Clinical trial NCT01880632: Oxaliplatin Plus Capecitabine in the Perioperative Treatment of Locally Advanced Gastric Adenocarcinoma
Official title: A Multicenter, Single Arm, Open-label Trial of Oxaliplatin Plus Capecitabine (XELOX) in the Perioperative Treatment of Locally Advanced Gastric Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Gastric Adenocarcinoma
Keywords: XELOX
perioperative treatment
locally advanced gastric adenocarcinoma
D2 resection
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
Collaborators: name: Ruijin Hospital
name: RenJi Hospital
name: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
name: Fudan University
First posted: 2013-06-19
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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。

Eligibility criteria: 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.

Primary outcomes:
measure: the response rate of XELOX in the neoadjuvant setting of LAGC
timeFrame: 6 months after the last subject participating in
Secondary outcomes:
measure: the progression free survival (PFS) in the perioperative treatment of locally advanced gastric adenocarcinoma (cT2-3/N+M0,or cT4aN+M0)
timeFrame: 42 months after the last subject participating in
measure: percentage of pathological response
timeFrame: 10 months after the last subject participating in
measure: Percentage of grade 3 or 4 adverse events as safety profile of perioperative treatments
timeFrame: 1 month after the last date of treatment
measure: Overall survival
timeFrame: 3 years after the last subject participating in
measure: QOL during the whole period of treatment
timeFrame: 1 years after the last date of treatment
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Zhongshan Hospital Affiliated to Fudan University
state: Shanghai
Study officials:
affiliation: Medical oncology Shanghai zhongshan hospital
name: Tianshu Liu, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.