Metformin in Combined With Cisplatin Plus Paclitaxel With Advanced Esophageal Squamous Cell Carcinoma (ECMTPneo)

Study Overview
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Brief Summary
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This is an open-label phase II trial investigating the effect of metformin in combined with cisplatin plus paclitaxel as neoadjuvant therapy with advanced esophageal squamous cell carcinoma.

Detailed Description
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In this prospective phase II study, eligible patients are received cisplatin plus paclitaxel for 2-4 cycles combined with metformin orally. The investigators aim to compare the tumor metabolic pathway and tumor microenvironment of pre-chemotherapy endoscopic biopsy samples and post-chemotherapy surgical resection samples.

Official Title
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Metformin in Combined With Cisplatin Plus Paclitaxel as Neoadjuvant Therapy With Advanced Esophageal Squamous Cell Carcinoma (ESCC)

Conditions
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Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: metformin and chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Having signed informed consent. Age 18 to 70 years old Histologically confirmed esophageal squamous carcinoma Computed tomography (CT) or magnetic resonance imaging (MRI) confirmed advanced ESCC which need neoadjuvant chemotherapy before surgical resection. Measurable disease according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria(diameter of the lesion should be more than 10mm by spiral CT or MRI, more than 20mm by common CT, the date of image should be less than 21 days before enrollment) Life expectancy of ≥3 month Eastern Cooperative Oncology Group (ECOG) 0-1 Body Mass Index (BMI) ≥18.5kg/m2 WBC>3,000/mm3, absolute neutrophil count ≥1500/mm3, platelet>100,000/mm3, Hb>9g/dl，Bilirubin level < 1.5 times ULN，Serum creatinine <1.5 times ULN，ALT and AST<2.5 times ULN ，AKP < 2.5 times ULN ，(≤5 times ULN in patients with liver metastases)(within 7 days before enrollment) No sever complication, such as active gastrointestinal bleeding, perforation, jaundice, obstruction, non-cancerous fever>38℃. Good compliance Exclusion Criteria: Have used metformin or biguanide in the past Contraindications of metformin Unable to take metformin orally because of esophageal stenosis Currently receiving other effective regimens Previous anticipate other clinical trial within 4 weeks before entering this study No measurable lesions, eg. pleural fluid and ascites\ Only with other previous malignancy within 5 year, except non-melanoma skin cancer and cervical carcinoma in situ Heart failure or other sever organ dysfunction, eg. coronary artery disease, myocardial infarction within the last 6 months only Brain or bone metastasis Mentally abnormal or disable cognition,including central nervous system (CNS) metastasis HIV infection, active hepatitis B or hepatitis C Unstable systemic diseases such as poorly controlled diabetes Interstitial lung disease, such as interstitial pneumonia, pulmonary fibrosis, or evidence of interstitial lung disease showed in X-ray/CT Known hypersensitivity to study drugs Pregnancy or lactation period

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: metformin and chemotherapy<br> | Drug: metformin and chemotherapy<br>* Drug: Metformin Metformin is orally administered as 500mg bid for 7 days and escaladed to 500mg tid if adverse events are tolerated. Drug: Cisplatin Cisplatin is given at 75mg/m2 intravenously on day 1 of each 21 day cycle. Drug: Paclitaxel Paclitaxel is given at 175mg/m2 intravenously on day 1 of each 21 day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor metabolic pathway | To compare the changes of tumor metabolic pathway of pre-chemotherapy endoscopic biopsy samples and post-chemotherapy surgical resection samples | Through study completion, an average of 1 year | 
| Tumor microenvironment | To compare the changes of tumor microenvironment of pre-chemotherapy endoscopic biopsy samples and post-chemotherapy surgical resection samples | Through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of pathologic complete response（pCR） | Rate of pathologic complete response | Through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Esophageal Squamous Cell Carcinoma, Neoadjuvant Therapy, Metformin, Cisplatin, Paclitaxel