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Open Access 01-12-2018 | Study protocol

CRITICS-II: a multicentre randomised phase II trial of neo-adjuvant chemotherapy followed by surgery versus neo-adjuvant chemotherapy and subsequent chemoradiotherapy followed by surgery versus neo-adjuvant chemoradiotherapy followed by surgery in resectable gastric cancer

Authors: Astrid E. Slagter, Edwin P. M. Jansen, Hanneke W. M. van Laarhoven, Johanna W. van Sandick, Nicole C. T. van Grieken, Karolina Sikorska, Annemieke Cats, Pietje Muller-Timmermans, Maarten C. C. M. Hulshof, Henk Boot, Maartje Los, Laurens V. Beerepoot, Frank P. J. Peters, Geke A. P. Hospers, Boudewijn van Etten, Henk H. Hartgrink, Mark I. van Berge Henegouwen, Grard A. P. Nieuwenhuijzen, Richard van Hillegersberg, Donald L. van der Peet, Heike I. Grabsch, Marcel Verheij

Published in: BMC Cancer | Issue 1/2018

Abstract

Background

Although radical surgery remains the cornerstone of cure in resectable gastric cancer, survival remains poor. Current evidence-based (neo)adjuvant strategies have shown to improve outcome, including perioperative chemotherapy, postoperative chemoradiotherapy and postoperative chemotherapy. However, these regimens suffer from poor patient compliance, particularly in the postoperative phase of treatment. The CRITICS-II trial aims to optimize preoperative treatment by comparing three treatment regimens: (1) chemotherapy, (2) chemotherapy followed by chemoradiotherapy and (3) chemoradiotherapy.

Methods

In this multicentre phase II non-comparative study, patients with clinical stage IB-IIIC (TNM 8th edition) resectable gastric adenocarcinoma are randomised between: (1) 4 cycles of docetaxel+oxaliplatin+capecitabine (DOC), (2) 2 cycles of DOC followed by chemoradiotherapy (45Gy in combination with weekly paclitaxel and carboplatin) or (3) chemoradiotherapy. Primary endpoint is event-free survival, 1 year after randomisation (events are local and/or regional recurrence or progression, distant recurrence, or death from any cause). Secondary endpoints include: toxicity, surgical outcomes, percentage radical (R0) resections, pathological tumour response, disease recurrence, overall survival, and health related quality of life. Exploratory endpoints include translational studies on predictive and prognostic biomarkers.

Discussion

The aim of this study is to select the most promising among three preoperative treatment arms in patients with resectable gastric adenocarcinoma. This treatment regimen will subsequently be compared with the standard therapy in a phase III trial.

Trial registration

clinicaltrials.gov NCT02931890; registered 13 October 2016. Date of first enrolment: 21 December 2017.

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86.CrossRefPubMed

De Angelis R, Sant M, Coleman MP, Francisci S, Baili P, Pierannunzio D, et al. Cancer survival in Europe 1999-2007 by country and age: results of EUROCARE--5-a population-based study. Lancet Oncol. 2014;15(1):23–34.

Msika S, Benhamiche AM, Jouve J-L, Rat P, Faivre J. Prognostic factors after curative resection for gastric cancer. A population-based study. Eur J Cancer. 2000;36:390–6. https://doi.org/10.1016/S0959-8049(99)00308-1.CrossRefPubMed

Songun I, Putter H, Kranenbarg EMK, Sasako M, van de Velde CJH. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Lancet Oncol. 2010;11:439–49. https://doi.org/10.1016/S1470-2045(10)70070-X.CrossRefPubMed

Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345:725–30.CrossRefPubMed

Smalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, et al. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 2012;30:2327–33.CrossRefPubMedPubMedCentral

Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for Resectable Gastroesophageal Cancer. N Engl J Med. 2006;355:11–20.CrossRefPubMed

Paoletti X, Oba K, Burzykowski T, Michiels S, Ohashi Y, Pignon JP, et al. Benefit of adjuvant chemotherapy for Resectable gastric Cancer. J Am Med Assoc. 2010;303:1729. http://jama.ama-assn.org/content/303/17/1729.short CrossRef

Smyth EC, Verheij M, Allum W, Cunningham D, Cervantes A, Arnold D, et al. Gastric cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27:v38–49.CrossRefPubMed

10.

