Study of Myocet Plus Cyclophosphamide Plus Metformin Versus Myocet Plus Cyclophosphamide in First Line Treatment of HER2 Negative Metastatic Breast Cancer Patients
Overview[ - collapse ][ - ]
Purpose | MULTICENTER, RANDOMIZED, COMPARATIVE STUDY OF MYOCET PLUS CYCLOPHOSPHAMIDE PLUS METFORMIN VERSUS MYOCET PLUS CYCLOPHOSPHAMIDE IN FIRST LINE TREATMENT OF HER2 NEGATIVE METASTATIC BREAST CANCER PATIENTS. The aim of this study is to determine if the addition of metformin to the regime Myocet / Cyclophosphamide improves disease-free survival in patients with HER2-negative metastatic breast cancer. The primary objective is the evaluation of the clinical efficacy of the combination of Myocet / Cyclophosphamide plus Metformin compared to treatment with only Myocet / Cyclophosphamide, in terms of progression-free survival (PFS). Clinical secondary objectives are: - Objective response rate - Overall survival - Tolerability - Progression-free survival, objective response rate and overall survival according to Homa Index levels. Secondary biological endpoint is the characterization of the metabolic profile of patients (sensitivity in insulin levels). Treatment Arm A (experimental treatment): Metformin 1000 mg, 2 times daily per os*. Myocet 60 mg/m2, intravenous infusion, on day 1, every 21 days Cyclophosphamide 600 mg/m2, intravenous infusion, at day 1 every 21 days. * During cycle 1, patients will assume only metformin from day 1 to day 13 and will begin chemotherapy from day 14. From day 1 to day 3, patients will assume Metformin 1000 mg once a day. Starting from day 4 patients will assume Metformin 1000 mg 2 times a day. Arm B (standard treatment): Myocet 60 mg/m2, intravenous infusion, on day 1, every 21 days Cyclophosphamide 600 mg/m2, intravenous infusion, on day 1, every 21 days Chemotherapy will be performed for 8 cycles. The treatment will be continued until progression of disease. Statistical Considerations: In this randomized phase II study, the sample size was calculated basing on the primary end-point (PFS) and assuming an error α = 10% (2-tailed) with a power of 80%. To find an advantage of 4 months of median time to progression (6 months in the control arm B and 10 months in the experimental arm A) will be recruited 112 patients (98 events) for a period of 24 months and will be considered further 12-month of follow-up. The primary analysis of the study will be conducted in accordance with the "intention to treat" principle, the secondary analysis will be conducted in the "per protocol" population. |
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Condition | HER2-negative Metastatic Breast Cancer Patients |
Intervention | Drug: Metformin + Myocet + Cyclophosphamide Drug: Myocet + Cyclophosphamide |
Phase | Phase 2 |
Sponsor | Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori |
Responsible Party | Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori |
ClinicalTrials.gov Identifier | NCT01885013 |
First Received | June 19, 2013 |
Last Updated | June 21, 2013 |
Last verified | June 2013 |
Tracking Information[ + expand ][ + ]
First Received Date | June 19, 2013 |
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Last Updated Date | June 21, 2013 |
Start Date | September 2010 |
Estimated Primary Completion Date | April 2014 |
Current Primary Outcome Measures | progression-free survival (PFS) [Time Frame: 42 months] [Designated as safety issue: No]Clinical efficacy of the combination of Myocet / Cyclophosphamide plus Metformin compared to treatment with only Myocet / Cyclophosphamide, in terms of progression-free survival (PFS) |
Current Secondary Outcome Measures |
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Descriptive Information[ + expand ][ + ]
Brief Title | Study of Myocet Plus Cyclophosphamide Plus Metformin Versus Myocet Plus Cyclophosphamide in First Line Treatment of HER2 Negative Metastatic Breast Cancer Patients |
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Official Title | MYME: PHASE II COMPARATIVE STUDY OF MYOCET PLUS CYCLOPHOSPHAMIDE PLUS METFORMIN VERSUS MYOCET PLUS CYCLOPHOSPHAMIDE IN FIRST LINE TREATMENT OF HER2 NEGATIVE METASTATIC BREAST CANCER PATIENTS |
