Description:
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.
Title
- Brief Title: A Study of Liposomal Doxorubicin + Docetaxel + Trastuzumab + Metformin in Operable and Locally Advanced HER2 Positive Breast Cancer
- 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
Clinical Trial IDs
- ORG STUDY ID:
IRST174.09
- NCT ID:
NCT02488564
Conditions
- HER-2 Positive Breast Cancer
Interventions
Drug | Synonyms | Arms |
---|
Liposomal doxorubicin | Myocet® | Liposomal doxorubicin +Docetaxel+Trastuzumab+Metformin |
Docetaxel | taxotere | Liposomal doxorubicin +Docetaxel+Trastuzumab+Metformin |
Trastuzumab | herceptin | Liposomal doxorubicin +Docetaxel+Trastuzumab+Metformin |
Metformin | | Liposomal doxorubicin +Docetaxel+Trastuzumab+Metformin |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
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. | - Liposomal doxorubicin
- Docetaxel
- Trastuzumab
- Metformin
|
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
Maximum Eligible Age: | 75 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Pathologic complete response rate(pCR) |
Time Frame: | up to 36 months |
Safety Issue: | |
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 |
Secondary Outcome Measures
Measure: | clinical response rate (RR) |
Time Frame: | up to 36 months |
Safety Issue: | |
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). |
Measure: | evaluation of toxicity |
Time Frame: | up to 36 months |
Safety Issue: | |
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) |
Measure: | conservative surgery rate |
Time Frame: | up to 36 months |
Safety Issue: | |
Description: | evaluation of the number of patients who underwent conservative surgery |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori |
Trial Keywords
- HER-2 Positive Breast Cancer
- operable breast cancer
- locally advanced breast cancer
- no prior therapy
- pCR
Last Updated
April 21, 2020