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

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

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.

Study Overview

• Status: Terminated
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: capecitabine; Drug: cisplatin; Drug: epirubicin; Drug: gemcitabine; Drug: metformin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20132
    • Istituto Scientifico H. San Raffaele

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	Drug: capecitabine; 1250 mg/mq days 1-28 every 4 weeks; Other Names: XELODA; Drug: cisplatin; 30 mg/mq on days 1 and 15 every 4 weeks; Other Names: cisplatino TEVA; Drug: epirubicin; 30 mg/mq on days 1 and 15 every 4 weeks; Other Names: farmorubicina; Drug: gemcitabine; 800 mg/mq on days 1 and 15 every 4 weeks; Other Names: GEMZAR; Drug: metformin; 2 g days 1-28 every 4 weeks; Other Names: glucophage
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	Drug: capecitabine; 1250 mg/mq days 1-28 every 4 weeks; Other Names: XELODA; Drug: cisplatin; 30 mg/mq on days 1 and 15 every 4 weeks; Other Names: cisplatino TEVA; Drug: epirubicin; 30 mg/mq on days 1 and 15 every 4 weeks; Other Names: farmorubicina; Drug: gemcitabine; 800 mg/mq on days 1 and 15 every 4 weeks; Other Names: GEMZAR

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: IRCCS San Raffaele

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (ACTUAL): December 1, 2014
• Study Completion (ACTUAL): April 1, 2015

Study Registration Dates

• First Submitted: July 21, 2010
• First Submitted That Met QC Criteria: July 21, 2010
• First Posted (ESTIMATE): July 22, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): April 24, 2015
• Last Update Submitted That Met QC Criteria: April 23, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: adenocarcinoma of the pancreas; stage IV pancreatic cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Gemcitabine; Cisplatin; Capecitabine; Epirubicin; Metformin
• Other Study ID Numbers: CDR0000681691; PACT-17 (OTHER: IRCCS San Raffaele); 2010-020979-23 (EUDRACT_NUMBER)