Combination Chemotherapy With or Without Metformin Hydrochloride in Treating Patients With Metastatic Pancreatic Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Metformin hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known if combination chemotherapy is more effective with or without metformin hydrochloride in treating patients with metastatic pancreatic cancer. PURPOSE: This randomized phase II trial is studying giving cisplatin, epirubicin hydrochloride, capecitabine, and gemcitabine hydrochloride together with metformin hydrochloride to see how well it works compared to cisplatin, epirubicin hydrochloride, capecitabine, and gemcitabine hydrochloride alone in treating patients with metastatic pancreatic cancer.

Detailed Description
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OBJECTIVES: Primary To assess the therapeutic activity of chemotherapy comprising cisplatin, epirubicin hydrochloride, capecitabine, and gemcitabine hydrochloride with versus without metformin hydrochloride in terms of 6-month progression-free survival in patients with metastatic pancreatic cancer. Secondary To assess the overall survival of patients treated with this regimen. To assess the response rate in patients treated with this regimen. To assess the duration of response in patients treated with this regimen. To assess the toxicity in patients treated with this regimen. OUTLINE: Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive cisplatin, epirubicin hydrochloride, and gemcitabine hydrochloride on days 1 and 15. Patients will also receive capecitabine and metformin hydrochloride on days 1-28. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive cisplatin, epirubicin hydrochloride, gemcitabine hydrochloride, and capecitabine as in arm I. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Official Title
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A Randomized Phase II Study of Chemotherapy ± Metformin in Metastatic Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: capecitabine
* Drug: cisplatin
* Drug: epirubicin
* Drug: gemcitabine
* Drug: metformin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed pancreatic adenocarcinoma Metastatic (stage IV) disease Measurable disease No symptomatic brain metastases PATIENT CHARACTERISTICS: Karnofsky performance status 60-100% Not pregnant or nursing Adequate bone marrow, liver and kidney function No previous or concurrent malignancies at other sites except for surgically cured carcinoma in-situ of the cervix, basal cell or squamous cell carcinoma of the skin, or other neoplasms without evidence of disease within the past 5 years No multiple severe diseases which would compromise safety (i.e., cardiac failure, previous myocardial infarction within the past 4 months, cardiac arrhythmia, or history of psychiatric disabilities) No alcohol abuse PRIOR CONCURRENT THERAPY: No prior chemotherapy or metformin No other concurrent experimental drugs

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEXG regimen + metformin<br>cisplatin and epirubicin at 30 mg/mq on days 1 and 15, capecitabine at 1250 mg/mq days 1-28, gemcitabine at 800 mg/mq on days 1 and 15, Metformin at 2 g days 1-28 | Drug: capecitabine<br>* 1250 mg/mq days 1-28 every 4 weeks<br>* Other names: XELODA;Drug: cisplatin<br>* 30 mg/mq on days 1 and 15 every 4 weeks<br>* Other names: cisplatino TEVA;Drug: epirubicin<br>* 30 mg/mq on days 1 and 15 every 4 weeks<br>* Other names: farmorubicina;Drug: gemcitabine<br>* 800 mg/mq on days 1 and 15 every 4 weeks<br>* Other names: GEMZAR;Drug: metformin<br>* 2 g days 1-28 every 4 weeks<br>* Other names: glucophage;|
| Active Comparator: PEXG regimen<br>cisplatin and epirubicin at 30 mg/mQ on days 1 and 15, capecitabine at 1250 mg/mq days 1-28, gemcitabine at 800 mg/mq on days 1 and 15 | Drug: capecitabine<br>* 1250 mg/mq days 1-28 every 4 weeks<br>* Other names: XELODA;Drug: cisplatin<br>* 30 mg/mq on days 1 and 15 every 4 weeks<br>* Other names: cisplatino TEVA;Drug: epirubicin<br>* 30 mg/mq on days 1 and 15 every 4 weeks<br>* Other names: farmorubicina;Drug: gemcitabine<br>* 800 mg/mq on days 1 and 15 every 4 weeks<br>* Other names: GEMZAR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival at 6 months | CT scan | every 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | outpatient visit, phone interview | every 14 days during therapy; every 3 months thereafter | 
| Response rate | CT scan | every 2 months | 
| Toxicity | outpatient visit, laboratory findings | every 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the pancreas, stage IV pancreatic cancer