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Liposomal Doxorubicin, Trastuzumab, and Docetaxel in HER2 Positive Metastatic Breast Cancer

Phase 2
Terminated
Conditions
Breast Cancer
Neoplasm Metastasis
Interventions
Drug: Non pegylated liposomal doxorubicin, trastuzumab, docetaxel
Registration Number
NCT00377780
Lead Sponsor
Laurence J.C. van Warmerdam
Brief Summary

This is an open phase II study evaluating the efficacy and safety of the non pegylated liposomal doxorubicin (Myocet®), trastuzumab (Herceptin®), and docetaxel (Taxotere®) combination as first-line treatment of patients with metastatic HER2/neu positive breast cancer.

Detailed Description

Phase II non comparative study, assessing the safety (primarily cardiac safety) and efficacy in patients with locally advanced or metastatic HER2/neu positive breast cancer not yet treated with chemotherapy for metastatic disease.

Myocet and Taxotere will be given for a maximum of 6 cycles, Herceptin treatment for 1 year is recommended.

Endpoints: cardiotoxicity (left ventricular ejection fraction decrease and/or symptoms of heart failure), serious other toxicity, disease progression.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
60
Inclusion Criteria
  • Women with histologically documented metastatic or locally advanced metastatic HER2/neu positive breast cancer at 1st line of palliative chemotherapy.
  • In the case of previous adjuvant or neoadjuvant chemotherapy with anthracyclines or taxanes, this must have been completed more than 12 months before inclusion.
  • In the case of previous adjuvant or neoadjuvant chemotherapy, cumulative anthracycline dose ≤ 240 mg/m2 of doxorubicin or 450 mg/m2 of epirubicin or 75 mg/m2 of mitoxantrone on inclusion.
  • Previous endocrine therapy is authorized (endocrine therapy other than goserelin must be stopped before starting treatment).
  • Previous radiotherapy is authorized, if discontinued ≥ 4 weeks prior to inclusion in the study and if < 10% of the bone marrow was within the irradiated area.
  • Age ≥ 18 years.
  • Performance status 0,1, or 2.
  • Life expectancy ≥ 3 months.
  • Evaluable disease.
  • Normal LVEF (multigated acquisition [MUGA] scan or echocardiography).
  • Normal haematological, hepatic and renal parameters: neutrophils ≥ 1.5 x 10^9/l; platelets ≥ 100 x 10^9/l; hemoglobin (Hb) ≥ 6 mmol/L; total bilirubin ≤ 1.5 times the upper limit of normal (ULN); transaminases ≤ 2.5 x ULN; alkaline phosphatase ≤ 2.5 x ULN; creatinine ≤ 1.5 x ULN.
  • Dated and signed written informed consent.
Exclusion Criteria
  • Previous chemotherapy for metastatic disease.
  • History of other cancer, except for cervical carcinoma in situ treated by cone resection or basal cell or squamous cell skin cancer.
  • History of congestive heart failure or myocardial infarction ≤ 1 year; cardiac function: NYHA ≥ 2 or LVEF < 50%.
  • Uncontrolled significant heart disease, such as unstable angina.
  • Poorly controlled hypertension.
  • Performance status 3, 4.
  • Symptomatic or progressive brain metastases.
  • Active infection or other serious underlying disease.
  • Concomitant participation in other clinical trials.
  • Pregnant women or nursing mothers; patients of childbearing potential without effective contraception.
  • Absolute medical contraindication to the use of corticosteroid premedication.
  • Allergy to polysorbate 80, doxorubicin, or egg lecithin.
  • NCI-CTC grade > 1 peripheral neuropathy.
  • Patients not able to comply with regular medical follow-up

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
1Non pegylated liposomal doxorubicin, trastuzumab, docetaxelMyocet + docetaxel + trastuzumab
Primary Outcome Measures
NameTimeMethod
Signs or symptoms of congestive heart failure (CHF), New York Heart Association (NYHA) class III-IVtreatment period
Cardiotoxicity (definite or probable cardiac death)treatment period
Decline in left ventricular ejection fraction (LVEF) of ≥ 5% to < 50% with mild signs or symptoms of CHF (NYHA class < III)treatment period
Decline in LVEF of ≥ 10% to < 50% without signs or symptoms of CHFtreatment period
Secondary Outcome Measures
NameTimeMethod
Response ratetreatment period
Median time to progressiontreatment period
Progression free survivaltreatment period
Frequency and severity of intercurrent events according to the National Cancer Institute - Common Terminology Criteria (NCI-CTC) classificationtreatment period

Trial Locations

Locations (7)

Ikazia Ziekenhuis

🇳🇱

Rotterdam, Netherlands

VieCuri MC

🇳🇱

Venlo, Netherlands

Streekziekenhuis Koningin Beatrix

🇳🇱

Winterswijk, Netherlands

Catharina-Ziekenhuis

🇳🇱

Eindhoven, Netherlands

Ziekenhuis Rijnstate

🇳🇱

Arnhem, Netherlands

Wilhelmina Ziekenhuis

🇳🇱

Assen, Netherlands

Maxima Medisch Centrum

🇳🇱

Veldhoven, Netherlands

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