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

NCT02488564

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT02488564

Trial Eligibility

Document

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

DrugSynonymsArms
Liposomal doxorubicinMyocet®Liposomal doxorubicin +Docetaxel+Trastuzumab+Metformin
DocetaxeltaxotereLiposomal doxorubicin +Docetaxel+Trastuzumab+Metformin
TrastuzumabherceptinLiposomal doxorubicin +Docetaxel+Trastuzumab+Metformin
MetforminLiposomal 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

NameTypeDescriptionInterventions
Liposomal doxorubicin +Docetaxel+Trastuzumab+MetforminExperimentalDay 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