Treatment of Patients With Advanced Pancreatic Cancer After Gemcitabine Failure.

Study Overview
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Brief Summary
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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.

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

Conditions
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Pancreatic Adenocarcinoma Advanced or Metastatic

Intervention / Treatment
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* Drug: Paclitaxel
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paclitaxel and Metformin<br> | Drug: Paclitaxel<br>* 80 mg/m2, IV, Day 1, Day 8 and Day 15.<br>Drug: Metformin<br>* 850mg, PO, every 8 hours, daily.<br>|

What is the study measuring?
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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. |