Oxaliplatin Plus Capecitabine in the Perioperative Treatment of Locally Advanced Gastric Adenocarcinoma (Neo-Classic)

A Multicenter, Single Arm, Open-label Trial of Oxaliplatin Plus Capecitabine (XELOX) in the Perioperative Treatment of Locally Advanced Gastric Adenocarcinoma

1. Target population:locally advanced gastric adenocarcinoma (LAGC, cT2~3/N+M0,or cT4aN+M0);no previous chemo or radio therapy.

2. Primary objective:Response rate of XELOX in the neoadjuvant setting of LAGC.

   Secondary objectives:

   • The progression free survival (PFS) in the perioperative treatment of locally advanced gastric adenocarcinoma (cT3/N+M0,or cT4aN+M0);
   • percentage of pathological response ; percentage of grade 3 or 4 adverse events as safety profile of perioperative treatments;
   • D2 resection -rate after neoadjuvant chemotherapy of XELOX;
   • Overall survival;
   • QOL during the whole period of treatment.
3. Trial design:This is a multicenter, single arm, open-label, phase II study to evaluate the efficacy and safety of Oxaliplatin plus capecitabine(XELOX) in the perioperative treatment of locally advanced gastric adenocarcinoma in combination with D2 resection.
4. Treatment plan:Patients will be given the perioperative chemotherapy as below once recruited:Schedule of Oxaliplatin plus capecitabine (XELOX) will be as follow: Capecitabine 1000 mg/m2 ，bid,d 1~14 every 3 weeks(treatment for 2 weeks and rest 1 week)Oxaliplatin：130mg/m2， iv infusion over 2h，d1,every 3 weeks.
5. Number of subjects:50 patients.Number of centers 5 sites, which have the high volume of gastric operations in China, more than 500 per year.

Study Overview

• Status: Unknown
• Conditions: Gastric Adenocarcinoma
• Intervention / Treatment: Drug: XELOX

Detailed Description

1. Disease specific inclusion criteria:

   • Histologically documented gastricadenocarcinoma with Lauren classification Clinically diagnosed stage T2-3/N+M0,orT4aN+M0 according to CT/MRI scan, and resectable
   • Measurable disease is required
   • Karnofsky score 80%.
   • Physical condition and adequate organ function to ensure the success of abdominal surgery.
   • Life expectancy ≥12 weeks.
   • Adequate hematological function: Neutrophil count ≥ 1.5 × 109/L, Platelets ≥ 100 × 109/L and Hemoglobin ≥8g/dL .Adequate liver function: Total bilirubin ≤ 1.5 × upper limit of normal (ULN); AST (SGOT) and ALT (SGPT) < 2.5 × ULN in the absence of liver metastases, or < 5 × ULN in case of liver metastases. ALP ≤ 2.5 × upper limit of normal (ULN); ALB ≥30g/L.

   Adequate renal function: Serum creatinine ≤ 1.25 x ULN, and creatinine clearance ≥ 60 ml/min.

   • Female subjects should not be pregnant or breast-feeding.
   • No serious concomitant disease that will threaten the survival of patients to less than 5 years.

2. General inclusion criteria:

   • Male or female. Age ≥ 18 years and ≤75 years
   • Written (signed) informed consent.
   • Able to comply with study and follow-up procedures.
   • Good compliance with the treatment plan。
   • Consent to provide tissue sample。

• Study Type: Interventional
• Enrollment (Anticipated): 55
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Zhongshan Hospital Affiliated to Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically documented gastricadenocarcinoma with Lauren classification Clinically diagnosed stage T2-3/N+M0,orT4aN+M0 according to CT/MRI scan, and resectable
• Measurable disease is required
• Karnofsky score 80%.
• Physical condition and adequate organ function to ensure the success of abdominal surgery.
• Life expectancy ≥12 weeks.
• Adequate hematological function: Neutrophil count ≥ 1.5 × 109/L, Platelets ≥ 100 × 109/L and Hemoglobin ≥8g/dL .Adequate liver function: Total bilirubin ≤ 1.5 × upper limit of normal (ULN); AST (SGOT) and ALT (SGPT) < 2.5 × ULN in the absence of liver metastases, or < 5 × ULN in case of liver metastases. ALP ≤ 2.5 × upper limit of normal (ULN); ALB ≥30g/L.Adequate renal function: Serum creatinine ≤ 1.25 x ULN, and creatinine clearance ≥ 60 ml/min.
• Female subjects should not be pregnant or breast-feeding.
• No serious concomitant disease that will threaten the survival of patients to less than 5 years.
• Male or female.
• Age ≥ 18 years and ≤75 years
• Written (signed) informed consent.
• Able to comply with study and follow-up procedures.
• Good compliance with the treatment plan.
• Consent to provide tissue sample.

Exclusion Criteria:

• Pregnant or lactating (in case of potentially childbearing woman, pregnancy test is positive)
• Patients of child-bearing age or the potential to father a child who refuse to use adequate contraception
• Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
• History of another malignancy in the last 5 years with the exception of the following:

Any previous palliative, adjuvant or neoadjuvant chemotherapy and/or radiotherapy. Prior treatment for locally advanced or metastatic gastric cancer. Any metastatic disease will render patient ineligible according to AJCC staging manual.

