Modulation of response to hormonal therapy with lapatinib and/or metformin in patients with HER2-negative, ER and/or PgR positive metastatic breast cancer with progressive disease after first-line hormonal therapy

• Conditions: Female patients with HER2-negative, ER and/or PgR positive breast cancer in progression after first-line hormonal therapy; MedDRA version: 14.1Level: SOCClassification code 10038604Term: Reproductive system and breast disordersSystem Organ Class: 10038604 - Reproductive system and breast disorders; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-000155-16-IT
• Lead Sponsor: FONDAZIONE MICHELANGELO - AVANZAMENTO DELLO STUDIO E CURA DEI TUMORI

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-03-20
• Last Update Posted: 12 May 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: Not specified

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 according to RECIST Criteria 1.1 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/mm3 Absolute neutrophil count (ANC)>= 1,500/mm3 Platelet count >= 100,000/mm3 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
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 144
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 24

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 parenchima, 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 eccipients 23. Women who are pregnant or lactating 24. History of previous cancer, unless at low risk of relapse per investigator’s judgement

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the rate of patients free from disease progression at 3 months from randomization;Secondary Objective: To assess the overall response rate To assess the duration of response To assess 3-years overall survival rate To assess tolerability of each proposed treatment;Primary end point(s): To assess how many patients, after 3 months of therapy, are free of progressive disease;Timepoint(s) of evaluation of this end point: After three months of treatment

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): To assess the overall response rate To assess the duration of response in patients who achieved e partial or complete remission To assess 3-years overall survival rate To assess tolerability of each proposed treatment;Timepoint(s) of evaluation of this end point: After 3 years from the start of treatment