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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT00407186

Recruitment Status : Active, not recruiting

First Posted : December 4, 2006

Last Update Posted : October 10, 2017

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborators:

The Netherlands Cancer Institute

Roche Pharma AG

Information provided by (Responsible Party):

Dutch Colorectal Cancer Group

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Gastric Cancer	Drug: cisplatin+capecitabine Radiation: radiotherapy Drug: epirubicin+cisplatin+capecitabine	Phase 3

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 Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	788 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	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)
Actual Study Start Date :	January 11, 2007
Estimated Primary Completion Date :	December 2018
Estimated Study Completion Date :	December 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Stomach Cancer

Drug Information available for: Cisplatin Epirubicin Capecitabine

Genetic and Rare Diseases Information Center resources: Stomach Cancer

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1chemoradiotherapy 5 weeksadjuvant treatment; radiotherapy and concomitant chemotherapy with cisplatin and capecitabine.	Drug: cisplatin+capecitabine cisplatin 20 mg/m2 (i.v., q 1 w, 5 weeks), capecitabine 575 mg/m2 (b.i.d., oral, on radiotherapy days. Radiation: radiotherapy 45 Gy in 25 fracions (5 days/week)
Active Comparator: 2chemotherapy 3 adjuvant courses epirubicin, cisplatin, capecitabine.	Drug: epirubicin+cisplatin+capecitabine 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)

Outcome Measures

Primary Outcome Measures :

overall survival [ Time Frame: study duration ]

Secondary Outcome Measures :

disease-free survival [ Time Frame: study duration ]
toxicity [ Time Frame: study duration ]
health-related quality of life [ Time Frame: study duration ]

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00407186

Locations

Layout table for location information

Netherlands
Nederlands Kanker Instituut/Antoni van Leeuwenhoek Ziekenhuis
Amsterdam, Netherlands, 1066 CX

Sponsors and Collaborators

Dutch Colorectal Cancer Group

The Netherlands Cancer Institute

Roche Pharma AG

Investigators

Layout table for investigator information

Principal Investigator:	Marcel Verheij, MD PhD	Nederlands Kanker Insituut/Antoni van Leeuwenhoek Ziekenhuis

More Information

Additional Information:

Dutch Colorectal Cancer Group This link exits the ClinicalTrials.gov site

Nederlands Kanker Instituut/Antoni van Leeuwenhoek Ziekenhuis (Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital) This link exits the ClinicalTrials.gov site

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Quaas A, Biesma HD, Wagner AD, Verheij M, van Berge Henegouwen MI, Schoemig-Markiefka B, Pamuk A, Zander T, Siemanowski J, Sikorska K, Egthuijsen JMP, Meershoek-Klein Kranenbarg EM, van de Velde CJH, Buettner R, Alakus H, Cats A, Ylstra B, van Laarhoven HWM, van Grieken NCT. Microsatellite instability and sex differences in resectable gastric cancer - A pooled analysis of three European cohorts. Eur J Cancer. 2022 Sep;173:95-104. doi: 10.1016/j.ejca.2022.06.025. Epub 2022 Jul 18.

Slagter AE, Vollebergh MA, Caspers IA, van Sandick JW, Sikorska K, Lind P, Nordsmark M, Putter H, Braak JPBM, Meershoek-Klein Kranenbarg E, van de Velde CJH, Jansen EPM, Cats A, van Laarhoven HWM, van Grieken NCT, Verheij M. Prognostic value of tumor markers and ctDNA in patients with resectable gastric cancer receiving perioperative treatment: results from the CRITICS trial. Gastric Cancer. 2022 Mar;25(2):401-410. doi: 10.1007/s10120-021-01258-6. Epub 2021 Oct 29.

de Steur WO, van Amelsfoort RM, Hartgrink HH, Putter H, Meershoek-Klein Kranenbarg E, van Grieken NCT, van Sandick JW, Claassen YHM, Braak JPBM, Jansen EPM, Sikorska K, van Tinteren H, Walraven I, Lind P, Nordsmark M, van Berge Henegouwen MI, van Laarhoven HWM, Cats A, Verheij M, van de Velde CJH; CRITICS investigators. Adjuvant chemotherapy is superior to chemoradiation after D2 surgery for gastric cancer in the per-protocol analysis of the randomized CRITICS trial. Ann Oncol. 2021 Mar;32(3):360-367. doi: 10.1016/j.annonc.2020.11.004. Epub 2020 Nov 20.

Slagter AE, Sikorska K, Grootscholten C, van Laarhoven HWM, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, van de Velde CJH, van Grieken NCT, van Sandick JW, Jansen EPM, Verheij M, Cats A. Venous thromboembolism during preoperative chemotherapy in the CRITICS gastric cancer trial. Cancer Med. 2020 Sep;9(18):6609-6616. doi: 10.1002/cam4.3118. Epub 2020 Jul 31.

Slagter AE, Tudela B, van Amelsfoort RM, Sikorska K, van Sandick JW, van de Velde CJH, van Grieken NCT, Lind P, Nordsmark M, Putter H, Hulshof MCCM, van Laarhoven HWM, Grootscholten C, Braak JPBM, Meershoek-Klein Kranenbarg E, Jansen EPM, Cats A, Verheij M. Older versus younger adults with gastric cancer receiving perioperative treatment: Results from the CRITICS trial. Eur J Cancer. 2020 May;130:146-154. doi: 10.1016/j.ejca.2020.02.008. Epub 2020 Mar 21.

Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. doi: 10.1016/S1470-2045(18)30132-3. Epub 2018 Apr 9.

Dikken JL, van Sandick JW, Maurits Swellengrebel HA, Lind PA, Putter H, Jansen EP, Boot H, van Grieken NC, van de Velde CJ, Verheij M, Cats A. Neo-adjuvant chemotherapy followed by surgery and chemotherapy or by surgery and chemoradiotherapy for patients with resectable gastric cancer (CRITICS). BMC Cancer. 2011 Aug 2;11:329. doi: 10.1186/1471-2407-11-329.

Jansen EPM, Boot H, Dubbelman R, Verheij M, Cats A. Postoperative chemoradiotherapy in gastric cancer--a phase I-II study of radiotherapy with dose escalation of weekly cisplatin and daily capecitabine chemotherapy. Ann Oncol. 2010 Mar;21(3):530-534. doi: 10.1093/annonc/mdp345. Epub 2009 Aug 18.

Layout table for additonal information

Responsible Party:	Dutch Colorectal Cancer Group
ClinicalTrials.gov Identifier:	NCT00407186
Other Study ID Numbers:	CRITICS
First Posted:	December 4, 2006 Key Record Dates
Last Update Posted:	October 10, 2017
Last Verified:	October 2017

Keywords provided by Dutch Colorectal Cancer Group:


CRITICS gastric cancer surgery adjuvant chemotherapy	chemoradiotherapy capecitabine cisplatin epirubicin

Additional relevant MeSH terms:

Layout table for MeSH terms

Stomach Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Stomach Diseases Cisplatin Capecitabine	Epirubicin Antineoplastic Agents Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antibiotics, Antineoplastic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors

To Top