Dikken JL, van Sandick JW, Maurits Swellengrebel H, Lind PA, Putter H, Jansen EP, et al. Neo-adjuvant chemotherapy followed by surgery and chemotherapy or by surgery and chemoradiotherapy for patients with resectable gastric cancer (CRITICS). BMC Cancer. 2011;11:329. https://doi.org/10.1186/1471-2407-11-329.CrossRefPubMedPubMedCentral

11.

Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, et al. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018;19(5):616–28. https://doi.org/10.1016/S1470-2045(18)30132-3.CrossRefPubMed

12.

Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, et al. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss group for clinical cancer research. J Clin Oncol. 2007;25:3217–23.CrossRefPubMed

13.

Haj Mohammad N, ter Veer E, Ngai L, Mali R, van Oijen MGH, van Laarhoven HWM. Optimal first-line chemotherapeutic treatment in patients with locally advanced or metastatic esophagogastric carcinoma: triplet versus doublet chemotherapy: a systematic literature review and meta-analysis. Cancer Metastasis Rev. 2015;34:429–41.CrossRefPubMedPubMedCentral

14.

Al-Batran SE, Hopmann N, Schmalenberg H, Kopp H-G, Haag GM, Luley KB, et al. Perioperative chemotherapy with docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) versus epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) for resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma (FLOT4-AIO). A mul. J Clin Oncol. 2017;35(15_suppl):4004.CrossRef

15.

Deenen MJ, Meulendijks D, Boot H, Legdeur MCJC, Beijnen JH, Schellens JHM, et al. Phase 1a/1b and pharmacogenetic study of docetaxel, oxaliplatin and capecitabine in patients with advanced cancer of the stomach or the gastroesophageal junction. Cancer Chemother Pharmacol. 2015;76:1285–95.CrossRefPubMed

16.

van Hagen P, Hulshof MCCM, van Lanschot JJB, Steyerberg EW, van B Henegouwen MI, Wijnhoven BPL, et al. Preoperative Chemoradiotherapy for esophageal or Junctional Cancer. N Engl J Med. 2012;366:2074–84. https://doi.org/10.1056/NEJMoa1112088.CrossRefPubMed

17.

Trip AK, Verheij M, van Sandick JW, Boot H, Jansen EP M, Cats A. Emerging issues in multimodality treatment of gastric cancer. Transl Gastrointest Cancer. 2015;4:154–73. https://doi.org/10.3978/j.issn.2224-4778.2015.01.01.CrossRef

18.

Becker K, Mueller JD, Schulmacher C, Ott K, Fink U, Busch R, et al. Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer. 2003;98:1521–30.CrossRefPubMed

19.

Mandard A-M, Dalibard F, Mandard J-C, Marnay J, Henry-Amar M, Petiot J-F, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994;73:2680–6. https://doi.org/10.1002/1097-0142(19940601)73:11<2680::AID-CNCR2820731105>3.0.CO;2-C.CrossRefPubMed

20.

van den Braak RRJ C, van Rijssen LB, van Kleef JJ, Vink GR, Berbee M, van Berge Henegouwen MI, et al. Nationwide comprehensive gastro-intestinal cancer cohorts: the 3P initiative. Acta Oncol. 2018;57:195–202. https://doi.org/10.1080/0284186X.2017.1346381.CrossRef

21.

Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–13.CrossRefPubMedPubMedCentral

22.

Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, et al. Capecitabine and Oxaliplatin for advanced Esophagogastric Cancer. N Engl J Med. 2008;358:36–46. https://doi.org/10.1056/NEJMoa073149.CrossRefPubMed

23.

Case LD, Morgan TM. Design of Phase II cancer trials evaluating survival probabilities. BMC Med Res Methodol. 2003;3:1–12.CrossRef

24.

Lin DY, Shen L, Ying Z, Breslow NE. Group sequential designs for monitoring survival probabilities. Biometrics. 1996;52:1033–41.CrossRefPubMed

25.

Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, et al. Phase III study of Docetaxel and Cisplatin plus fluorouracil compared with Cisplatin and fluorouracil as first-line therapy for advanced gastric Cancer: a report of the V325 study group. J Clin Oncol. 2006;24:4991–7. https://doi.org/10.1200/JCO.2006.06.8429.CrossRefPubMed

26.

Leong T, Smithers BM, Michael M, Gebski V, Boussioutas A, Miller D, et al. TOPGEAR: a randomised phase III trial of perioperative ECF chemotherapy versus preoperative chemoradiation plus perioperative ECF chemotherapy for resectable gastric cancer (an international, intergroup trial of the AGITG/TROG/EORTC/NCIC CTG). BMC Cancer. 2015;15:1–6.CrossRef

27.

Leong T, Smithers BM, Haustermans K, Michael M, Gebski V, Miller D, et al. TOPGEAR: a randomized, phase III trial of perioperative ECF chemotherapy with or without preoperative Chemoradiation for Resectable gastric Cancer: interim results from an international, intergroup trial of the AGITG, TROG, EORTC and CCTG. Ann Surg Oncol. 2017;24:2252–8.CrossRefPubMed

28.

Ikoma N, Das P, Blum M, Estrella JS, Devine CE, Wang X, et al. Preoperative Chemoradiation therapy does not increase risk of anastomotic leak in patients with gastric Cancer. Int J Radiat Oncol Biol Phys. 2017;99:660–6. https://doi.org/10.1016/j.ijrobp.2017.07.018.CrossRefPubMed

29.

Fuchs CS, Enzinger PC, Meyerhardt J, Mayer RJ, Mamon HJ, Swanson RS, et al. Adjuvant chemoradiotlherapy with epirubicin, cisplatin, and fluorouracil compared with adjuvant chemoradiotherapy with fluorouracil and leucovorin after curative resection of gastric cancer: Results from CALGB 80101 (alliance). J Clin Oncol. 2017;35:3671–7.CrossRefPubMedPubMedCentral

30.

Moon JH, Fijiwara Y, Hirao M, Imamura H, Kimura Y, Fijitani K, et al. Randomized controlled trial of adjuvant chemotherapy with Fluoropyrimidines versus surgery-alone for gastric Cancer. Anticancer Res. 2017;37:3061–7.PubMed

31.

Cunningham D, Stenning SP, Smyth EC, Okines AF, Allum WH, Rowley S, et al. Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK medical research council ST03): primary analysis results of a multicentre, open-label, randomised phase 2–3 trial. Lancet Oncol. 2017;18:357–70. https://doi.org/10.1016/S1470-2045(17)30043-8.CrossRefPubMedPubMedCentral

32.

Yoshikawa T, Morita S, Tanabe K, Nishikawa K, Ito Y, Matsui T, et al. Survival results of a randomised two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with two and four courses of S-1 plus cisplatin (SC) and paclitaxel plus cisplatin (PC) followed by D2 gastrectomy for resectable advanced gastric canc. Eur J Cancer. 2016;62:103–11. https://doi.org/10.1016/j.ejca.2016.04.012.CrossRefPubMed

33.

Hashemzadeh S, Pourzand A, Somi MH, Zarrintan S, Javad-Rashid R, Esfahani A. The effects of neoadjuvant chemotherapy on resectability of locally-advanced gastric adenocarcinoma: a clinical trial. Int J Surg. 2014;12:1061–9. https://doi.org/10.1016/j.ijsu.2014.08.349.CrossRefPubMed

34.

Tsuburaya A, Yoshida K, Kobayashi M, Yoshino S, Takahashi M, Takiguchi N, et al. Sequential paclitaxel followed by tegafur and uracil (UFT) or S-1 versus UFT or S-1 monotherapy as adjuvant chemotherapy for T4a/b gastric cancer (SAMIT): a phase 3 factorial randomised controlled trial. Lancet Oncol. 2014;15:886–93. https://doi.org/10.1016/S1470-2045(14)70025-7.CrossRefPubMed

35.

Kang Y-K, Yook JH, Chang H-M, Ryu M-H, Yoo C, Zang DY, et al. Enhanced efficacy of postoperative adjuvant chemotherapy in advanced gastric cancer: results from a phase 3 randomized trial (AMC0101). Cancer Chemother Pharmacol. 2014;73:139–49. https://doi.org/10.1007/s00280-013-2332-5.CrossRefPubMed

36.

Tatebe S, Tsujitani S, Nakamura S, Shimizu T, Yamane N, Nishidoi H, et al. Feasibility study of alternate-day S-1 as adjuvant chemotherapy for gastric cancer: a randomized controlled trial. Gastric Cancer. 2014;17:508–13.CrossRefPubMed

37.

