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A Study of Liposomal Doxorubicin + Docetaxel + Trastuzumab + Metformin in Operable and Locally Advanced HER2 Positive Breast Cancer (met-HEReMYTA)

Primary Purpose

HER-2 Positive Breast Cancer

Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Liposomal doxorubicin
Docetaxel
Trastuzumab
Metformin
Sponsored by
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HER-2 Positive Breast Cancer focused on measuring HER-2 Positive Breast Cancer, operable breast cancer, locally advanced breast cancer, no prior therapy, pCR

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must have histologically confirmed breast cancer
  • HER2 overexpressing cancer
  • Patients with operable breast cancer (T1c and cytologically N1-2, or cT2-3, N0-N2, M0) or locally advanced breast cancer (T4a-d, N0-N2, M0) (AJCC 7th edition 2010).
  • No prior therapy for breast cancer
  • Both sexes, age ≥ 18 years and < 75 years
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Life expectancy > 3 months
  • Neutrophil count ≥ 2 x 109/ L, leukocytes count ≥ 3 x 109/ L and platelet count ≥ 100 x 109/ L
  • Total bilirubin ≤ 1 upper-normal limits (UNL) of the Institutional normal values and alanine aminotransferase (ASAT (GOT) and/or alanine aminotransferase ALAT (GPT) ≤ 2.5 UNL, alkaline phosphatase ≤ 5 UNL. Patients with ASAT and/or ALAT > 1.5 UNL and alkaline phosphatase > 2.5 UNL aren't eligible for the trial.
  • Creatinine ≤ 1.5 mg/dL
  • Left ventricular ejection fraction (LVEF) ≥ 50% (evaluated by echocardiogram or multiple gated acquisition scan (MUGA) scan -only one method must be employed for each patient)
  • Written informed consent
  • Homa Index calculated using the Matthews'formula

EXCLUSION CRITERIA:

  • Prior chemotherapy or radiotherapy for breast cancer.
  • History of prior malignancy in the last 10 years (other than non-melanoma skin cancer or excised cervical carcinoma in situ).
  • Other serious illness or medical condition
  • Congestive heart failure or angina pectoris even if medically controlled. Previous history of myocardial infarction, uncontrolled high risk hypertension or arrhythmia
  • History of significant neurologic or psychiatric disorders including dementia or seizures
  • Active infection
  • Concurrent treatment with other experimental drugs.
  • Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
  • Geographic inaccessibility to treatment and followup
  • Pregnant and lactating women
  • Diabetes-insulin dependant and non-insulin dependant

Sites / Locations

  • IRST Oncologia medica
  • Oncologia Medica AOU Ferrara
  • Oncologia Medica, Policlinico di Modena
  • Oncologia Medica Ospedale Guglielmo da Saliceto
  • Oncologia , IRCCS azienda ospedaliera S.Maria Nuova
  • U.O Oncologia AUSLdella Romagna
  • Day Hospital Oncologico, Ospedale Guastalla
  • Oncologia Medica AUSL Imola
  • Oncologia Medica AOU Parma

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Liposomal doxorubicin +Docetaxel+Trastuzumab+Metformin

Arm Description

Day 1: Liposome-encapsulated doxorubicin, 50 mg/m2 IV 1 hour infusion; Day 2 and 9: Docetaxel, 30 mg/m2 IV 1 hour infusion; Day 2, 9 and 16: Trastuzumab 4 mg/kg for the first infusion loading dose, then 2 mg/kg/week for subsequent injections. Day -13 to 0: Metformin is administered as single agent. From day -13 to day -11, Metformin 1000 mg will be administered once a day; from day -10 Metformin 1000 mg will be administered twice a day continuously until end of the study treatment.

Outcomes

Primary Outcome Measures

Pathologic complete response rate(pCR)
Complete pathologic response will be defined as no invasive residuals in breast and axillary nodes. In situ tumor residuals are considered as complete response rate

Secondary Outcome Measures

clinical response rate (RR)
The clinical response rate (RR) will be including Pathological Complete Response, Clinical Complete Response and Clinical Partial Response (Response Evaluation Criteria in Solid Tumors (RECIST) criteria).
evaluation of toxicity
All patients will be evaluable for toxicity from the time of their first treatment with Metformine. The toxicity will be recorded according to the CTC-AE, version 4.0 in the safety population until Follow-up is completed (36 months)
conservative surgery rate
evaluation of the number of patients who underwent conservative surgery

Full Information

First Posted
June 17, 2015
Last Updated
April 20, 2020
Sponsor
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
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1. Study Identification

