Comparative Study of Lobaplatin and Paclitaxel in Advanced Gastric Cancer Patients With D2 Surgery Combined With Hyperthermic Intraperitoneal Chemotherapy

Study Overview
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Brief Summary
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This study is a prospective, randomized, comparative clinical trial conducted by Wuhan Union Hospital and aim to compare the therapeutic effects of Lobaplatin and Paclitaxel in advanced gastric cancer patients with D2 surgery combined with hyperthermic intraperitoneal chemotherapy

Detailed Description
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Hyperthermic intraperitoneal chemotherapy (HIPEC) is traditionally used to treat peritoneal cancer combined with cytoreductive surgery (CRS). Further, there have been lots of randomized clinical trials assessing the efficacy of surgery + HIPEC for the treatment of locally advanced gastric cancer conducted. Nonetheless, to date, the kinds, doses, combinations of HIPEC drugs are not clearly been evaluate a criterion. Thus, This study aim to compare the efficacy of Lobaplatin and Paclitaxel in advanced gastric cancer patients with D2 surgery combined with HIPEC. We plan to recruit 231 patients and divide into 3 groups, 2 drug groups and 1 control groups, radomly. all patients with advanced gastric cancer receive D2 surgery + HIPEC + SOX/XELOX chemotherapy regimen. the mainly experimental variable is HIPEC drugs and three groups employ Lobaplatin, Paclitaxel and none respectively. the endpoints of study include peritoneal metastasis, overall survival, immune status and perioperative safety assessment.

Official Title
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Comparative Study on the Efficacy of Lobaplatin and Paclitaxel in the Treatment of Advanced Gastric Cancer Patients With D2 Surgery Combined With Hyperthermic Intraperitoneal Chemotherapy

Conditions
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Gastric Cancer, Chemotherapy Effect, Surgery, Metastasis, Survival

Intervention / Treatment
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* Drug: Paclitaxel
* Drug: Lobaplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: No chemoradiotherapy or other anti-tumor therapy before clinical trial performed; Aged 18-75 years; Male or non-pregnant or lactating women; Pathological diagnosis of gastric adenocarcinoma; Clinical diagnosis of T3 stage or above without distant metastasis and can be given D2 radical resection (AJCC Version 8, 2018); Normal function of major organs; Routine blood examinations meeting the following criteria: A. HB ≥ 90 g/L; B. ANC ≥ 1.5 x 10 9 /L; C. PLT ≥ 125 × 10 9 /L; Chemistry indexs meeting the following criteria: A. TBIL < 1.5ULN; B. ALT and AST < 2.5ULN; ALB > 30 g/L C. serum Cr ≤ 1.25 ULN or endogenous creatinine clearance > 50 ml/min (Cockcroft-Gault formula); ECOG score 0-1; Exclusion Criteria: A history of other malignant tumors within 5 years; Distant metastasis found during surgery; Allergic to paclitaxel, lobaplatin and other related chemotherapeutic drugs; Suffering from epilepsy or other mental illness, unable to control behavior; Inability to tolerate surgery due to severe cardiac, pulmonary and vascular disease; Pregnant or lactating women. Receiving anti-cancer drug therapy from other clinical trials.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: We divide patients into 3 groups randomly. Test group 1: D2 Surgery + HIPEC (paclitaxel) + SOX/XELOX regimen Test group 2: D2 Surgery + HIPEC (lobaplatin) + SOX/XELOX regimen Control group: D2 Surgery + HIPEC (no drug) + SOX/XELOX regimen
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug group 1<br>hyperthermic intraperitoneal chemotherapy (HIPEC) (with paclitaxel): Temperature Setting : 43 ± 1.0 ℃. Perfusion time: 60 min. Amount of perfusate: The perfusion fluid is based on the principle of filling the abdominal cavity and unobstructed circulation. Choice of perfusate: Normal saline. Drug selection and dose: Paclitaxel 75 mg/m2 . Treatment course: 2 times (the first time is after surgery, the second time is 48h after first time). | Drug: Paclitaxel<br>* Paclitaxel is used as drug for hyperthermic intraperitoneal chemotherapy. Choice of perfusate: Normal saline. Drug selection and dose: Paclitaxel 75 mg/m2 . Treatment course: 2 times (the first time is after surgery, the second time is 48h after first time).<br>|
| Experimental: Drug group 2<br>hyperthermic intraperitoneal chemotherapy (HIPEC) (with lobaplatin): Temperature Setting : 43 ± 1.0 ℃. Perfusion time: 60 min. Amount of perfusate: The perfusion fluid is based on the principle of filling the abdominal cavity and unobstructed circulation. Choice of perfusate: Normal saline. Drug selection and dose: lobaplatin 50 mg/m2 . Treatment course: 2 times (the first time is after surgery, the second time is 48h after first time). | Drug: Lobaplatin<br>* Lobaplatin is used as drug for hyperthermic intraperitoneal chemotherapy. Choice of perfusate: Normal saline. Drug selection and dose: lobaplatin 50 mg/m2 . Treatment course: 2 times (the first time is after surgery, the second time is 48h after first time).<br>|
| No Intervention: Control group<br>hyperthermic intraperitoneal therapy (HIPET) (no drug) : Temperature Setting : 43 ± 1.0 ℃. Perfusion time: 60 min. Amount of perfusate: The perfusion fluid is based on the principle of filling the abdominal cavity and unobstructed circulation. Choice of perfusate: Normal saline. Drug selection and dose: no drug. Treatment course: 2 times (the first time is after surgery, the second time is 48h after first time). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| peritoneal metastasis | peritoneal metastasis-free survival (pRFS) | 3-year | 
| overall survival | overall survival (OS) | 3-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with immunosuppression events as assessed by blood immunological indicators | Before and After Hyperthermic Intraperitoneal Chemotherapy, collect 5mL blood samples of patients for detecting immunological indicators such as CD3, CD4 and CD8 lymphocyte population; Interferon-γ; tumor necrosis factor (TNF)-α; interleukin-2, 4, 8, 10, etc | up to 4 weeks | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | postoperative adverse events (referring to CTCAE 5.0 [including blood routine, liver and kidney function, patient reaction to HIPEC, adverse events]) was analyzed | up to 4 weeks | 
| The positive rate of cancer cells of participants by exfoliative cytology examination | According to the positive rate of cancer cells measured in exfoliative cytology before and after HIPEC, the difference between the groups is analyzed. | 1 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lobaplatin, advanced gastric cancer, hyperthermic intraperitoneal chemotherapy, paclitaxel, prognosis