Combination Chemotherapy With or Without Metformin Hydrochloride in Treating Patients With Metastatic Pancreatic Cancer (PACT-17)

• Overall survival [ Time Frame: every 14 days during therapy; every 3 months thereafter ] [ Designated as safety issue: No ]
  outpatient visit, phone interview
• Response rate [ Time Frame: every 2 months ] [ Designated as safety issue: No ]
  CT scan
• Toxicity [ Time Frame: every 2 weeks ] [ Designated as safety issue: Yes ]
  outpatient visit, laboratory findings

• Overall survival [ Designated as safety issue: No ]
• Response rate [ Designated as safety issue: No ]
• Duration of response [ Designated as safety issue: No ]
• Toxicity [ Designated as safety issue: Yes ]

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.

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.

• Drug: capecitabine
  1250 mg/mq days 1-28 every 4 weeks
  Other Name: XELODA
• Drug: cisplatin
  30 mg/mq on days 1 and 15 every 4 weeks
  Other Name: cisplatino TEVA
• Drug: epirubicin
  30 mg/mq on days 1 and 15 every 4 weeks
  Other Name: farmorubicina
• Drug: gemcitabine
  800 mg/mq on days 1 and 15 every 4 weeks
  Other Name: GEMZAR
• Drug: metformin
  2 g days 1-28 every 4 weeks
  Other Name: glucophage

• Experimental: PEXG regimen + metformin
  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
  Interventions:

  • Drug: capecitabine
  • Drug: cisplatin
  • Drug: epirubicin
  • Drug: gemcitabine
  • Drug: metformin
• Active Comparator: PEXG regimen
  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
  Interventions:

  • Drug: capecitabine
  • Drug: cisplatin
  • Drug: epirubicin
  • Drug: gemcitabine

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