CRITICS-II: Multicentric Randomised Trial for Resectable Gastric Cancer

Sponsor

The Netherlands Cancer Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT02931890

Collaborator

(none)

207

Enrollment

Locations

Arms

134.3

Anticipated Duration (Months)

7.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Gastric Cancer	Drug: Docetaxel Drug: Oxaliplatin Drug: Capecitabine Procedure: gastrectomy Radiation: radiotherapy of gastric cancer Drug: Paclitaxel Drug: Carboplatin	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

207 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 21, 2017

Anticipated Primary Completion Date :

Mar 1, 2024

Anticipated Study Completion Date :

Mar 1, 2029

Arms and Interventions

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

Arm

Intervention/Treatment

Active Comparator: neo-adjuvant chemotherapy followed by surgery

4 courses of 3 weekly DOC followed by surgery

Drug: Docetaxel

3 weekly course of docetaxel i.v in arm 1 and 2

Other Names:

Taxotere

Drug: Oxaliplatin

3 weekly course oxaliplatin as a 2 hr i.v. in arm 1 and 2

Other Names:

Eloxatin

Drug: Capecitabine

oral capecitabine in arm 1 and 2

Other Names:

Xeloda

Procedure: gastrectomy

resection of gastric cancer after pre-operative chemotherapy for all arms

Active Comparator: neo-adjuvant chemo and subsequent CRT followed by surgery

2 courses of 3 weekly DOC and subsequent CRT followed by surgery

Drug: Docetaxel

3 weekly course of docetaxel i.v in arm 1 and 2

Other Names:

Taxotere

Drug: Oxaliplatin

3 weekly course oxaliplatin as a 2 hr i.v. in arm 1 and 2

Other Names:

Eloxatin

Drug: Capecitabine

oral capecitabine in arm 1 and 2

Other Names:

Xeloda

Procedure: gastrectomy

resection of gastric cancer after pre-operative chemotherapy for all arms

Radiation: radiotherapy of gastric cancer

5 weeks of radiation, 5 times a week with a total of 45 Gy (in arm 2 and 3)

Drug: Paclitaxel

5 weeks of paclitaxel i.v once a week (in arm 2 and 3)

Drug: Carboplatin

5 weeks of carboplatin i.v once a week (in arm 2 and 3)

Active Comparator: neo-adjuvant chemoradiotherapy followed by surgery

chemoradiotherapy followed by surgery

Procedure: gastrectomy

resection of gastric cancer after pre-operative chemotherapy for all arms

Radiation: radiotherapy of gastric cancer

5 weeks of radiation, 5 times a week with a total of 45 Gy (in arm 2 and 3)

Drug: Paclitaxel

5 weeks of paclitaxel i.v once a week (in arm 2 and 3)

Drug: Carboplatin

5 weeks of carboplatin i.v once a week (in arm 2 and 3)

Outcome Measures

Primary Outcome Measures

Event-Free survival [1 year]
Event-free survival will be measured by clinical outcome and CT-scan

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medisch Centrum Leeuwarden	Leeuwarden	Friesland	Netherlands	8901BR
2	Radiotherapeutisch Instituut Friesland	Leeuwarden	Friesland	Netherlands	8934AD
3	Gelre Ziekenhuizen	Apeldoorn	Gelderland	Netherlands	7334DZ
4	Gelre Ziekenhuizen	Zutphen	Gelderland	Netherlands	7207AE
5	Zuyderland Medisch Centrum	Sittard-Geleen	Limburg	Netherlands	6162 BG
6	Viecuri Medisch Centrum	Venlo	Limburg	Netherlands	5912 BL
7	Elkerliek	Deurne	Noord Brabant	Netherlands	5751 CB
8	Catharina Ziekenhuis	Eindhoven	Noord Brabant	Netherlands	5602 ZA
9	Maxima Medisch Centrum	Eindhoven	Noord Brabant	Netherlands	5631 BM
10	St. Anna Zorggroep	Geldrop	Noord Brabant	Netherlands	5664 EH
11	Elkerliek	Helmond	Noord Brabant	Netherlands	5707 HA
12	Instituut Verbeeten	Tilburg	Noord Brabant	Netherlands	5022 GC
13	Bernhoven	Uden	Noord Brabant	Netherlands	5406 PT
14	Maxima Medisch Centrum	Veldhoven	Noord Brabant	Netherlands	5504 DB
15	Spaarne Gasthuis	Hoofddorp	Noord-Holland	Netherlands	2000 AK
16	Ziekenhuisgroep Twente	Almelo	Overijssel	Netherlands	7609 PP
17	Deventer Ziekenhuis	Deventer	Overijssel	Netherlands	7416 SE
18	Medisch Spectrum Twente	Enschede	Overijssel	Netherlands	7512 KZ
19	Leids Universitair Medisch Centrum	Leiden	Zuid Holland	Netherlands	2333 ZA
20	Reinier de Graaf Gasthuis	Delft	Zuid-Holland	Netherlands	2625 AD
21	Jeroen Bosch Ziekenhuis	's-Hertogenbosch		Netherlands	5223 GZ
22	Netherlands Cancer Instituut	Amsterdam		Netherlands	1066CX
23	Academisch Medisch Centrum	Amsterdam		Netherlands	1105AZ
24	HAGA ziekenhuis	Den Haag		Netherlands	2545AA
25	Universitair Medisch Centrum Groningen	Groningen		Netherlands	9713 GZ
26	Ziekenhuis St Antonius	Nieuwegein		Netherlands	3435CM
27	Elisabeth Tweesteden Ziekenhuis	Tilburg		Netherlands	5022GC
28	Universitair Medisch Centrum Utrecht	Utrecht		Netherlands	3508 GA