Clinical trial NCT00407186: Randomized Phase III Trial of Adjuvant Chemotherapy or Chemoradiotherapy in Resectable Gastric Cancer (CRITICS)
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Gastric Cancer
Keywords: CRITICS
gastric cancer
surgery
adjuvant
chemotherapy
chemoradiotherapy
capecitabine
cisplatin
epirubicin
Lead sponsor: Dutch Colorectal Cancer Group
Sponsor class: OTHER
Collaborators: name: The Netherlands Cancer Institute
name: Roche Pharma AG
First posted: 2006-12-04
Enrollment: 788
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: overall survival
timeFrame: study duration
Secondary outcomes:
measure: disease-free survival
timeFrame: study duration
measure: toxicity
timeFrame: study duration
measure: health-related quality of life
timeFrame: study duration
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Nederlands Kanker Instituut/Antoni van Leeuwenhoek Ziekenhuis
Study officials:
affiliation: Nederlands Kanker Insituut/Antoni van Leeuwenhoek Ziekenhuis
name: Marcel Verheij, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.