Brief Summary | MULTICENTER, RANDOMIZED, COMPARATIVE STUDY OF MYOCET PLUS CYCLOPHOSPHAMIDE PLUS METFORMIN VERSUS MYOCET PLUS CYCLOPHOSPHAMIDE IN FIRST LINE TREATMENT OF HER2 NEGATIVE METASTATIC BREAST CANCER PATIENTS. The aim of this study is to determine if the addition of metformin to the regime Myocet / Cyclophosphamide improves disease-free survival in patients with HER2-negative metastatic breast cancer. The primary objective is the evaluation of the clinical efficacy of the combination of Myocet / Cyclophosphamide plus Metformin compared to treatment with only Myocet / Cyclophosphamide, in terms of progression-free survival (PFS). Clinical secondary objectives are: - Objective response rate - Overall survival - Tolerability - Progression-free survival, objective response rate and overall survival according to Homa Index levels. Secondary biological endpoint is the characterization of the metabolic profile of patients (sensitivity in insulin levels). Treatment Arm A (experimental treatment): Metformin 1000 mg, 2 times daily per os*. Myocet 60 mg/m2, intravenous infusion, on day 1, every 21 days Cyclophosphamide 600 mg/m2, intravenous infusion, at day 1 every 21 days. * During cycle 1, patients will assume only metformin from day 1 to day 13 and will begin chemotherapy from day 14. From day 1 to day 3, patients will assume Metformin 1000 mg once a day. Starting from day 4 patients will assume Metformin 1000 mg 2 times a day. Arm B (standard treatment): Myocet 60 mg/m2, intravenous infusion, on day 1, every 21 days Cyclophosphamide 600 mg/m2, intravenous infusion, on day 1, every 21 days Chemotherapy will be performed for 8 cycles. The treatment will be continued until progression of disease. Statistical Considerations: In this randomized phase II study, the sample size was calculated basing on the primary end-point (PFS) and assuming an error α = 10% (2-tailed) with a power of 80%. To find an advantage of 4 months of median time to progression (6 months in the control arm B and 10 months in the experimental arm A) will be recruited 112 patients (98 events) for a period of 24 months and will be considered further 12-month of follow-up. The primary analysis of the study will be conducted in accordance with the "intention to treat" principle, the secondary analysis will be conducted in the "per protocol" population. |
Detailed Description | Not Provided |
Study Type | Interventional |
Study Phase | Phase 2 |
Study Design | Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment |
Condition | HER2-negative Metastatic Breast Cancer Patients |
Intervention | Drug: Metformin + Myocet + Cyclophosphamide Drug: Myocet + Cyclophosphamide |
Study Arm (s) |
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Recruitment Information[ + expand ][ + ]
Recruitment Status | Recruiting |
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Estimated Enrollment | 112 |
Estimated Completion Date | April 2014 |
Estimated Primary Completion Date | April 2014 |
Eligibility Criteria | Inclusion Criteria: 1. Patients must have histologically or cytologically confirmed breast cancer 2. Metastatic disease 3. HER2 negative disease, as measured by IHC or FISH 4. Non endocrine responsive disease (negative hormonal status or failure of endocrine therapy for MBC) 5. Patients with measurable and/or non-measurable disease according to RECIST Criteria (Version 1.1) 6. Homa Index calculated according to Matthews' formula 7. Prior endocrine therapy is allowed, in the adjuvant and/or metastatic setting 8. Prior chemotherapy is allowed, only in adjuvant setting, provided it is terminated at least 12 months before study entry. Adjuvant anthracyclines are allowed if prior cumulative dose does not exceed 360 mg/m2 in case of epirubicin and 280 mg/m2 in case of doxorubicin. Adjuvant taxanes are allowed. 9. Age 18-75 years 10. Life expectancy of greater than 3 months 11. ECOG performance status <2 12. Patients must have normal organ and marrow function: - leukocytes >=3,000/μL - absolute neutrophil count >=1,500/μL - platelets >=100,000/μL - total bilirubin within normal institutional limits - AST(SGOT)/ALT(SGPT) <=1.5 X institutional upper limit of normal - creatinine within normal institutional limits 13. Adequate cardiac function, i.e. left ventricular ejection fraction (LVEF)>= 50% 14. The effects of liposomal doxorubicin on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because anthracyclines as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. All women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the start of study medication. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. 15. Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: 1. Known diabetes (type 1 or 2) 2. Currently on metformin, sulfonylureas, thiazolidenediones or insulin for any reason (these drugs alter insulin levels) 3. Current or previous congestive heart failure, renal failure or liver failure; history of acidosis of any type; habitual intake of 3 or more alcoholic beverages per day 4. Creatinine above upper limit of normal for institution, AST above 1.5 times upper limit or normal for institution (to reduce risk of lactic acidosis) 5. Hypersensitivity or allergy to metformin 6. Participation in another clinical trial with any investigational agents within 30 days prior to study screening 7. Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events 8. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Myocet or other agents used in the study 9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. |
Gender | Female |
Ages | 18 Years |
Accepts Healthy Volunteers | No |
Contacts | Contact: Oriana Nanni, PhD +390543739266 o.nanni@irst.emr.it |
Location Countries | Italy |
Administrative Information[ + expand ][ + ]
NCT Number | NCT01885013 |
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Other Study ID Numbers | IRST174.04 |
Has Data Monitoring Committee | No |
Information Provided By | Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori |
Study Sponsor | Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori |
Collaborators | Not Provided |
Investigators | Not Provided |
Verification Date | June 2013 |
Locations[ + expand ][ + ]
P.O. M. Bufalini | Cesena, FC, Italy Contact: Marina Faedi, MDPrincipal Investigator: Marina Faedi, MD Recruiting |
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Irccs Irst | Meldola (FC), FC, Italy, 47014 Contact: Oriana Nanni, PhD | +39 0543739266 | o.nanni@irst.emr.itPrincipal Investigator: Dino Amadori, Prof. Recruiting |
Ospedale Civile degli Infermi | Faenza, RA, Italy Contact: Stefano Tamberi, MDPrincipal Investigator: Stefano Tamberi, MD Recruiting |
Ospedale Umberto I | Lugo, RA, Italy Contact: Giorgio Cruciani, MDPrincipal Investigator: Giorgio Cruciani, MD Recruiting |
Ospedale Civile Santa Maria delle Croci | Ravenna, RA, Italy Contact: Giorgio Cruciani, MDPrincipal Investigator: Giorgio Cruciani, MD Recruiting |
ULSS n.8 Asolo Ospedale di Castelfranco | Asolo, Italy Contact: Paolo Manente, MDPrincipal Investigator: Paolo Manente, MD Recruiting |
Centro di Riferimento Oncologico CRO | Aviano, Italy Contact: Andrea Freschi, MDPrincipal Investigator: Andrea Freschi, MD Recruiting |
Ospedale S.Martino | Belluno, Italy Contact: Petros Giovanis, MDPrincipal Investigator: Petros Giovanis, MD Recruiting |
Azienda Ospedaliera "Antonio Cardarelli" | Campobasso, Italy Contact: Francesco Carrozza, MDPrincipal Investigator: Francesco Carrozza, MD Recruiting |
P.O. "SS. Annunziata" | Chieti, Italy Contact: Stefano Iacobelli, MDPrincipal Investigator: Stefano Iacobelli, MD Recruiting |
Presidio Ospedaliero E. Profili | Fabriano, Italy Contact: Rosa Rita Silva, MDPrincipal Investigator: Rosa Rita Silva, MD Recruiting |
E.O. Galliera | Genova, Italy Contact: Alessandra Gennari, MDPrincipal Investigator: Alessandra Gennari, MD Recruiting |
Ospedale di Guastalla | Guastalla, Italy Contact: Laura Scaltriti, MDPrincipal Investigator: Laura Scaltriti, MD Recruiting |
Azienda per i Servizi Sanitari n.5 "Bassa Friulana" | Latisana, Italy Contact: Aldo Iop, MDPrincipal Investigator: Aldo Iop, MD Recruiting |
Presidio Ospedaliero "Vito Fazzi" | Lecce, Italy Contact: Mariangela Ciccarese, MDPrincipal Investigator: Mariangela Ciccarese, MD Recruiting |
ULSS n.13 di Mirano | Mirano, Italy Contact: Mario Bari, MDPrincipal Investigator: Mario Bari, MD Recruiting |
Arcispedale S. Maria Nuova | Modena, Italy Contact: Massimo Federico, MDPrincipal Investigator: Massimo Federico, MD Recruiting |
Azienda Ospedaliera S. Salvatore di Pesaro | Pesaro, Italy Contact: Virginia Casadei, MDPrincipal Investigator: Virginia Casadei, MD Recruiting |
Ospedale S. Spirito | Pescara, Italy Contact: Marco Lombardo, MDPrincipal Investigator: Marco Lombardo, MD Recruiting |
Ospedale Civile di Piacenza | Piacenza, Italy Contact: Luigi Cavanna, MDPrincipal Investigator: Luigi Cavanna, MD Recruiting |
Azienda Ospedaliera Santa Maria degli Angeli | Pordenone, Italy Contact: Silvana Saracchini, MDPrincipal Investigator: Silvana Saracchini, MD Recruiting |
Arcispedale S. Maria Nuova | Reggio E,milia, Italy Contact: Corrado Boni, MDPrincipal Investigator: Corrado Boni, MD Recruiting |
Ospedale Civile degli Infermi | Rimini, Italy Contact: Lorenzo Gianni, MDPrincipal Investigator: Lorenzo Gianni, MD Recruiting |
IRCCS Centro di riferimento Oncologico di Basilicata di Rionero in Vulture | Rionero in Vulture, Italy Contact: Michele Aieta, MDPrincipal Investigator: Michele Aieta, MD Recruiting |
Ospedale Nuovo Regina Margherita | Roma, Italy Contact: Germano Zampa, MDPrincipal Investigator: Germano Zampa, MD Recruiting |