E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HER2 negative metastatic breast cancer patients |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055113 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to evaluate the efficacy of the combination of Myocet plus Cyclophosphamide plus metformin as compared to Myocet plus Cyclophosphamide in HER2 negative metastatic breast cancer patients, in terms of progression free survival. |
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E.2.2 | Secondary objectives of the trial |
Objective Response Rates and Overall Survival of Myocet/Cyclophosphamide/Metformin as compared with Myocet/Cyclophosphamide Safety Evaluation of patient metabolic profile (metabolic syndrome) |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
ALTRI SOTTOSTUDI: Valutazione delle cellule tumorali circolanti
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E.3 | Principal inclusion criteria |
Patients must have histologically or cytologically confirmed breast cancer Metastatic disease HER2 negative disease, as measured by IHC or FISH Non endocrine responsive disease (negative hormonal status or failure of endocrine therapy for MBC) Insulin resistance, as measured by HOMA Index > >.8 (See Appendix A) Presence of measurable disease. (See section 9.2 for the evaluation of measurable disease). Prior endocrine therapy is allowed, in the adjuvant and/or metastatic setting Prior adjuvant chemotherapy is allowed provided it is terminated at least 12 months before study entry. Adjuvant anthracyclines are allowed if prior cumulative dose does not exceed 300 mg/m2 in case of epirubicin and 240 mg/m2 in case of doxorubicin. Adjuvant taxanes are allowed. Age 18-75 years Life expectancy of greater than 3 months ECOG performance status <2 (See Appendix B) Patients must have normal organ and marrow function as defined below: - leukocytes >3,000/L - absolute neutrophil count >1,500/L - platelets >100,000/L - total bilirubin within normal institutional limits - AST(SGOT)/ALT(SGPT) ≤1.5 X institutional upper limit of normal - creatinine within normal institutional limits Adequate cardiac function, i.e. left ventricular ejection fraction (LVEF) ≥ 50%. 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. Ability to understand and the willingness to sign a written informed consent document. |
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E.4 | Principal exclusion criteria |
Known diabetes (type 1 or 2) Currently on metformin, sulfonylureas, thiazolidenediones or insulin for any reason (these drugs alter insulin levels) 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 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) Hypersensitivity or allergy to metformin Participation in another clinical trial with any investigational agents within 30 days prior to study screening. 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. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Myocet or other agents used in the study. 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
progression free survival |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 30 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |