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

NCT02488564 | Completed Phase 2

• 1 other identifier: IRST174.09
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 9

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.

Conditions

HER-2 Positive Breast Cancer

Keywords

HER-2 Positive Breast Cancer; operable breast cancer; locally advanced breast cancer; no prior therapy; pCR

Outcome Measures

Primary Outcomes (1)

• 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

  up to 36 months

Secondary Outcomes (3)

• clinical response rate (RR)

  up to 36 months

• evaluation of toxicity

  up to 36 months

• conservative surgery rate

  up to 36 months

Study Arms (1)

Liposomal doxorubicin +Docetaxel+Trastuzumab+Metformin

EXPERIMENTAL

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; Drug: Docetaxel; Drug: Trastuzumab; Drug: Metformin

Interventions

Liposomal doxorubicin DRUG

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

Also known as: Myocet®

Liposomal doxorubicin +Docetaxel+Trastuzumab+Metformin

Docetaxel DRUG

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.

Also known as: taxotere

Liposomal doxorubicin +Docetaxel+Trastuzumab+Metformin

Trastuzumab DRUG

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.

Also known as: herceptin

Liposomal doxorubicin +Docetaxel+Trastuzumab+Metformin

Metformin DRUG

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.

Liposomal doxorubicin +Docetaxel+Trastuzumab+Metformin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS: lead

Study Sites (9)

IRST Oncologia medica

Meldola, FC, 47014, Italy

Location

Oncologia Medica AOU Ferrara

Ferrara, FE, 44124, Italy

Location

Oncologia Medica, Policlinico di Modena

Modena, MO, 41100, Italy

Location

Oncologia Medica Ospedale Guglielmo da Saliceto

Piacenza, PC, 29121, Italy

Location

Oncologia , IRCCS azienda ospedaliera S.Maria Nuova

Reggio Emilia, RE, 42123, Italy

Location

U.O Oncologia AUSLdella Romagna

Rimini, RN, 47923, Italy

Location

Day Hospital Oncologico, Ospedale Guastalla

Guastalla, 42016, Italy

Location

Oncologia Medica AUSL Imola

Imola, 40133, Italy

Location

Oncologia Medica AOU Parma

Parma, 43100, Italy

Location

MeSH Terms

Interventions

liposomal doxorubicin; Doxorubicin; Docetaxel; Trastuzumab; Metformin

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biguanides; Guanidines; Amidines

Study Officials

• Anna Fedeli, MD

  IRST IRCCS, Meldola-Cesena

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2015
• First Posted: July 2, 2015
• Study Start: December 17, 2014
• Primary Completion: October 1, 2018
• Study Completion: March 17, 2020
• Last Updated: February 3, 2025

Record last verified: 2025-01

Locations

IT (9)