Clinical trial NCT03833466: Metformin in Combined With Cisplatin Plus Paclitaxel With Advanced Esophageal Squamous Cell Carcinoma (ECMTPneo)
Official title: Metformin in Combined With Cisplatin Plus Paclitaxel as Neoadjuvant Therapy With Advanced Esophageal Squamous Cell Carcinoma (ESCC)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Esophageal Squamous Cell Carcinoma
Keywords: Advanced Esophageal Squamous Cell Carcinoma
Neoadjuvant Therapy
Metformin
Cisplatin
Paclitaxel
Lead sponsor: Peking University
Sponsor class: OTHER
First posted: 2019-02-07
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Tumor metabolic pathway
timeFrame: Through study completion, an average of 1 year
measure: Tumor microenvironment
timeFrame: Through study completion, an average of 1 year
Secondary outcomes:
measure: Rate of pathologic complete response（pCR）
timeFrame: Through study completion, an average of 1 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Universtiy Cancer Hospital
state: Beijing
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Zhihao Lu, MD
role: PRINCIPAL_INVESTIGATOR
References: