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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02488564
Recruitment Status : Active, not recruiting
First Posted : July 2, 2015
Last Update Posted : November 13, 2018
Sponsor:
Information provided by (Responsible Party):
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

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.


Condition or disease Intervention/treatment Phase
HER-2 Positive Breast Cancer Drug: Liposomal doxorubicin Drug: Docetaxel Drug: Trastuzumab Drug: Metformin Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 49 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : October 2014
Actual Primary Completion Date : October 2018
Estimated Study Completion Date : October 2019


Arm Intervention/treatment
Experimental: Liposomal doxorubicin +Docetaxel+Trastuzumab+Metformin

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.

Drug: Liposomal doxorubicin
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
Other Name: Myocet®

Drug: Docetaxel
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.
Other Name: taxotere

Drug: Trastuzumab
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.
Other Name: herceptin

Drug: Metformin
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 Measures :
  1. Pathologic complete response rate(pCR) [ Time Frame: up to 36 months ]
    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 :
  1. clinical response rate (RR) [ Time Frame: up to 36 months ]
    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).

  2. evaluation of toxicity [ Time Frame: up to 36 months ]
    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)

  3. conservative surgery rate [ Time Frame: up to 36 months ]
    evaluation of the number of patients who underwent conservative surgery



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02488564


Locations
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Italy
IRST Oncologia medica
Meldola, FC, Italy, 47014
Oncologia Medica AOU Ferrara
Ferrara, FE, Italy, 44124
Oncologia Medica, Policlinico di Modena
Modena, MO, Italy, 41100
Oncologia Medica Ospedale Guglielmo da Saliceto
Parma, PR, Italy, 29121
Oncologia , IRCCS azienda ospedaliera S.Maria Nuova
Reggio Emilia, RE, Italy, 42123
U.O Oncologia AUSLdella Romagna
Rimini, RN, Italy, 47923
Day Hospital Oncologico, Ospedale Guastalla
Guastalla, Italy, 42016
Oncologia Medica AUSL Imola
Imola, Italy, 40133
Oncologia Medica AOU Parma
Parma, Italy, 43100
Sponsors and Collaborators
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Investigators
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Principal Investigator: Anna Fedeli, MD IRST IRCCS, Meldola-Cesena

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Responsible Party: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
ClinicalTrials.gov Identifier: NCT02488564    
Other Study ID Numbers: IRST174.09
First Posted: July 2, 2015    Key Record Dates
Last Update Posted: November 13, 2018
Last Verified: November 2018
Keywords provided by Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori:
HER-2 Positive Breast Cancer
operable breast cancer
locally advanced breast cancer
no prior therapy
pCR
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Metformin
Docetaxel
Doxorubicin
Liposomal doxorubicin
Trastuzumab
Hypoglycemic Agents
Physiological Effects of Drugs
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents, Immunological