• Distant metastases (M1) including distant nodal Groups (peripancreatic, para-aortic, portal, retroperitoneal, mesenteric node, by CT/MRI, or PET/CT
• Treatment within the last 30 days with any investigational drug. Concurrent administration of any other cancer therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.
• Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
• Poorly controlled diabetes mellitus with fasting blood sugar > 18 mM. Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
• History of significant neurological or mental disorder, including seizures or dementia, which would interfere compliance and sign of consent inform. any history of hypersensitivity to 5-fluorouracil or platinum and other investigational drug
• Ileus, chronic inflammatory intestinal disease or extensive resection of the small intestine and other disorders which limit drug reabsorption. This includes gastric dumping syndrome, indications of accelerated passage through the small intestine, indications of reabsorption disorders after intestinal surgery
• Unstable, persistent cardiac disease despite medicinal treatment, myocardial infarction within 6 months before the start of the trial
• Organ transplant patient need immunosuppression treatment.
• Previous surgery on primary tumour; Prior palliative surgery (open and closure, passage operation)
• Any other type of tumour (e.g. leiomyosarcoma, lymphoma) or a secondary malignancy, excepting basal cell skin carcinoma or basal cell carcinoma in situ of the cervix which have already been successfully treated
• Symptomatic peripheral neuropathy NCI CTC version> 3.0 grade.
• Patients under anticoagulant therapy with warfarin or other coumarines are excluded from participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: XELOX; Clinically diagnosed stage T2-3/N+M0,orT4aN+M0 according to CT/MRI scan, and resectable

Drug: XELOX; Patients will be given the perioperative chemotherapy as below once recruited: Capecitabine ：500 mg tablets（Roche） Oxaliplatin：50mg/10ml（according to daily practice in each center） Schedule of Oxaliplatin plus capecitabine (XELOX) will be as follow: Capecitabine 1000 mg/m2 ，orally taken 30 minutes after meal, bid ， d 1~14 every 3 weeks(treatment for 2 weeks and rest 1 week) Oxaliplatin：130mg/m2， iv infusion over 2h，d1,every 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the response rate of XELOX in the neoadjuvant setting of LAGC	the response rate evaluation will be based on tumor assessment with follow-up, including chest and upper-abdominal During preoperative treatment period, CT scan will be performed every 6 -8 weeks (2 cycles after)., brain MRI and bone scan (ECT) will be performed if any suspected symptoms occur.	6 months after the last subject participating in

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the progression free survival (PFS) in the perioperative treatment of locally advanced gastric adenocarcinoma (cT2-3/N+M0,or cT4aN+M0)	progression by the evidence of CT/MRI scan at each evaluation at neoadjuvant period or follow-up time after surgery；During preoperative treatment period, CT scan will be performed every 6 -8 weeks (2 cycles after).After syrgery, CT scan will be planned every 6 months, brain MRI and bone scan (ECT) will be performed if any suspected symptoms occur.	42 months after the last subject participating in
percentage of pathological response	After surgery，the pathological response will be measured by the pathologist for every Operation patient.	10 months after the last subject participating in
Percentage of grade 3 or 4 adverse events as safety profile of perioperative treatments	Adverse events and clinical laboratory tests will be recorded by CTCAE (version 4.0) during the whole treatment period.	1 month after the last date of treatment
Overall survival	During the OS follow-up, out-patient clinic and telephone visit will be done every 3 months for the first two years, and every 6 months after two years.	3 years after the last subject participating in
QOL during the whole period of treatment	These assessment will be evaluated at every evaluation.	1 years after the last date of treatment

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Collaborators: Fudan University; RenJi Hospital; Ruijin Hospital; Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
• Investigators: Principal Investigator: Tianshu Liu, Doctor, Medical oncology Shanghai zhongshan hospital

Publications and helpful links

General Publications

• Yu Y, Fang Y, Shen Z, Wang Y, Yan M, Cao H, Liu Y, Wang X, Cui Y, Liu F, Chen W, Li W, Li Q, Jiang H, Sun Y, Liu T. Oxaliplatin plus Capecitabine in the Perioperative Treatment of Locally Advanced Gastric Adenocarcinoma in Combination with D2 Gastrectomy: NEO-CLASSIC Study. Oncologist. 2019 Oct;24(10):1311-e989. doi: 10.1634/theoncologist.2019-0416. Epub 2019 Jun 25.

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Anticipated): May 1, 2016
• Study Completion (Anticipated): August 1, 2018

Study Registration Dates

• First Submitted: June 8, 2013
• First Submitted That Met QC Criteria: June 15, 2013
• First Posted (Estimate): June 19, 2013

Study Record Updates

• Last Update Posted (Estimate): December 18, 2015
• Last Update Submitted That Met QC Criteria: December 17, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: XELOX; D2 resection; perioperative treatment; locally advanced gastric adenocarcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma
• Other Study ID Numbers: ML28733