Treatment of Patients With Advanced Pancreatic Cancer After Gemcitabine Failure.

Instituto do Cancer do Estado de São Paulo

Status and phase: Completed; Phase 2

Conditions: Pancreatic Adenocarcinoma Advanced or Metastatic

Treatments: Drug: Metformin; Drug: Paclitaxel

Study type: Interventional

Funder types: Other

Identifiers

NCT01971034

NP 96/2010

Details and patient eligibility

About

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.

Enrollment: 41 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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41 participants in 1 patient group

Paclitaxel and Metformin

Experimental group

Treatment:

Drug: Paclitaxel

Drug: Metformin