HER-2 Positive Breast CancerPhase 2met-HEReMYTANCT02488564
A Study of Liposomal Doxorubicin+Docetaxel+Trastuzumab+Metformin in Operable and Locally Advanced HER2 Positive Breast Cancer
A Phase 2 study testing Liposomal doxorubicin, Docetaxel and Trastuzumab in people with HER-2 Positive Breast Cancer, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 9 sites in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- HER-2 Positive Breast Cancer
- What is being tested?
- Liposomal doxorubicin, Docetaxel and Trastuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 9 sitesItaly
- Study dates
- 17 Dec 2014to 17 Mar 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Italy9 sites
Oncologia Medica AOU Ferrara
Ferrara, FE, 44124
Day Hospital Oncologico, Ospedale Guastalla
Guastalla, 42016
Oncologia Medica AUSL Imola
Imola, 40133
IRST Oncologia medica
Meldola, FC, 47014
Oncologia Medica, Policlinico di Modena
Modena, MO, 41100
Oncologia Medica AOU Parma
Parma, 43100
Oncologia Medica Ospedale Guglielmo da Saliceto
Piacenza, PC, 29121
Oncologia , IRCCS azienda ospedaliera S.Maria Nuova
Reggio Emilia, RE, 42123
U.O Oncologia AUSLdella Romagna
Rimini, RN, 47923
About this study
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
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).
Read more
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.
Read the 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.
- Conditions
- HER-2 Positive Breast Cancer
- Being tested
- Liposomal doxorubicin, Docetaxel, Trastuzumab, Metformin
- Keywords
- HER-2 Positive Breast Cancer, operable breast cancer, locally advanced breast cancer, no prior therapy, pCR
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liposomal doxorubicinDrug
Also called Myocet®
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
DocetaxelDrug
Also called taxotere
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.
TrastuzumabDrug
Also called herceptin
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.
MetforminDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Liposomal doxorubicin; Drug: Docetaxel; Drug: Trastuzumab; Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: up to 36 months
Secondary outcomes (3)
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).
Measured: up to 36 months
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)
Measured: up to 36 months
conservative surgery rate
evaluation of the number of patients who underwent conservative surgery
Measured: up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2015 (estimated)
- Study start17 Dec 2014
- Primary completionOct 2018
- Study completion17 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER-2 Positive Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anna Fedeli, MD, Principal investigator, IRST IRCCS, Meldola-Cesena
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02488564
- Sponsor's protocol ID
- IRST174.09
- Acronym
- met-HEReMYTA
- Status last verified
- Jan 2025
- First submitted
- 17 Jun 2015
- Last updated
- 3 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02488564
- Acronym / sponsor ID
- met-HEReMYTA / IRST174.09
- Conditions
- HER-2 Positive Breast Cancer
- Keywords
- HER-2 Positive Breast Cancer, operable breast cancer, locally advanced breast cancer, no prior therapy, pCR
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCSUniversity, hospital or other
- Study start
- 17 Dec 2014 (actual)
- Primary completion
- Oct 2018 (actual)
- Study completion
- 17 Mar 2020 (actual)
- First posted
- 2 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Liposomal doxorubicin +Docetaxel+Trastuzumab+Metformin | Experimental | Drug: Liposomal doxorubicin, Drug: Docetaxel, Drug: Trastuzumab, Drug: MetforminDay 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Liposomal doxorubicinAlso: Myocet®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 | Drug | Liposomal doxorubicin +Docetaxel+Trastuzumab+Metformin |
| DocetaxelAlso: taxotere30 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. | Drug | Liposomal doxorubicin +Docetaxel+Trastuzumab+Metformin |
| TrastuzumabAlso: herceptin4 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. | Drug | Liposomal doxorubicin +Docetaxel+Trastuzumab+Metformin |
| MetforminIt 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. | Drug | Liposomal doxorubicin +Docetaxel+Trastuzumab+Metformin |
Primary outcome
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
3 secondary outcomes
clinical response rate (RR)
Time frame: up to 36 months
evaluation of toxicity
Time frame: up to 36 months
conservative surgery rate
Time frame: up to 36 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anna Fedeli, MD principal investigator
IRST IRCCS, Meldola-Cesena
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Liposomal doxorubicin, Docetaxel and Trastuzumab in people with HER-2 Positive Breast Cancer, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 9 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathologic complete response rate(pCR) (time frame: up to 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2025.