Kang YK, Chang HM, Yook JH, Ryu MH, Park I, Min YJ, et al. Adjuvant chemotherapy for gastric cancer: a randomised phase 3 trial of mitomycin-C plus either short-term doxifluridine or long-term doxifluridine plus cisplatin after curative D2 gastrectomy (AMC0201). Br J Cancer. 2013;108:1245–51.CrossRefPubMedPubMedCentral

38.

Kim TH, Park SR, Ryu KW, Kim YW, Bae JM, Lee JH, et al. Phase 3 trial of postoperative chemotherapy alone versus chemoradiation therapy in stage III-IV gastric cancer treated with R0 gastrectomy and D2 lymph node dissection. Int J Radiat Oncol Biol Phys. 2012;84:e585–92. https://doi.org/10.1016/j.ijrobp.2012.07.2378.CrossRefPubMed

39.

Lee J, Lim DH, Kim S, Park SH, Park JO, Park YS, et al. Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol. 2012;30:268–73.CrossRefPubMed

40.

Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. 2012;379:315–21. https://doi.org/10.1016/S0140-6736(11)61873-4.CrossRefPubMed

41.

Schuhmacher C, Gretschel S, Lordick F, Reichardt P, Hohenberger W, Eisenberger CF, et al. Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European organisation for research and treatment of cancer randomized trial 40954. J Clin Oncol. 2010;28:5210–8.CrossRefPubMedPubMedCentral

42.

Kulig J, Kolodziejczyk P, Sierzega M, Bobrzynski L, Jedrys J, Popiela T, et al. Adjuvant chemotherapy with etoposide, adriamycin and cisplatin compared with surgery alone in the treatment of gastric cancer: a phase III randomized, multicenter, clinical trial. Oncology. 2010;78:54–61.CrossRefPubMed

43.

Bamias A, Karina M, Papakostas P, Kostopoulos I, Bobos M, Vourli G, et al. A randomized phase iii study of adjuvant platinum/docetaxel chemotherapy with or without radiation therapy in patients with gastric cancer. Cancer Chemother Pharmacol. 2010;65:1009–21.CrossRefPubMed

44.

Biffi R, Fazio N, Luca F, Chiappa A, Andreoni B, Zampino MG, et al. Surgical outcome after docetaxel-based neoadjuvant chemotherapy in locally-advanced gastric cancer. World J Gastroenterol. 2010;16:868–74.PubMedPubMedCentral

45.

Schwartz GK, Winter K, Minsky BD, Crane C, Thomson PJ, Anne P, et al. Randomized phase II trial evaluating two paclitaxel and cisplatin-containing chemoradiation regimens as adjuvant therapy in resected gastric cancer (RTOG-0114). J Clin Oncol. 2009;27:1956–62.CrossRefPubMedPubMedCentral

46.

Di Costanzo F, Gasperoni S, Manzione L, Bisagni G, Labianca R, Bravi S, et al. Adjuvant chemotherapy in completely resected gastric cancer: a randomized phase III trial conducted by GOIRC. J Natl Cancer Inst. 2008;100:388–98.CrossRefPubMed

47.

Jeung HC, Moon YW, Rha SY, Yoo NC, Roh JK, Noh SH, et al. Phase III trial of adjuvant 5-fluorouracil and adriamycin versus 5-fluorouracil, adriamycin, and polyadenylic-polyuridylic acid (poly a:U) for locally advanced gastric cancer after curative surgery: final results of 15-year follow-up. Ann Oncol. 2008;19:520–6.CrossRefPubMed

48.

Nakajima T, Kinoshita T, Nashimoto A, Sairenji M, Yamaguchi T, Sakamoto J, et al. Randomized controlled trial of adjuvant uracil-tegafur versus surgery alone for serosa-negative, locally advanced gastric cancer. Br J Surg. 2007;94:1468–76.CrossRefPubMed

49.

De Vita F, Giuliani F, Orditura M, Maiello E, Galizia G, Di Martino N, et al. Adjuvant chemotherapy with epirubicin, leucovorin, 5-fluorouracil and etoposide regimen in resected gastric cancer patients: a randomized phase III trial by the Gruppo Oncologico Italia Meridionale (GOIM 9602 study). Ann Oncol. 2007;18:1354–8.CrossRefPubMed

50.

