling)
Adenocarcinoma of the Gastroesophageal Junction

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Trial Information

Efficacy and Safety Study of the Combined Modality Therapy in Patients With Potentially Resectable, Locally Advanced Adenocarcinoma of the Esophago-gastric Junction With Preoperative Chemo- and Chemoradiation Followed by Surgical Resection

Adenocarcinoma of the esophago-gastric junction (AEG) represents an aggressive disease with
poor prognosis. Surgery is the traditional mainstay of treatment for patients presenting
with locally advanced disease, defined as transmural invasion with or without lymph node
involvement. Surgical approach may differ, but the principal is to achieve wide mural
clearance, negative margins, and perform an adequate lymphadenectomy. Although surgery is
the primary modality that can cure patients, the majority of patients reveal recurrence
leading to death within 2 years after resection. The incidence of locoregional relapse in
most series and in phase II and phase III trials ranges from 25% to 60%, and 20-30% of these
patients have no evidence of distant metastases. Median survival with surgery alone for
localized disease remains poor, and ranges from 13 to 19 months with 5-year survival rates
at best approximately 40%. To improve a long-term outcome in patients with esophageal and
gastric cancers a combined modality therapy concept has been investigating for many years.
The experience in a combined modality therapy for adenocarcinoma of the esophago-gastric
junction have been extrapolated from studies on esophageal or gastric cancer, where the
investigated population involved in part patients with AEG.

The most eminent drawback of majority commonly cited randomized trials is heterogenicity of
cancer patients population. Most of them overlap between esophageal adenocarcinoma and
squamous cell carcinoma or between adenocarcinoma of the esophagus, esophagogastric junction
and the stomach. When the investigators reviewed the composition of the most prominent 10
studies population including 3171 patients with easophageal and gastric cancer the
investigators identified 911 (28.7%) patients with AEG. The remaining pooled population
involved 1173 (36.9%) patients with adenocarcinoma of the esophagus, 598 (18.9%) patients
with squamous cell carcinoma of the esophagus and 775 (24.4%) patients with adenocarcinoma
of the stomach. Only 1 randomized controlled trial concerned exclusively patients with AEG.
In this study preoperative chemoradiotherapy resulted in a 16% increase of 3-year survival.
Although its superiority was not proven (p=0.07), these data provide evidence that
preoperative chemoradiotherapy may improve survival and should be further investigated.
Interestingly, the survival benefit was evident although the postoperative mortality was
more than doubled (10.2% versus 3.8%) by adding chemotherapy. Although this study did not
meet its accrual goals and could not provide statistical significance, the improvement in
both local cancer free and overall survival suggest that preoperative chemoradiotherapy
appears most valuable modality treatment to cure patients with localized AEG. As it is more
than evident that major response to preoperative treatment is an important prognostic factor
future trials should aim to optimize preoperative treatment by combining all treatment

All above mentioned discrepancies regarding the optimal treatment for AEG brought the
investigators to an idea to design a study testing safety and efficacy of three-phase
combined modality therapy accommodating induction taxane-based triple chemotherapy followed
by concurrent chemoradiotherapy with 45Gy as a total dose of irradiation and subsequent
surgical resection in homogenous population of patients with clearly defined AEG. Taking
into account the results from recent phase II and III trials the proposed combined modality
regimen suggests substantial response to the neoadjuvant therapy and promising highly
effective loco-regional cancer clearance with moderate and acceptable tolerance despite a
complex and extensive treatment.

Inclusion Criteria:

- patients of both gender, aged more than 18, with histopathologically confirmed
adenocarcinoma of the esophagogastric junction

- medically fit to undergo a major surgery with planned thoracotomy and in general
condition allowing to tolerate chemo- or chemoradiotherapy (Karnofsky Performance
Status ≥70, ECOG 0-1).

- Carcinoma of the esophagogastric junction defined as adenocarcinoma involving
esophagogastric junction when its epicenter is localized within 5cm proximally or 5cm
distally to the anatomical esophagogastric junction with subclassification to 3
topographic types (type I between 5cm and 1cm above; type II between 1cm above and
2cm below; type III between 2cm and 5cm below anatomic junction of the esophagus and
the stomach).

- Potentially resectable, local or locoregional cancer with clinical staging

- The intended number of randomized patients has been set as 100: 50 patients
randomized to each therapeutic arm with assumption, that 80% of randomized patients
will complete the treatment protocol.

Exclusion Criteria:

- disseminated cancer

- poor general condition (KI <70)

- adenocarcinoma of the stomach

- adenocarcinoma of the esophagus

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Pathological response to treatment

Outcome Description:

Pathological response to treatment assessed as a tumor regresion grade in histopahological assessment of the surgical specimen

Outcome Time Frame:

6-12 weeks after chemoradiotherapy

Safety Issue:


Principal Investigator

Tomasz Skoczylas, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Second Department of General & Gastrointestinal Surgery & Surgical Oncology of the Alimentary Tract, Medical University of Lublin


Poland: Ethics Committee

Study ID:




Start Date:

January 2012

Completion Date:

December 2020

Related Keywords:

  • Adenocarcinoma of the Gastroesophageal Junction
  • Adenocarcinoma
  • esophago-gastric cancer
  • chemotherapy
  • chemoradiotherapy
  • surgery
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous