Multicentric Randomised Trial for Resectable Gastric Cancer (CRITICS-II)

April 30, 2024 updated by: The Netherlands Cancer Institute

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

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

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

207

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • 's-Hertogenbosch, Netherlands, 5223 GZ
        • Jeroen Bosch Ziekenhuis
      • Amsterdam, Netherlands, 1105AZ
        • Academisch Medisch Centrum
      • Amsterdam, Netherlands, 1066CX
        • Netherlands Cancer Instituut
      • Arnhem, Netherlands, 6815AD
        • Rijnstate
      • Den Haag, Netherlands, 2545AA
        • Haga Ziekenhuis
      • Ede, Netherlands, 6716RP
        • Ziekenhuis Gelderse Vallei
      • Groningen, Netherlands, 9713 GZ
        • Universitair Medisch Centrum Groningen
      • Nieuwegein, Netherlands, 3435CM
        • Ziekenhuis St Antonius
      • Tilburg, Netherlands, 5022GC
        • Elisabeth Tweesteden Ziekenhuis
      • Utrecht, Netherlands, 3508 GA
        • Universitair Medisch Centrum Utrecht
    • Friesland
      • Leeuwarden, Friesland, Netherlands, 8901BR
        • Medisch Centrum Leeuwarden
      • Leeuwarden, Friesland, Netherlands, 8934AD
        • Radiotherapeutisch Instituut Friesland
    • Limburg
      • Sittard-Geleen, Limburg, Netherlands, 6162 BG
        • Zuyderland Medisch Centrum
      • Venlo, Limburg, Netherlands, 5912 BL
        • VieCuri Medisch Centrum
    • Noord Brabant
      • Deurne, Noord Brabant, Netherlands, 5751 CB
        • Elkerliek
      • Eindhoven, Noord Brabant, Netherlands, 5602 ZA
        • Catharina Ziekenhuis
      • Eindhoven, Noord Brabant, Netherlands, 5631 BM
        • Maxima Medisch Centrum
      • Geldrop, Noord Brabant, Netherlands, 5664 EH
        • St. Anna Zorggroep
      • Helmond, Noord Brabant, Netherlands, 5707 HA
        • Elkerliek
      • Tilburg, Noord Brabant, Netherlands, 5022 GC
        • Instituut Verbeeten
      • Uden, Noord Brabant, Netherlands, 5406 PT
        • Bernhoven
      • Veldhoven, Noord Brabant, Netherlands, 5504 DB
        • Maxima Medisch Centrum
    • Noord-Holland
      • Hoofddorp, Noord-Holland, Netherlands, 2000 AK
        • Spaarne Gasthuis
    • Overijssel
      • Almelo, Overijssel, Netherlands, 7609 PP
        • Ziekenhuisgroep Twente
      • Deventer, Overijssel, Netherlands, 7416 SE
        • Deventer Ziekenhuis
      • Enschede, Overijssel, Netherlands, 7512 KZ
        • Medisch Spectrum Twente
    • Zuid Holland
      • Leiden, Zuid Holland, Netherlands, 2333 ZA
        • Leids Universitair Medisch Centrum
    • Zuid-Holland
      • Delft, Zuid-Holland, Netherlands, 2625 AD
        • Reinier de Graaf Gasthuis

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-Free survival
Time Frame: 1 year
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)
Time Frame: 1 year
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)
Time Frame: 1 year
Interval between randomization and recurrence determined by clinical outcome and CT scan
1 year
Toxicity
Time Frame: 1 year
Number of patients with treatment-related adverse events as assessed by CTCAE v4.0
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Netherlands Cancer Institute

Investigators

  • Principal Investigator: Marcel Verheij, MD, PhD, The Netherlands Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 21, 2017

Primary Completion (Estimated)

April 1, 2025

Study Completion (Estimated)

March 1, 2029

Study Registration Dates

First Submitted

September 14, 2016

First Submitted That Met QC Criteria

October 11, 2016

First Posted (Estimated)

October 13, 2016

Study Record Updates

Last Update Posted (Actual)

May 2, 2024

Last Update Submitted That Met QC Criteria

April 30, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M15CRI
  • NL 55436.031.015 (Registry Identifier: CCMO)
  • 2015-004627-31 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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