Cascinu S, Labianca R, Barone C, Santoro A, Carnaghi C, Cassano A, et al. Adjuvant treatment of high-risk, radically resected gastric cancer patients with 5-fluorouracil, leucovorin, cisplatin, and epidoxorubicin in a randomized controlled trial. J Natl Cancer Inst. 2007;99:601–7.CrossRefPubMed

51.

Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, et al. Adjuvant chemotherapy for gastric Cancer with S-1, an oral Fluoropyrimidine. N Engl J Med. 2007;357:1810–20. https://doi.org/10.1056/NEJMoa072252.CrossRefPubMed

52.

Nishikawa T, Maetani S. Evaluation of intensive adjuvant chemotherapy in gastric cancer using life expectancy compared with log-rank test as a measure of survival benefit. Ann Surg Oncol. 2007;14:348–54.CrossRefPubMed

53.

Bouché O, Ychou M, Burtin P, Bedenne L, Ducreux M, Lebreton G, et al. Adjuvant chemotherapy with 5-fluorouracil and cisplatin compared with surgery alone for gastric cancer: 7-year results of the FFCD randomized phase III trial (8801). Ann Oncol. 2005;16:1488–97.CrossRefPubMed

54.

Nashimoto A, Nakajima T, Furukawa H, Kitamura M, Kinoshita T, Yamamura Y, et al. Randomized trial of adjuvant chemotherapy with mitomycin, fluorouracil, and cytosine arabinoside followed by oral fluorouracil in serosa-negative gastric cancer: Japan clinical oncology group 9206-1. J Clin Oncol. 2003;21:2282–7.CrossRefPubMed

55.

Cirera L, Balil A, Batiste-Alentorn E, Tusquets I, Cardona T, Urcusa A, et al. Randomized clinical trial of adjuvant Mytomycin plus Tegafur in patients with resected stage III gastric Cancer. J Clin Oncol. 1999;17:3810–5.CrossRefPubMed

56.

Nakajima T, Nashimoto A, Kitamura M, Kito T, Iwanaga T, Okabayashi K, et al. Adjuvant mitomycin and fluorouracil followed by oral uracil plus tegafur in serosa-negative gastric cancer: a randomised trial. Lancet. 1999;354:273–7.CrossRefPubMed

57.

Lise M, Nitti D, Marchet A, Sahmoud T, Buyse M, Duez N, et al. Final results of a phase III clinical trial of adjuvant chemotherapy with the modified fluorouracil, doxorubicin, and mitomycin regimen in resectable gastric cancer. J Clin Oncol. 1995;13:2757–63.CrossRefPubMed

58.

Macdonald JS, Fleming TR, Peterson RF, Berenberg JL, McClure S, Chapman RA, et al. Adjuvant chemotherapy with 5-FU, adriamycin, mitomycin-C (FAM) versus surgery alone for patients with locally advanced gastric adenocarcinoma: a southwest oncology group study. Ann Surg Oncol. 1995;2:488–94.CrossRefPubMed

59.

Park SH, Sohn TS, Lee J, Lim DH, Hong ME, Kim KM, et al. Phase III trial to compare adjuvant chemotherapy with capecitabine and cisplatin versus concurrent chemoradiotherapy in gastric cancer: final report of the adjuvant chemoradiotherapy in stomach tumors trial, including survival and subset analyses. J Clin Oncol. 2015;33:3130–6.CrossRefPubMed

Title: CRITICS-II: a multicentre randomised phase II trial of neo-adjuvant chemotherapy followed by surgery versus neo-adjuvant chemotherapy and subsequent chemoradiotherapy followed by surgery versus neo-adjuvant chemoradiotherapy followed by surgery in resectable gastric cancer
Authors: Astrid E. Slagter
Edwin P. M. Jansen
Hanneke W. M. van Laarhoven
Johanna W. van Sandick
Nicole C. T. van Grieken
Karolina Sikorska
Annemieke Cats
Pietje Muller-Timmermans
Maarten C. C. M. Hulshof
Henk Boot
Maartje Los
Laurens V. Beerepoot
Frank P. J. Peters
Geke A. P. Hospers
Boudewijn van Etten
Henk H. Hartgrink
Mark I. van Berge Henegouwen
Grard A. P. Nieuwenhuijzen
Richard van Hillegersberg
Donald L. van der Peet
Heike I. Grabsch
Marcel Verheij
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-018-4770-2

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