Clinical trial NCT01477060 (phase 2, status: terminated)
Conditions: metastatic breast cancer
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: lapatinib, metformin
SMILES: CN(C1=CC2=NN(C)C(C)=C2C=C1)C1=CC=NC(NC2=CC=C(C)C(=C2)S(N)(=O)=O)=N1, CSCC[C@H](N)C(O)=O
Reason stopped: 
    the study was stopped due to insufficient accrual
  
Eligibility criteria:

        Inclusion Criteria:

          1. Female patients with a histologically or cytologically confirmed adenocarcinoma of the
             breast progressing from prior hormonal therapy

          2. Receptor positive disease (ER+ and/or PgR+)

          3. HER2 negative

          4. Pre- and post-menopausal status

          5. Documented disease progression after first-line hormone therapy

          6. Age ≥18 years.

          7. Measurable or evaluable metastatic disease

          8. Life expectancy > 3 months

          9. ECOG Performance Status < 1

         10. Adequate bone marrow, liver, and renal function as assessed by the following
             parameters:

               -  Hemoglobin > 9.0 g/dl

               -  Leucocytes count ≥ 3,000/mL

               -  Absolute neutrophil count (ANC) ≥ 1.500/mL

               -  Platelet count ≥ 100,000/mL

               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN
                  (≤ 5 x ULN for patients with liver involvement)

               -  Albumine and total bilirubin ≤ 1.5 x ULN

               -  Prothrombin Time (PT) < 70 %

               -  Serum creatinine < 1.4 mg/ml, creatinine clearance > 70 ml/min

         11. Normal Respiratory Function and Saturation level ≥ 90%

         12. New York Hearth Association (NYHA) Classification ≤ 2 and baseline left ventricular
             ejection fraction (LVEF)≥ 50%

         13. Patients must be willing and able to sign a written informed consent.

        Exclusion Criteria:

          1. Previous or concomitant treatment with lapatinib and/or metformin

          2. More than one line of prior hormone therapy for metastatic breast cancer.

          3. More than two lines of prior chemotherapy for metastatic breast cancer

          4. Unique location of disease local-regionally treated (surgery, radiotherapy , other)

          5. Disease progression not documented or less than 30%

          6. Metastatic disease defined as aggressive at investigator's judgement (e.g. visceral
             disease more than >1/3 of involved parenchyma, symptomatic disease requiring intensive
             supportive measures or therapies not allowed by protocol)

          7. Patients with brain metastasis

          8. Osteosclerotic bone metastasis as unique disease site

          9. Pathological tumor markers as unique sign of progressive disease

         10. Concomitant treatment with any other anticancer drugs (biphosphonates are permitted)

         11. Serious, not solved or unstable toxicity from previous treatment

         12. Diabetes mellitus Type I and Type II

         13. Renal insufficiency (creatinine ≥ 1.4 mg/ml)

         14. Malabsorption syndrome or diseases that significantly may alter gastroenteric
             functions

         15. Other serious illness or medical conditions judged by the investigator to be
             clinically significant that may adversely affect patient's participation in the trial
             or interfere with safety profile

         16. Active clinically significant or uncontrolled infections (bacterial or viral)

         17. Known history of unstable angina (angina symptoms at rest), cardiac ventricular
             arrhythmias clinically significant, myocardial infarction, stroke or congestive heart
             failure within 12 months prior to randomization

         18. History of lactic acidosis

         19. Evidence or symptoms of hepatic insufficiency

         20. Chronic alcoholism

         21. Concomitant treatment with amiodarone or any other agent that could interfere with
             study drugs

         22. Known or suspected hypersensitivity or allergy to lapatinib, metformin or used
             excipients

         23. Women who are pregnant or lactating

         24. History of previous cancer, unless at low risk of relapse per investigator's judgement