Efficacy and Safety Study of the Combined Modality Therapy in Adenocarcinoma of the Esophago-gastric Junction

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Medical University of Lublin
Sponsor:
Information provided by (Responsible Party):
Tomasz Skoczylas, Medical University of Lublin
ClinicalTrials.gov Identifier:
NCT01523015
First received: January 25, 2012
Last updated: February 2, 2013
Last verified: February 2013
  Purpose

The high cancer related mortality has remained a significant issue of health care in Poland, Europe and worldwide. The decreasing incidence rate for carcinoma of the distal stomach and a marked trend of increasing incidence for adenocarcinoma of the esophago-gastric junction and esophagus has been observed in the developed countries. The most eminent drawback of majority commonly cited randomized trials is heterogenicity of cancer patient population. The epidemiological, pathological, and clinical data clearly suggest that adenocarcinoma of the esophago-gastric junction is the entirety different both from adenocarcinoma of the esophagus and adenocarcinoma of the stomach. 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 carcinoma of the esophago-gastric junction. The proposed study has been designed to achieve the following objectives:

  • The assessment of safety and efficacy of a combined modality therapy in homogenous patient population with adenocarcinoma of the esophago-gastric junction excluding individuals with adenocarcinoma of the esophagus or the stomach;
  • The assessment of safety of a combined modality therapy in a form of chemo- and chemoradiotherapy related toxicity and impact of chemo- and chemoradiotherapy on postoperative morbidity or mortality rates;
  • The assessment of efficacy of a combined modality therapy in a form of rate of response of the tumor to chemo- and chemoradiotherapy and a curative resection rate.
  • The assessment of efficacy of a combined modality therapy in a form of cancer free survival and overall survival.

Condition Intervention Phase
Adenocarcinoma of the Gastroesophageal Junction
Other: preoperative chemo- and chemoradiotherapy
Procedure: Surgical resection
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Medical University of Lublin:

Primary Outcome Measures:
  • Pathological response to treatment [ Time Frame: 6-12 weeks after chemoradiotherapy ] [ Designated as safety issue: No ]
    Pathological response to treatment assessed as a tumor regresion grade in histopahological assessment of the surgical specimen


Secondary Outcome Measures:
  • Clinical response to treatment [ Time Frame: 5 weeks after chemoradiotherapy ] [ Designated as safety issue: No ]
    Clinical response to treatment based on the modified RECIST criteria measured by CT

  • The curative resection (R0) rate [ Time Frame: 6-12 weeks after chemoradiotherapy ] [ Designated as safety issue: No ]
    The curative resection (R0) rate defined by the assessment of proximal, distal and circumferential margins

  • chemoradiotherapy related toxicity [ Time Frame: 6-12 weeks after chemoradiotherapy ] [ Designated as safety issue: Yes ]
    The rate and intensity of chemo- and chemoradiotherapy related toxicity

  • postoperative complications rate [ Time Frame: 30 days after surgical resection ] [ Designated as safety issue: Yes ]
    The rate and intensity of postoperative morbidity and mortality

  • Overall and cancer free survival [ Time Frame: 5 years from onset of the chemoradiotherapy ] [ Designated as safety issue: No ]
    Overall and cancer free survival

  • Quality of life changes [ Time Frame: 5 years after the onset of cheemoradiotherapy ] [ Designated as safety issue: No ]
    Quality of life changes

  • The rate of chemo- and chemoradiotherapy dose reduction [ Time Frame: 11 weeks during chemo- and chemoradiotherapy ] [ Designated as safety issue: Yes ]
    The rate of dose reduction due to chemotherapy or radiotherapy related toxicity