Unique Protocol Identification Number
NCT02488564
Brief Title
A Study of Liposomal Doxorubicin + Docetaxel + Trastuzumab + Metformin in Operable and Locally Advanced HER2 Positive Breast Cancer
Acronym
met-HEReMYTA
Official Title
Clinical and Translational Phase II Study of Liposomal Doxorubicin Plus Docetaxel and Trastuzumab With Metformin as Primary Systemic Therapy for Operable and Locally Advanced Recombinant Human ErbB-2 (HER2) Positive Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
December 17, 2014 (Actual)
Primary Completion Date
October 2018 (Actual)
Study Completion Date
April 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
It is a multicenter, open-label, two stage phase II trial, to assess activity, safety and potential early predictors of response in neoadjuvant setting. Patients with operable breast cancer (T1c and cytologically N1-2, or cT2-3, N0-N2, M0) or locally advanced breast cancer (T4a-d, N0-N2, M0) with overexpression or amplification of HER2 (AJCC 7th edition 2010) are included in the study. The primary objective is to evaluate the pathological complete response rate (pCR). The secondary objectives are: to evaluate the clinical response rate (RR). to evaluate the feasibility and systemic tolerance, with particular attention to cardiac toxicity. to evaluate the conservative surgery rate. Total duration of the trial is 36 months; planned treatment are 6 cycles of chemotherapy. At every cycle (every 21 days) will be administered: Day 1: Liposome-encapsulated doxorubicin, 50 mg/m2 IV 1 hour infusion; Day 2 and 9: Docetaxel, 30 mg/m2 IV 1 hour infusion; Day 2, 9 and 16: Trastuzumab 4 mg/kg for the first infusion loading dose, then 2 mg/kg/week for subsequent injections. Day -13 to 0: Metformin is administered as single agent. From day -13 to day -11, Metformin 1000 mg will be administered once a day; from day -10 Metformin 1000 mg will be administered twice a day continuously until end of the study treatment.
Detailed Description
Multi-center, open-label phase II trial to assess activity of this chemotherapy scheme evaluated by pathologic complete response rate (pCR). Planned treatment are 6 cycles of chemotherapy. At every cycle (every 21 days) will be administered: Day 1: Liposome-encapsulated doxorubicin, 50 mg/m2 IV 1 hour infusion; Day 2 and 9: Docetaxel, 30 mg/m2 IV 1 hour infusion; Day 2, 9 and 16: Trastuzumab 4 mg/kg for the first infusion loading dose, then 2 mg/kg/week for subsequent injections Day -13 to 0: Metformin is administered as single agent. From day -13 to day -11, Metformin 1000 mg will be administered once a day; from day -10 Metformin 1000 mg will be administered twice a day continuously until end of the study treatment. Total duration of the trial: 36 months Enrollment period: 24 months Treatment: maximum of 6 cycles (5 months) per patient Follow-up for recurrence: every six months for 5 years, than once a year until 10 years after surgery.It's necessary to recruit 46 patients for clinical objectives evaluation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HER-2 Positive Breast Cancer
Keywords
HER-2 Positive Breast Cancer, operable breast cancer, locally advanced breast cancer, no prior therapy, pCR

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Liposomal doxorubicin +Docetaxel+Trastuzumab+Metformin
Arm Type
Experimental
Arm Description
Day 1: Liposome-encapsulated doxorubicin, 50 mg/m2 IV 1 hour infusion; Day 2 and 9: Docetaxel, 30 mg/m2 IV 1 hour infusion; Day 2, 9 and 16: Trastuzumab 4 mg/kg for the first infusion loading dose, then 2 mg/kg/week for subsequent injections. Day -13 to 0: Metformin is administered as single agent. From day -13 to day -11, Metformin 1000 mg will be administered once a day; from day -10 Metformin 1000 mg will be administered twice a day continuously until end of the study treatment.
Intervention Type
Drug
Intervention Name(s)
Liposomal doxorubicin
Other Intervention Name(s)
Myocet®
Intervention Description
50 mg/m2 by intravenous infusion over a period of 1 hour on day 1 of each cycle repeated every 21 days. A final concentration of between 0.4 to 1.2 mg/ml doxorubicin hydrochloride, is required
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Other Intervention Name(s)
taxotere
Intervention Description
30 mg/m2 by intravenous infusion over a period of 1 hour on day 2 and 9, every 3 week.They will be given for 6 cycles.
Intervention Type
Drug
Intervention Name(s)
Trastuzumab
Other Intervention Name(s)
herceptin
Intervention Description
4 mg/kg for the first administration (day 2 cycle 1) and 2 mg/kg for subsequent administrations. Trastuzumab will be given weekly for the duration of chemotherapy (day 2, 9, 16), then will be administered at the dose of 6 mg/Kg every 3 weeks until completion of 52 weeks of treatment.
Intervention Type
Drug
Intervention Name(s)
Metformin
Intervention Description
It is administered as single agent from day -13 to 0. From day -13 to day -11, Metformin 1000 mg will be administered once a day; from day -10, Metformin 1000 mg will be administered twice a day continuously until end of the study treatment.
Primary Outcome Measure Information:
Title
Pathologic complete response rate(pCR)
Description
Complete pathologic response will be defined as no invasive residuals in breast and axillary nodes. In situ tumor residuals are considered as complete response rate
Time Frame
up to 36 months
Secondary Outcome Measure Information:
Title
clinical response rate (RR)
Description
The clinical response rate (RR) will be including Pathological Complete Response, Clinical Complete Response and Clinical Partial Response (Response Evaluation Criteria in Solid Tumors (RECIST) criteria).
Time Frame
up to 36 months
Title
evaluation of toxicity
Description
All patients will be evaluable for toxicity from the time of their first treatment with Metformine. The toxicity will be recorded according to the CTC-AE, version 4.0 in the safety population until Follow-up is completed (36 months)
Time Frame
up to 36 months
Title
conservative surgery rate
Description
evaluation of the number of patients who underwent conservative surgery
Time Frame
up to 36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have histologically confirmed breast cancer HER2 overexpressing cancer Patients with operable breast cancer (T1c and cytologically N1-2, or cT2-3, N0-N2, M0) or locally advanced breast cancer (T4a-d, N0-N2, M0) (AJCC 7th edition 2010). No prior therapy for breast cancer Both sexes, age ≥ 18 years and < 75 years Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Life expectancy > 3 months Neutrophil count ≥ 2 x 109/ L, leukocytes count ≥ 3 x 109/ L and platelet count ≥ 100 x 109/ L Total bilirubin ≤ 1 upper-normal limits (UNL) of the Institutional normal values and alanine aminotransferase (ASAT (GOT) and/or alanine aminotransferase ALAT (GPT) ≤ 2.5 UNL, alkaline phosphatase ≤ 5 UNL. Patients with ASAT and/or ALAT > 1.5 UNL and alkaline phosphatase > 2.5 UNL aren't eligible for the trial. Creatinine ≤ 1.5 mg/dL Left ventricular ejection fraction (LVEF) ≥ 50% (evaluated by echocardiogram or multiple gated acquisition scan (MUGA) scan -only one method must be employed for each patient) Written informed consent Homa Index calculated using the Matthews'formula EXCLUSION CRITERIA: Prior chemotherapy or radiotherapy for breast cancer. History of prior malignancy in the last 10 years (other than non-melanoma skin cancer or excised cervical carcinoma in situ). Other serious illness or medical condition Congestive heart failure or angina pectoris even if medically controlled. Previous history of myocardial infarction, uncontrolled high risk hypertension or arrhythmia History of significant neurologic or psychiatric disorders including dementia or seizures Active infection Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational agents within 30 days prior to study screening. Geographic inaccessibility to treatment and followup Pregnant and lactating women Diabetes-insulin dependant and non-insulin dependant
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anna Fedeli, MD
Organizational Affiliation
IRST IRCCS, Meldola-Cesena
Official's Role
Principal Investigator
Facility Information:
Facility Name
IRST Oncologia medica
City
Meldola
State/Province
FC
ZIP/Postal Code
47014
Country
Italy
Facility Name
Oncologia Medica AOU Ferrara
City
Ferrara
State/Province
FE
ZIP/Postal Code
44124
Country
Italy
Facility Name
Oncologia Medica, Policlinico di Modena
City
Modena
State/Province
MO
ZIP/Postal Code
41100
Country
Italy
Facility Name
Oncologia Medica Ospedale Guglielmo da Saliceto
City
Piacenza
State/Province
PC
ZIP/Postal Code
29121
Country
Italy
Facility Name
Oncologia , IRCCS azienda ospedaliera S.Maria Nuova
City
Reggio Emilia
State/Province
RE
ZIP/Postal Code
42123
Country
Italy
Facility Name
U.O Oncologia AUSLdella Romagna
City
Rimini
State/Province
RN
ZIP/Postal Code
47923
Country
Italy
Facility Name
Day Hospital Oncologico, Ospedale Guastalla
City
Guastalla
ZIP/Postal Code
42016
Country
Italy
Facility Name
Oncologia Medica AUSL Imola
City
Imola
ZIP/Postal Code
40133
Country
Italy
Facility Name
Oncologia Medica AOU Parma
City
Parma
ZIP/Postal Code
43100
Country
Italy

12. IPD Sharing Statement

Learn more about this trial

A Study of Liposomal Doxorubicin + Docetaxel + Trastuzumab + Metformin in Operable and Locally Advanced HER2 Positive Breast Cancer

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