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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Multicenter Randomized Phase III Trial of Neo-adjuvant Chemotherapy Followed by Surgery and Chemotherapy or by Surgery and Chemoradiotherapy in Resectable Gastric Cancer (CRITICS Study)

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: cisplatin+capecitabine
* Radiation: radiotherapy
* Drug: epirubicin+cisplatin+capecitabine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1chemoradiotherapy<br>5 weeksadjuvant treatment; radiotherapy and concomitant chemotherapy with cisplatin and capecitabine. | Drug: cisplatin+capecitabine<br>* cisplatin 20 mg/m2 (i.v., q 1 w, 5 weeks), capecitabine 575 mg/m2 (b.i.d., oral, on radiotherapy days.<br>Radiation: radiotherapy<br>* 45 Gy in 25 fracions (5 days/week)<br>|
| Active Comparator: 2chemotherapy<br>3 adjuvant courses epirubicin, cisplatin, capecitabine. | Drug: epirubicin+cisplatin+capecitabine<br>* 3 courses q 3 w: epirubicin 50 mg/m2 (i.v., day 1), cisplatin 60 mg/m2 (i.v., day 1), capecitabine 1000 mg/m2 (b.i.d., oral, day 1-14)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | study duration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease-free survival |  | study duration | 
| toxicity |  | study duration | 
| health-related quality of life |  | study duration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CRITICS, gastric cancer, surgery, adjuvant, chemotherapy, chemoradiotherapy, capecitabine, cisplatin, epirubicin