Multicentric Randomised Trial for Resectable Gastric Cancer

Study Overview
=================
Brief Summary
-----------------
The CRITICS-II trial aims to identify the optimal preoperative regimen in resectable gastric cancer by comparing three investigational treatment arms: chemotherapy vs. chemotherapy and subsequent chemoradiotherapy vs. chemoradiotherapy. The rationale behind this trial design is based on the following concepts: Preoperative treatment is associated with better patient compliance than postoperative regimens Preoperative treatment increases the likelihood of disease downsizing/downstaging and radical R0 resections Preoperative paclitaxel/carboplatin-based concurrent chemoradiotherapy and DOC chemotherapy are effective, feasible and safe regimens

Official Title
-----------------
A Multicentre Randomised Phase II Trial of Neo-adjuvant Chemotherapy Followed by Surgery vs. Neo-adjuvant Chemotherapy and Subsequent Chemoradiotherapy Followed by Surgery vs. Neo-adjuvant Chemoradiotherapy Followed by Surgery in Resectable Gastric Cancer

Conditions
-----------------
Gastric Cancer

Intervention / Treatment
-----------------
* Drug: Docetaxel
* Drug: Oxaliplatin
* Drug: Capecitabine
* Procedure: gastrectomy
* Radiation: radiotherapy of gastric cancer
* Drug: Paclitaxel
* Drug: Carboplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: TNM 8th ed stage IB-IIIC gastric cancer (histologically proven); tumour bulk has to be in the stomach but may involve gastro-oesophageal junction WHO < 2 Age ≥ 18 yrs Resectable adenocarcinoma of the stomach or gastro-oesophageal junction No prior abdominal radiotherapy Haematology: Hb ≥5.0 mmol/l; leukocytes≥3.0x109/l, neutrophils ≥1.5x109/l, thrombocytes ≥100x109/l Renal function: serum creatinine ≤1.25x ULN, creatinine clearance ≥ 50 ml/min (calculated by Cockcroft and Gault formula) Liver function: total bilirubin ≤1.5x ULN, alkaline phosphatase and ASAT/ALAT ≤ 3x ULN At staging laparoscopy (mandatory) obtained biopsies of suspected peritoneal lesions and/or substantial free peritoneal fluid if any should be pathologically proven tumor negative Written informed consent Expected adequacy of follow-up Caloric intake≥1500 kcal/day, verified by a dietician before registration. if caloric intake is < 1500 kcal/day or if bodyweight has decreased > 10% over the last 6 months or > 5% over the last month, dietary intervention such as oral nutritional support or enteral tube feeding is mandatory Exclusion Criteria: T1N0 disease (assessed by 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; in case of a previous other malignancy with a disease-free period≥5 years, inclusion can be accepted after consultation of the principal investigator 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 concomitant diseases preventing the safe administration of study drugs or likely to interfere with study assessments Uncontrolled angina pectoris, cardiac failure or clinically significant arrhythmias Continuous use of immunosuppressive agents equivalent to >10 mg daily prednison Concurrent use of the antiviral agent sorivudine or chemically related analogues, such as brivudine Neurotoxicity > CTC grade 1 Pregnancy or breast feeding Patients (M/F) with reproductive potential not implementing adequate contraceptive measures Gastric or gastro-esophageal stent within radiation field

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: neo-adjuvant chemotherapy followed by surgery<br>4 courses of 3 weekly DOC followed by surgery | Drug: Docetaxel<br>* 3 weekly course of docetaxel i.v in arm 1 and 2<br>* Other names: Taxotere;Drug: Oxaliplatin<br>* 3 weekly course oxaliplatin as a 2 hr i.v. in arm 1 and 2<br>* Other names: Eloxatin;Drug: Capecitabine<br>* oral capecitabine in arm 1 and 2<br>* Other names: Xeloda;Procedure: gastrectomy<br>* resection of gastric cancer after pre-operative chemotherapy for all arms<br>|
| Active Comparator: neo-adjuvant chemo and subsequent CRT followed by surgery<br>2 courses of 3 weekly DOC and subsequent CRT followed by surgery | Drug: Docetaxel<br>* 3 weekly course of docetaxel i.v in arm 1 and 2<br>* Other names: Taxotere;Drug: Oxaliplatin<br>* 3 weekly course oxaliplatin as a 2 hr i.v. in arm 1 and 2<br>* Other names: Eloxatin;Drug: Capecitabine<br>* oral capecitabine in arm 1 and 2<br>* Other names: Xeloda;Procedure: gastrectomy<br>* resection of gastric cancer after pre-operative chemotherapy for all arms<br>Radiation: radiotherapy of gastric cancer<br>* 5 weeks of radiation, 5 times a week with a total of 45 Gy (in arm 2 and 3)<br>Drug: Paclitaxel<br>* 5 weeks of paclitaxel i.v once a week (in arm 2 and 3)<br>Drug: Carboplatin<br>* 5 weeks of carboplatin i.v once a week (in arm 2 and 3)<br>|
| Active Comparator: neo-adjuvant chemoradiotherapy followed by surgery<br>chemoradiotherapy followed by surgery | Procedure: gastrectomy<br>* resection of gastric cancer after pre-operative chemotherapy for all arms<br>Radiation: radiotherapy of gastric cancer<br>* 5 weeks of radiation, 5 times a week with a total of 45 Gy (in arm 2 and 3)<br>Drug: Paclitaxel<br>* 5 weeks of paclitaxel i.v once a week (in arm 2 and 3)<br>Drug: Carboplatin<br>* 5 weeks of carboplatin i.v once a week (in arm 2 and 3)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-Free survival | Event-free survival will be measured by clinical outcome and CT-scan | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Event (events: local recurrence, regional recurrence, local-regional recurrence or progression, distant recurrence, or death from any cause) | Interval between randomization and event measured by clinical outcome and CT scan | 1 year | 
| Time to recurrence (events: local recurrence, regional recurrence, local-regional recurrence or progression, distant recurrence) | Interval between randomization and recurrence determined by clinical outcome and CT scan | 1 year | 
| Toxicity | Number of patients with treatment-related adverse events as assessed by CTCAE v4.0 | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
gastric cancer, radiotherapy, chemoradiotherapy