Upfront Surgery Versus NeoAdjuvant Chemotherapy Followed by Surgery for Resectable Advanced Gastric Cancer: SNAC Study (SNAC)

Upfront Surgery Versus NeoAdjuvant Chemotherapy Followed by Surgery for Resectable Advanced Gastric Cancer (SNAC Study): An Observational Retrospective Multicenter Study With Matched Treatment Comparison

Based on the concerns about the actual low strength of evidence of the efficacy of NAC on survival of proper gastric cancer treated with adequate D2 gastrectomy as compared to the results of optimal upfront surgery (S), and considering the actual difficulties of additional RCTs, the aim of this study is to assess the non-inferiority of upfront surgery alone with optimal D2 dissection compared to NAC regimens followed by surgery. Methods: This is a nationwide Multicenter observational retrospective study with matched comparison of two therapeutic strategies (NAC vs S). We will include patients with cT>2, every cN M0, or with every T and N+ M0, histologically proven adenocarcinoma of the stomach, submitted either to pre- or peri-operative treatment and D2 gastrectomy or to upfront D2 gastrectomy, between January 2012 and December 2019, followed by adjuvant treatment when recommended.

All patients matching the inclusion/exclusion criteria will be registered into the study and classified into one of the two arms: a, patients who underwent pre- or perioperative treatment and D2 gastrectomy (NAC) or b, patients submitted to upfront D2 gastrectomy (S). Given the results reported in the "FLOT" trial, a 3-years OS of 55% in the control arm (NAC) was assumed. Three-year OS in the experimental arm (S) was assumed to be 47.4% under the null hypothesis of inferiority and 55% under the alternative hypothesis of non-inferiority. A sample size of 684 patients (342 in each arm) achieves 80% power to detect a non-inferiority margin Hazard Ratio of 1.25

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer
• Intervention / Treatment: Other: pre- or perioperative treatment and D2 gastrectomy

• Study Type: Observational
• Enrollment (Estimated): 684

Contacts and Locations

• Study Contact: Name: Rossella Reddavid, MD; Phone Number: +393479848651; Email: rossella.reddavid@unito.it

Study Locations

• Italy
  • Piedmont
    • Orbassano, Piedmont, Italy, 10043
      • Recruiting
      • San Luigi University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

4.1.1. This is a nationwide Multicenter observational retrospective study with matched comparison of two therapeutic strategies (NAC vs upfront surgery). Participating centers should have a hospital volume of at least 20 gastric resections for stomach cancer per year. We will include a) patients with cT>2, every cN, or b) patients with every T and N+, histologically proven adenocarcinoma of the stomach without distant metastases (M0) and without involvement of adjacent structures/organs, submitted either to pre- or peri-operative treatment and D2 gastrectomy or to upfront D2 gastrectomy, between January 2012 and December 2019, followed by adjuvant treatment when recommended. All patients who meet the inclusion/exclusion criteria will be registered into the study and classified to one of the two arms based on their treatment (a. Patients who underwent pre- or perioperative treatment and D2 gastrectomy - NAC or b. Patients submitted to upfront D2 gastrectomy- S).

Description

Inclusion Criteria:

• 3.1.1. Locally advanced (T>2 any N or N+ any T) histologically proven adenocarcinoma of the stomach without distant metastases (M0) and without infiltration of adjacent structures and organs.

3.1.2. D2 lymphadenectomy (based on Japanese gastric cancer guideline) 3.1.3. Age > 18 years 3.1.4. surgical resectability 3.1.5. follow-up time of at least 36 months.

Exclusion Criteria:

3.2.1. distant metastases (cM+) or infiltration of adjacent structures or organs (cT4b) and all primarily not resectable stages 3.2.2. Other types of lymphadenectomy lower than D2 3.2.3. Siewert type I and II Cardia cancers 3.2.2. Relapsed gastric cancers 3.2.3. malignant secondary disease, dated back < 5 years (exception: In-situ-carcinoma of the cervix uteri, adequately treated skin basal cell carcinoma)

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Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
upfront D2 gastrectomy (S); patients submitted to upfront D2 gastrectomy
pre- or perioperative treatment and D2 gastrectomy (NAC); patients who underwent pre- or perioperative treatment and D2 gastrectomy	Other: pre- or perioperative treatment and D2 gastrectomy; pre- or perioperative treatment and D2 gastrectomy; Other Names: perioperative treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
overall survival	3- and 5- year follow-up

Secondary Outcome Measures

Outcome Measure	Time Frame
R0-Resection rate	2 months after surgery
disease free survival (DFS)	[ Time Frame: 2-year follow-up ]
Perioperative Morbidity and Mortality	Time Frame: up to 2 months after surgery
Rate of NAC patients submitted to surgery	3 years
Rate of NAC patients completing postoperative treatment	3 years

Collaborators and Investigators

• Sponsor: San Luigi Gonzaga Hospital
• Collaborators: Azienda Ospedaliera Città della Salute e della Scienza di Torino; Fondazione Policlinico Universitario Agostino Gemelli IRCCS; Federico II University; Ospedale San Donato; Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico; Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia; Istituti Ospitalieri di Cremona; Ospedale di Circolo - Fondazione Macchi; Azienda Ospedaliera di Padova; University of Florence; Azienda Ospedaliera di Perugia; Azienda Ospedaliero-Universitaria di Parma; Azienda Ospedaliera Universitaria Senese; Azienda Ospedaliero-Universitaria Careggi; Humanitas Hospital, Italy; A.O. Ospedale Papa Giovanni XXIII; Azienda Ospedaliera San Gerardo di Monza; Istituti Tumori Giovanni Paolo II; Istituto Europeo di Oncologia; Fondazione IRCCS Policlinico San Matteo di Pavia; Azienda ULSS di Verona e Provincia; Policlinico Abano Terme; Azienda Ospedaliera OO.RR. S. Giovanni di Dio e Ruggi D'Aragona; Ospedale M. Bufalini Cesena; Provincia Autonoma di Trento; IRCCS Ospedale San Raffaele; Ospedale Santo Stefano; ASST Grande Ospedale Metropolitano Niguarda; Azienda Ospedaliero Universitaria Policlinico Modena; Azienda Ospedaliera, Ospedale Sant'Anna-Como; Government hospital in Forlì, Italy; Ospedale Guglielmo da Saliceto, Piacenza

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2022
• Primary Completion (Actual): August 30, 2023
• Study Completion (Estimated): September 30, 2024

Study Registration Dates

• First Submitted: June 18, 2024
• First Submitted That Met QC Criteria: June 23, 2024
• First Posted (Actual): June 24, 2024

Study Record Updates

• Last Update Posted (Actual): June 24, 2024
• Last Update Submitted That Met QC Criteria: June 23, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: D2 lymphadenectomy; upfront surgery; perioperative treatment
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: SNAC01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No