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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. - MYME

Conditions
HER2 negative metastatic breast cancer patients
MedDRA version: 9.1Level: LLTClassification code 10055113
Registration Number
EUCTR2009-014662-26-IT
Lead Sponsor
ISTITUTO SCIENTIFICO ROMAGNOLO PER LO STUDIO E LA CURA DEI TUMORI
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
Female
Target Recruitment
Not specified
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 bilirubinwithin normal institutional limits
-AST(SGOT)/ALT(SGPT)≤1.5 X institutional upper limit of normal
-creatininewithin 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: 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.;Secondary Objective: Objective Response Rates and Overall Survival of Myocet/Cyclophosphamide/Metformin as compared with Myocet/Cyclophosphamide<br>Safety<br>Evaluation of patient metabolic profile (metabolic syndrome);Primary end point(s): progression free survival
Secondary Outcome Measures
NameTimeMethod
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