Locally Advanced Gastric CancerPhase 3Neo-D2plusNCT03961373
Standard Versus Super-extended Lymphadenectomy After Neo-adjuvant Chemotherapy for Gastric Cancer
A Phase 3 study testing Gastrectomy with D2 lymphadenectomy and Gastrectomy with D2plus lymphadenectomy in people with Locally Advanced Gastric Cancer, run by University of Siena at 1 site in Italy.
Trial summary
In this study the patients with histological evidence of adenocarcinoma of the stomach will be screened and, if eligible, submitted to neo-adjuvant chemotherapy (NAC). After conclusions of NAC and obtaining informed consent, they will be registered and randomized to receive surgical D2 vs. D2plus lymphadenectomy. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Locally Advanced Gastric Cancer
- What is being tested?
- Gastrectomy with D2 lymphadenectomy and Gastrectomy with D2plus lymphadenectomy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 539 participants
- Where
- 1 siteItaly
- Study dates
- 5 Nov 2018to 1 Nov 2028
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age equal or greater than 18 years
- IIA-IIIC histologically proven primary gastric adenocarcinoma, before the treatment with NAC. Not including gastro-oesophageal junction/cardia carcinoma but only Siewert 3, without any previous treatment (surgery and / or chemotherapy) for this diagnosis
- Lack in CT scan of following:
- Mediastinal lymph nodes
- Lung metastases
- Peritoneal metastases
Show all 19Show fewer
- Liver metastases
- Pleural effusion, ascites
- Metastases to para-aortic lymph nodes No 16a2/b1
- Metastases to lymph nodes located in the "posterior" area (8p, 12 b/p, 13)
- Extra-regional lymph node metastases
- ECOG performance status ≤ 2
- No prior radio- or chemotherapy conflicting with the treatment of gastric cancer
- No oesophageal invasion, or invasion <=3cm
- Negative peritoneal washing cytology findings and no peritoneal metastases in staging laparoscopy
- No gastric stump cancer
- No signs of cervical and subclavear lymph nodes or distal metastases
- Patient's consent form obtained, signed and dated before beginning specific protocol procedures
- Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
Who cannot join
- Contraindications for any sort of appropriate chemotherapy according to local standards
- Linitis plastica
- Second uncontrolled malignant tumour (synchronous or metachronous (last 5 years) other than Cis or mucosal cancer
- Neoplasms involving the esophago-gastric junction (Siewert types I and II)
- Expected unresectability after neo-adjuvant treatment or progression in metastases
- Emergency surgery due to bleeding or perforation
Show all 15Show fewer
- Uncontrolled infections
- Other serious underlying medical conditions that could impair the ability of the patient to participate in the study
- Pregnant or lactating women
- Significant neurologic or psychiatric disorders
- Severe cardiac illness (NYHA class IV)
- Under treatment of systemic steroids
- Participation in any other clinical trial that might interfere with the results of this trial
- Lack of compliance
- Inability to fill in questionnaires (insufficient command of language, dementia, lack of time)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
General and Surgical Oncology Department, University of Siena
Siena, 53100
Daniele Marrelli, +39577585157, daniele.marrelli@unisi.it
About this study
In this study the patients with histological evidence of adenocarcinoma of the stomach will be screened and, if eligible, submitted to neo-adjuvant chemotherapy (NAC). After conclusions of NAC and obtaining informed consent, they will be registered and randomized to receive surgical D2 vs. D2plus lymphadenectomy.
Read the detailed description
This is a prospective multi-centre phase III, two-group, randomized and controlled trial designed to prove superiority of the experimental treatment arm (neo-adjuvant chemotherapy and super-extended lymphadenectomy).
The trial population consists of patients who have histologically confirmed adenocarcinoma of the stomach with locally advanced primary tumour and no evidence of distant metastases (stage IIA-IIIC gastric cancer). The lymph node clinical metastases, before neo-adjuvant chemotherapy, must be limited to the first and second compartments (stations 1-12).
STANDARD GROUP: Neoadjuvant chemotherapy + surgical gastrectomy with D2 lymphadenectomy.
Patients who are assigned to neoadjuvant chemotherapy+ surgical D2 treatment group will undergo either subtotal or total gastrectomy, depending on the location of the primary tumour. Standardized D2-lymph node dissection is required with specific information about lymph node stations.
EXPERIMENTAL GROUP: Neoadjuvant chemotherapy + surgical gastrectomy with D2plus lymphadenectomy.
Patients who are assigned to neoadjuvant chemotherapy + surgical D2plus extended lymphadenectomy treatment group will undergo either subtotal or total gastrectomy, depending on the location of the primary tumour. Standardized D2 lymph node dissection plus resection of stations 8p, 12b/p, 13, 14v, 16a2/b1 is required with specific information about lymph node stations.
In both groups, surgical treatment should be performed within 4-6 weeks after the end of the last cycle of NAC.
The primary objective of this study is to compare overall and cancer-related survival between D2 and D2+ lymphadenectomy following neo-adjuvant chemotherapy for resectable gastric cancer.
In addition, response to chemotherapy, resection rate, quality of life, complications attributable to surgical intervention / side effects of chemotherapy and the duration of hospitalization will be evaluated.
Sample size estimation was performed, to detect the minimum number of patients to be recruited in each arm. A two-sided log rank test with an overall sample size of 539 subjects, of which 270 are in group 1 and 269 are in group 2.
Data will be analyzed using SPSS software. Level of significance will be defined as 5%.
The trial will be open for recruitment from October 2018 to September 2023.
- Conditions
- Locally Advanced Gastric Cancer
- Being tested
- Gastrectomy with D2 lymphadenectomy, Gastrectomy with D2plus lymphadenectomy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gastrectomy with D2 lymphadenectomyProcedure or surgery
Patients who are assigned to the neoadjuvant chemotherapy+ surgical D2 treatment group will undergo either subtotal or total gastrectomy, depending on the location of the primary tumour. Standardized D2-lymph node dissection is required with specific information about lymph node stations.
Gastrectomy with D2plus lymphadenectomyProcedure or surgery
Patients who are assigned to the neoadjuvant chemotherapy + surgical D2+ extended lymphadenectomy treatment group will undergo either subtotal or total gastrectomy, depending on the location of the primary tumour. Standardized D2+ lymph node dissection plus resection of stations 8p, 12p, 13, 14v, 16a2/b1 is required with specific information about lymph node stations.
| Study group | Role | What they receive |
|---|---|---|
| Standard Group | Active comparator | Neoadjuvant chemotherapy + surgical gastrectomy with D2 lymphadenectomy Receives: Procedure: Gastrectomy with D2 lymphadenectomy |
| Experimental Group | Experimental | Neoadjuvant chemotherapy + surgical gastrectomy with D2plus lymphadenectomy Receives: Procedure: Gastrectomy with D2plus lymphadenectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival analysis
Overall survival analysis will be analysed during follow up visits
Measured: This outcome measure will be estimated from the time of randomization to the date of death or last follow up visit, assessed approximately 5 years after the disease diagnosis.
Secondary outcomes (5)
Recurrence free-survival
That part will also be analysed during follow up visits. The recurrence has to be documented in radiological, endoscopic or pathological examination, when possible.
Measured: This outcome measure will be estimated from the time of randomization to the date of recurrence, assessed approximately 5 years after the disease diagnosis.
Post-operative morbidity
Severity of post-operative complications will be analysed using Clavien-Dindo classification
Measured: This outcome measure will be assessed approximately 3 month after the operation date.
Post-operative mortality
Deaths after surgery
Measured: Within 30 days from operation or during the hospital stay
R0 resection
Absence of microscopic (R1) or macroscopic (R2) residual tumor after surgery
Measured: This outcome measure will be assessed approximately 3 month after the operation date.
Percentage of completion of protocol treatment
Percentage of patients who will complete the protocol treatment, including adjuvant chemotherapy
Measured: This outcome measure will be assessed approximately 12 month after the date of enrollment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2019
- Study start5 Nov 2018
- Primary completion1 Nov 2023 (estimated)
- Study completion1 Nov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced Gastric CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 539 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Siena
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Franco Roviello, University of Siena
- Investigators
- Franco Roviello, Principal investigator, University of Siena
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03961373
- Sponsor's protocol ID
- Neo-D2plus trial
- Acronym
- Neo-D2plus
- Status last verified
- May 2019
- First submitted
- 12 Mar 2019
- Last updated
- 23 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No