Apatinib Plus XELOX as Neoadjuvant Therapy in Locally Advanced Gastric Cancer

Study Overview
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Brief Summary
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Apatinib plus XELOX regime as Neoadjuvant Therapy in Locally Advanced Gastric Cancer PatientsWith lymph node metastasis

Detailed Description
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This is a Single-center, Open-label, Single-arm,Non-randomized exploratory clinical trial evaluating the efficacy and safety of Apatinib plus XELOX regime as Neoadjuvant Therapy in Locally Advanced Gastric Cancer Patients With lymph node metastasis

Official Title
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Apatinib Plus XELOX Regime as Neoadjuvant Therapy in Locally Advanced Gastric Cancer Patients With Lymph Node Metastasis

Conditions
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Gastric Cancer, Chemotherapy Effect, Chemotherapeutic Toxicity

Intervention / Treatment
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* Drug: Apatinib plus XELOX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, age ≥18 years. Karnofsky score 70%. Histologically confirmed adenocarcinoma of gastric cancer with Lauren classification Clinically diagnosed stage T2-T4aN+M0 according to CT/MRI scan. At least one measurable and evaluable disease based on response evaluation criteria in solid tumors (RECIST v1.1), that is one or more perigastric lymph note were greater than or equal to 1.5cm in diameter. Laparoscopic exploration confirms no peritoneal metastasis and negative peritoneal lavage. Physical condition and adequate organ function to ensure the success of abdominal surgery. 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. ALP ≤ 2.5 × upper limit of normal (ULN); ALB ≥30g/L.Adequate renal function: Serum creatinine ≤ 1 x ULN, and serum albumin≥30g/L. Life expectancy of more than 5 years without serious concomitant diseases. Written (signed) informed consent. Able to comply with study and follow-up procedures. Consent to provide tissue sample. Exclusion Criteria: Pregnant or lactating women. pregnancy tests before entering the group (in serum) of the childbearing age women were positive, or no pregnancy tests. patients with distant metastases or local unresectable factors. tumor stage considered as cT1 by imaging or ultrasound gastroscopy. Patients who received prior anti-tumor therapy including cytotoxic chemotherapy, radiotherapy, hormonal therapy and immunotherapy. History of other malignancies within the last 5 years except cured basal cell carcinoma of skin and carcinoma in situ of uterine cervix. History of significant neurological or mental disorder, including seizures or dementia, which may interfere compliance and sign of consent inform. Unstable, persistent cardiac disease despite medicinal treatment; myocardial infarction within 12 months before the start of the trial. Patients with poor-controlled arterial hypertension (systolic pressure ≥ 140 mmHg and/or diastolic pressure ≥ 90 mm Hg) despite standard medical management. Ileus, chronic inflammatory intestinal disease or extensive resection of the small intestine and other disorders which limit drug absorption. Patients who experienced GI bleeding within two weeks, or with high risk of bleeding. Patients with symptomatic peripheral neuropathy NCI CTC version> 1.0 grade, except only the deficiency of Deep tendon reflex. Organ transplant patient need immunosuppression treatment. Active or uncontrolled severe infection or other severe and /or uncontrolled diseases Patients with moderate or severe chronic kidney disease estimated glomerular filtration rate≤50 ml/min or serum creatinine ≥the upper limit of normal(ULN), deficiency of dihydropyrimidine dehydrogenase (DPD) Allergy to the drugs in this protocol Less than 4 weeks from the last clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apatinib plus XELOX<br>Patients will be given the perioperative chemotherapy of Apatinib plus XELOX once recruited | Drug: Apatinib plus XELOX<br>* three weeks is one cycle, 4 cycles followed by radical gastrectomy. Apatinib: 250 mg, p.o., qd, every 3 weeks for the first two cycles. if no level 3 or severer AEs happened, change apatinib to 500mg, p.o.,qd, otherwise keep 250mg in the third cycle. no apatinib in the fourth cycle. Capecitabine: 1000mg/m2, p.o., bid, D1-14, every 3 weeks (treatment for 2 weeks and rest 1 week). Oxaliplatin: 130mg/m2, i.v. over 2h, D1, every 3 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Both CR and PR according to Response Evaluation Criteria in Solid Tumors RECIST Version 1.1 | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | The safety of the the perioperative treatment, percentage of grade 3 or 4 adverse events as safety profile of perioperative treatments | 30 days | 
| Pathological response rate (pRR) | Briefly, pathCR (Pathological complete rate) was defined as an absence of carcinoma cells in the primary site, and pathologic partial response (pathPR) was defined as less than 10% residual carcinoma cells in the specimen. | 30 days | 
| 3-year disease free survival rate |  | 3 years | 
| 3-year overall survival rate |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gastric cancer, neoadjuvant chemotherapy, apatinib