Treatment of Patients With Advanced Pancreatic Cancer After Gemcitabine Failure.

A Prospective Study to Evaluate the Combination of Metformin With Paclitaxel in the Treatment of Patients With Advanced Pancreatic Cancer After Gemcitabine Failure.

In Brazil pancreatic adenocarcinoma represents 2% of tumors, and 4% mortality being an uncommon disease, however very aggressive.Only 20% of cases are indicated for curative surgery, of which only 20% are alive within 5 years. For locally, advanced or metastatic disease, since 1997, single chemotherapy with gemcitabine is the standard treatment for first line, with survival around 6 months approximately.There is no standard treatment regimen for second-line, however Paclitaxel demonstrated effect on second-line phase II study. Metformin is an oral hypoglycemic drug used for treatment of diabetes mellitus. There is a growing number of preclinical studies which show antitumor effect against pancreatic adenocarcinoma, probably due to the effect of anti-insulin growth factor (IGF-1). This study will add metformin to standard treatment for second line of locally advanced or metastatic pancreatic adenocarcinoma in ICESP previously treated with gemcitabine. The objective is to evaluate whether metformin improves the efficacy of the standard treatment with paclitaxel by clinical and radiological evaluation.

Study Overview

• Status: Completed
• Conditions: Pancreatic Adenocarcinoma Advanced or Metastatic
• Intervention / Treatment: Drug: Paclitaxel; Drug: Metformin

• Study Type: Interventional
• Enrollment (Anticipated): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Sao Paulo, SP, Brazil, 01246000
      • ICESP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pancreatic advanced or metastatic adenocarcinoma histologically confirmed.
• Previously treatment with gemcitabine as adjuvant or metastatic disease.
• Clinical or radiological evidence of disease progression, determined by physician. Is not mandatory RECIST (Response Evaluation Criteria in Solid Tumors) evaluation to determine the progression of disease before the study inclusion.
• Patient with intolerance to gemcitabine, even without disease progression, are also eligible.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
• At least 10 weeks of life expectation.

• Adequate organ function defined as:

  • Serum AST (aspartate aminotransferase) and ALT (alanine aminotransferase)≤ 2.5 × ULN (upper normal limit)
  • Total Bilirubin ≤ 2,0 x ULN
  • Absolute neutrophil count ≥ 1,500/ mm3
  • Platelets ≥100.000/ mm3
  • Hemoglobin ≥ 8,0 g/dl
  • Serum Creatinine ≤ 1,5 ULN and clearance of creatinine estimated (Cockcroft- Gault) ≥ 50 ml/min
• Signed written informed consent.

Exclusion Criteria:

• Major surgical procedure within 4 weeks of the beginning of the treatment.
• History of serious clinical or psychiatric disease.
• Symptomatic hypoglycemia at the screening visit.
• Target lesion radiotherapy within 4 weeks of the beginning of the treatment.
• Treatment with any anti-cancer investigational drug.
• Treatment with any IGF-I or IGFR-I
• Treatment with metformin within 12 months prior to commencing study treatment
• For female patients, current pregnancy and/or lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Paclitaxel and Metformin	Drug: Paclitaxel; 80 mg/m2, IV, Day 1, Day 8 and Day 15.; Drug: Metformin; 850mg, PO, every 8 hours, daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiologic control of disease	The radiologic image will be analyzed by RECIST 1.0 criteria.	Every 8 weeks from the date of first dose of treatment until disease progression.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to progression.	Thorax and abdominal computerized tomography and Ca 19.9 tumor marker dosage every 8 weeks until disease progression.	Every 8 weeks from the date of first dose of treatment until disease progression.
To estimate the biochemical response through the measurement of serum CA19.9 levels.		From the date of first dose of treatment until disease progression.
To evaluate the clinical benefits	Will be evaluate: ECOG; Treatment with opioids; Pain; Weight	Every 4 weeks during the treatment period until disease progression.

Collaborators and Investigators

• Sponsor: Instituto do Cancer do Estado de São Paulo
• Investigators: Principal Investigator: Rachel SP Riechelmann, MD, Instituto do Cancer do Estado de Sao Paulo

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: September 6, 2013
• First Submitted That Met QC Criteria: October 22, 2013
• First Posted (Estimate): October 28, 2013

Study Record Updates

• Last Update Posted (Estimate): May 16, 2014
• Last Update Submitted That Met QC Criteria: May 14, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Metformin
• Other Study ID Numbers: NP 96/2010