NCT01885013

Brief Summary

This is a phase II comparative randomized clinical trial. Eligible patients will be randomized (1:1) to: Arm A: Myocet plus Cyclofosfamide plus Metformin Arm B: Myocet plus Cyclofosfamide 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
126

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Sep 2010

Longer than P75 for phase_2

Geographic Reach
1 country

25 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2010

Completed
2.8 years until next milestone

First Submitted

Initial submission to the registry

June 19, 2013

Completed
5 days until next milestone

First Posted

Study publicly available on registry

June 24, 2013

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2015

Completed
Last Updated

January 1, 2016

Status Verified

December 1, 2015

Enrollment Period

4.7 years

First QC Date

June 19, 2013

Last Update Submit

December 31, 2015

Conditions

Keywords

HER2 negativemetastatic breast cancernon endocrine responsive disease

Outcome Measures

Primary Outcomes (1)

  • progression-free survival (PFS)

    Clinical efficacy of the combination of Myocet / Cyclophosphamide plus Metformin compared to treatment with only Myocet / Cyclophosphamide, in terms of progression-free survival (PFS)

    42 months

Secondary Outcomes (6)

  • Objective response rate

    42 months

  • Overall survival

    42 months

  • Progression free survival as function of Homa Index levels

    42 months

  • objective response rate as function of Homa Index levels

    42 months

  • overall survival as function of Homa Index levels

    42 months

  • +1 more secondary outcomes

Study Arms (2)

Metformin + Myocet + Cyclophosphamide

EXPERIMENTAL

arm A : 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.

Drug: Metformin + Myocet + Cyclophosphamide

Myocet + Cyclophosphamide

ACTIVE COMPARATOR

arm B : Myocet 60 mg/m2, intravenous infusion, on day 1, every 21 days Cyclophosphamide 600 mg/m2, intravenous infusion, on day 1, every 21 days

Drug: Myocet + Cyclophosphamide

Interventions

Metformin + Myocet + Cyclophosphamide: Metformin 1000 mg, 2 times daily per os\*. Myocet 60 mg/m2, intravenous infusion, on day 1, every 21 days Chemotherapy will be performed for 8 cycles 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.

Also known as: metformin, myocet, cyclofosfamide
Metformin + Myocet + Cyclophosphamide

Myocet + Cyclophosphamide: 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

Also known as: myocet, cyclofosfamide
Myocet + Cyclophosphamide

Eligibility Criteria

Age18 Years - 75 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)
  • Patients with measurable and/or non-measurable disease according to RECIST Criteria (Version 1.1)
  • Homa Index calculated according to Matthews' formula
  • Prior endocrine therapy is allowed, in the adjuvant and/or metastatic setting
  • 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.
  • Age 18-75 years
  • Life expectancy of greater than 3 months
  • ECOG performance status \<2
  • Patients must have normal organ and marrow function:
  • leukocytes \>=3,000/μL
  • absolute neutrophil count \>=1,500/μL
  • platelets \>=100,000/μL
  • +6 more criteria

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (25)

P.O. M. Bufalini

Cesena, FC, Italy

Location

UO Oncologia Medica IRCCS IRST

Meldola (FC), FC, 47014, Italy

Location

Ospedale Civile degli Infermi

Faenza, RA, Italy

Location

Ospedale Umberto I

Lugo, RA, Italy

Location

Ospedale Civile Santa Maria delle Croci

Ravenna, RA, Italy

Location

ULSS n.8 Asolo Ospedale di Castelfranco

Asolo, Italy

Location

Centro di Riferimento Oncologico CRO

Aviano, Italy

Location

Ospedale S.Martino

Belluno, Italy

Location

Azienda Ospedaliera "Antonio Cardarelli"

Campobasso, Italy

Location

P.O. "SS. Annunziata"

Chieti, Italy

Location

Presidio Ospedaliero E. Profili

Fabriano, Italy

Location

E.O. Galliera

Genova, Italy

Location

Ospedale di Guastalla

Guastalla, Italy

Location

Azienda per i Servizi Sanitari n.5 "Bassa Friulana"

Latisana, Italy

Location

Presidio Ospedaliero "Vito Fazzi"

Lecce, Italy

Location

ULSS n.13 di Mirano

Mirano, Italy

Location

Arcispedale S. Maria Nuova

Modena, Italy

Location

Azienda Ospedaliera S. Salvatore di Pesaro

Pesaro, Italy

Location

Ospedale S. Spirito

Pescara, Italy

Location

Ospedale Civile di Piacenza

Piacenza, Italy

Location

Azienda Ospedaliera Santa Maria degli Angeli

Pordenone, Italy

Location

Arcispedale S. Maria Nuova

Reggio Emilia, Italy

Location

Ospedale Civile degli Infermi

Rimini, Italy

Location

IRCCS Centro di riferimento Oncologico di Basilicata di Rionero in Vulture

Rionero in Vulture, Italy

Location

Ospedale Nuovo Regina Margherita

Roma, Italy

Location

Related Publications (1)

  • Gennari A, Foca F, Zamarchi R, Rocca A, Amadori D, De Censi A, Bologna A, Cavanna L, Gianni L, Scaltriti L, Rossi E, Facchinetti A, Martini V, Bruzzi P, Nanni O. Insulin-like growth factor-1 receptor (IGF-1R) expression on circulating tumor cells (CTCs) and metastatic breast cancer outcome: results from the TransMYME trial. Breast Cancer Res Treat. 2020 May;181(1):61-68. doi: 10.1007/s10549-020-05596-4. Epub 2020 Mar 21.

MeSH Terms

Conditions

Breast Neoplasms

Interventions

MetforminDoxorubicinCyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

BiguanidesGuanidinesAmidinesOrganic ChemicalsDaunorubicinAnthracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsPolycyclic CompoundsAminoglycosidesGlycosidesCarbohydratesPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedPhosphoramidesOrganophosphorus Compounds

Study Officials

  • Dino Amadori, MD

    IRST IRCCS, Meldola

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 19, 2013

First Posted

June 24, 2013

Study Start

September 1, 2010

Primary Completion

May 1, 2015

Study Completion

May 1, 2015

Last Updated

January 1, 2016

Record last verified: 2015-12

Locations