Randomized Phase III Trial of Adjuvant Chemotherapy or Chemoradiotherapy in Resectable Gastric Cancer (CRITICS)

Phase 3

Active, not recruiting

• Conditions: Gastric Cancer
• Interventions: Drug: cisplatin+capecitabine; Drug: epirubicin+cisplatin+capecitabine; Radiation: radiotherapy

• Registration Number: NCT00407186
• Lead Sponsor: Dutch Colorectal Cancer Group

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of combined chemotherapy and radiotherapy (in comparison to chemotherapy alone) as adjuvant treatment after surgery for gastric cancer. Prior to surgery all patients will receive neo-adjuvant chemotherapy as well.

Detailed Description

The mainstay of curative treatment of gastric cancer is radical surgical dissection. Because most patients in the Western world present with advanced stages long term survival is found in about 25%, with local recurrences as part of treatment failure in up to 80% of cases. Studies examining the role of more extended lymph node dissections (D1 vs. D2), adjuvant radiotherapy or adjuvant chemotherapy did not result in a clinical relevant improvement of survival. In 2001 results of a South West Oncology group (SWOG) trial that randomized between surgery and surgery with chemoradiotherapy were published. This trial, that was hampered by suboptimal surgery (less than D1 in majority of patients) and radiotherapy (2D radiotherapy; 35% protocol deviations) showed an absolute increase in median survival of 9 months. More recently results of the MAGIC study, which randomized between surgery and surgery plus 6 perioperative courses of ECF chemotherapy, were presented. This regimen resulted in an absolute 5-year survival benefit of 13% and in a 10% higher resectability rate.

This phase III prospectively randomized study investigates whether chemoradiotherapy (45 Gy in 5 weeks with daily cisplatin and capecitabine) after preoperative chemotherapy (3x ECC (epirubicin, cisplatin, capecitabine)) and adequate (D1+) surgery leads to improved survival in comparison with postoperative chemotherapy (3x ECC). Furthermore, toxicity of both treatment regimens will be explored.

Study Timeline

• Study First Submitted: 2006-12-01
• Study First Submitted QC: 2006-12-01
• Study First Posted: 2006-12-04
• Study Start: 2007-01-11
• Status Verified: 2017-10
• Last Update Submitted: 2017-10-09
• Last Update Posted: 2017-10-10
• Primary Completion: 2018-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 788

Inclusion Criteria

• Ib-IVa (no distant metastases) gastric cancer (histologically proven); tumor bulk in the stomach
• WHO < 2
• Age ≥18 yrs
• Operable gastric cancer
• No prior abdominal radiotherapy or chemotherapy
• Tumornegative laparoscopy when CT suggests peritoneal carcinomatosis
• Start treatment within 10 working days after registration
• Written informed consent

Exclusion Criteria

• T1N0 disease (endoscopic ultrasound)
• Distant metastases
• Inoperable patients; due to technical surgery-related factors or general condition
• Previous malignancy, except adequately treated non-melanoma skin cancer or in-situ cancer of the cervix uteri.
• Solitary functioning kidney that will be within the radiation field
• Major surgery within 4 weeks prior to study treatment start, or lack of complete recovery from the effects of major surgery
• Uncontrolled (bacterial) infections
• Significant cardiac disorders
• Continuous use of immunosuppressive agents
• Concurrent use of the antiviral agent sorivudine or chemically related analogues
• Hearing loss > CTC grade 1
• Neurotoxicity > CTC grade 1

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1chemoradiotherapy	cisplatin+capecitabine	5 weeksadjuvant treatment; radiotherapy and concomitant chemotherapy with cisplatin and capecitabine.
1chemoradiotherapy	radiotherapy	5 weeksadjuvant treatment; radiotherapy and concomitant chemotherapy with cisplatin and capecitabine.
2chemotherapy	epirubicin+cisplatin+capecitabine	3 adjuvant courses epirubicin, cisplatin, capecitabine.

Primary Outcome Measures

Name	Time	Method
overall survival	study duration

Secondary Outcome Measures

Name	Time	Method
disease-free survival	study duration
toxicity	study duration
health-related quality of life	study duration

Trial Locations

Locations (1)

Nederlands Kanker Instituut/Antoni van Leeuwenhoek Ziekenhuis; 🇳🇱 Amsterdam, Netherlands