Estimated Enrollment: 100
Study Start Date: January 2012
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combined therapy
The combined modality therapy will be consisted of preoperative chemoradiotherapy (Docetaxel, Oxaliplatin, 5-Fluorouracil, 45Gy) for type I i II cancer or preoperative chemotherapy (Docetaxel, Oxaliplatin, 5-Fluorouracil) for type III cancer and followed by surgery.
Other: preoperative chemo- and chemoradiotherapy
2 cycles of triple regimen chemotherapy consisting of docetaxel (75mg/m2 iv infusion), oxaliplatin (130mg/m2 iv infusion) and 5-fluorouracil (750mg/m2 iv infusion followed by fractionated irradiation (total dose 45Gy in 25 fractions of 1,8Gy) combined with chemotherapy consisting of 3 cycles of 1-day chemotherapy with docetaxel (50mg/m2 iv infusion) and oxaliplatin (85mg/m2 iv infusion
Other Names:
  • docetaxel,
  • oxaliplatin,
  • 5-fluorouracil,
  • irradiation
Active Comparator: Surgery
The extent of surgery will be associated with the topographic type of carcinoma of the esophagogastric junction: type I - subtotal esophagectomy with superior gastric resection, splenectomy and two-field mediastinal lymph node dissection; type II and III - total gastrectomy with distal esophagectomy, splenectomy and D2 with mediastinal inferior lymph node dissection.
Procedure: Surgical resection
The extent of surgery will be associated with the topographic type of carcinoma of the esophagogastric junction: type I - subtotal esophagectomy with superior gastric resection, splenectomy and two-field mediastinal lymph node dissection; type II and III - total gastrectomy with distal esophagectomy, splenectomy and D2 with mediastinal inferior lymph node dissection.
Other Names:
  • esophagectomy,
  • gastrectomy

Detailed Description:

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 modalities.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 cT2-4aN0-3M0.
  • 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
  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: NCT01523015

Contacts
Contact: Tomasz Skoczylas, MD, PhD +48 81 5328810 tomskocz@yahoo.com

Locations
Poland
Second Department of General & Gastrointestinal Surgery & Oncological Surgery of the Alimantary Tract, Medical University of Lublin Recruiting
Lublin, Lubelskie, Poland, 20-081
Contact: Tomasz Skoczylas, MD, PhD    +48 81 5328810    tomskocz@yahoo.com   
Principal Investigator: Tomasz Skoczylas, MD, PhD         
Principal Investigator: Grzegorz Wallner, Professor         
Principal Investigator: Andrzej Dąbrowski, Professor         
Sub-Investigator: Witold Zgodziński, MD, PhD         
Sub-Investigator: Marek Majewski, MD, PhD         
Sponsors and Collaborators
Medical University of Lublin
Investigators
Principal Investigator: Tomasz Skoczylas, MD, PhD Second Department of General & Gastrointestinal Surgery & Surgical Oncology of the Alimentary Tract, Medical University of Lublin
Principal Investigator: Grzegorz Wallner, Professor Second Department of General & Gastrointestinal Surgery & Surgical Oncology of the Alimentary Tract, Medical University of Lublin
Principal Investigator: Andrzej Dąbrowski, Professor Second Department of General & Gastrointestinal Surgery & Surgical Oncology of the Alimentary Tract, Medical University of Lublin
Principal Investigator: Witold Zgodziński, MD, PhD Second Department of General & Gastrointestinal Surgery & Surgical Oncology of the Alimentary Tract, Medical University of Lublin
Principal Investigator: Marek Majewski, MD, PhD Second Department of General & Gastrointestinal Surgery & Surgical Oncology of the Alimentary Tract, Medical University of Lublin
Principal Investigator: Maria Mazurkiewicz, Professor Department of Oncology, Medical University of Lublin, Lublin Oncology Center
Principal Investigator: Anna Brzozowska, MD, PhD Department of Oncology, Medical University of Lublin, Lublin Oncology Center
Principal Investigator: Ludmiła Grzybowska-Szatkowska, MD, PhD Department of Oncology, Medical University of Lublin, Lublin Oncology Center
Principal Investigator: Witold Krupski, Professor Second Department of Radiology, Medical University of Lublin
Principal Investigator: Ewa Kurys-Denis, MD, PhD Second Department of Radiology, Medical University of Lublin
Principal Investigator: Justyna Szumiło, Professor Department of Clinical Pathomorphology, Medical University of Lublin
Principal Investigator: Agnieszka Fronczek, MD Department of Clinical Pathomorphology, Medical University of Lublin
  More Information

No publications provided

Responsible Party: Tomasz Skoczylas, Principal Investigator, Medical University of Lublin
ClinicalTrials.gov Identifier: NCT01523015     History of Changes
Other Study ID Numbers: EGC-0254/87/2011, UML-EGC-2011
Study First Received: January 25, 2012
Last Updated: February 2, 2013
Health Authority: Poland: Ethics Committee

Keywords provided by Medical University of Lublin:
Adenocarcinoma
esophago-gastric cancer
chemotherapy
chemoradiotherapy
surgery

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Fluorouracil
Oxaliplatin
Docetaxel
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 23, 2014