Primary Chemotherapy in Patients With HER2-positive Early Breast Cancer (LAPADO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01172223
Recruitment Status : Completed
First Posted : July 29, 2010
Last Update Posted : November 2, 2016
Information provided by (Responsible Party):
Prof Dirk Elling, Sana-Klinikum Lichtenberg

Brief Summary:

Open-label, multicenter phase I/II trial. Patients with HER2-positive (overexpressing or amplified), invasive breast cancer with T1c N1-2 or T2 N0-2 disease will be treated with

  • Non-pegylated liposomal doxorubicin (NPLD; Myocet, 60 mg/m^2 i.v. day 1 q3 weeks),
  • Paclitaxel (175 mg/m^2 i.v. day 1 q3 weeks), and
  • Lapatinib (GW572016, Tykerb, 750-1500 mg/d orally daily until the day of the definitive surgery) Treatment is planned for 6 cycles unless there is evidence of unacceptable toxicity, disease progression or inadequate efficacy (defined as a decrease in tumor size <25% after 4 courses measured by ultrasound or MR-mammography), or if the patient requested to be released.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Myocet (Non-pegylated liposomal doxorubicin (NPLD)) Drug: Paclitaxel Drug: Lapatinib (GW572016, Tykerb) Phase 1 Phase 2

Detailed Description:
Breast cancer is the most common malignancy affecting females in northern Europe and North America, corresponding to an age-corrected annual incidence of 100 to 120 per 100000 females. Approximately 30-40% of all patients treated with curative intent will develop metastatic disease. Perioperative systemic treatment has made a major impact on relapse-free and overall survival of women with early-stage breast cancer [ , ] with therapeutic strategies being based on the endocrine responsiveness and the estimated risk of relapse defined by tumor size, axillary lymph node involvement, histologic and nuclear grade, lymphatic and/or vascular invasion, HER2/neu-overexpression and age [ ]. Perioperative therapy has traditionally been administered postoperatively, but chemotherapy is increasingly utilized in the preoperative setting as it can significantly improve the rate of breast conserving surgery, and new regimens can be evaluated rapidly and more precisely.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 81 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Trial of Primary Chemotherapy With Non-pegylated Liposomal Doxorubicin, Paclitaxel and Lapatinib in Patients With HER2-positive Early
Study Start Date : September 2007
Actual Primary Completion Date : January 2013
Actual Study Completion Date : December 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: LAPADO
Non-pegylated liposomal doxorubicin (NPLD; Myocet, 60 mg/m2 i.v. day 1 q3 weeks), Paclitaxel (175 mg/m2 i.v. day 1 q3 weeks), and Lapatinib (GW572016, Tykerb, 750-1500 mg/d orally daily until the day of the definitive surgery)
Drug: Myocet (Non-pegylated liposomal doxorubicin (NPLD))
60 mg/m^2 i.v. day 1 q3 weeks

Drug: Paclitaxel
175 mg/m^2 i.v. day 1 q3 weeks

Drug: Lapatinib (GW572016, Tykerb)
750-1500 mg/d orally daily until the day of the definitive surgery

Primary Outcome Measures :
  1. Determine the optimal doses for NPLD, paclitaxel and lapatinib (phase I) [ Time Frame: every 3 weeks ]
  2. Evaluate the pathological response to NPLD, paclitaxel and lapatinib (phase II) [ Time Frame: every 6 weeks ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed breast cancer
  • T1c N1-2 or T2 N0-2 disease
  • HER2-positive tumours with 3+ intensity on immunohistochemical staining for HER2 or amplification of the HER2 gene on fluorescence in situ hybridization (FISH)
  • No prior systemic treatment regimens for breast cancer
  • Adequate hematologic function (ANC 1500 cells/µl, platelet count 100000/µl, and hemoglobin 8g/dl).
  • Serum creatinine concentration < 1.5 times the upper limit of normal (ULN) and/or creatinine clearance >60 ml/min
  • Bilirubin level < 1.5 X ULN
  • Normal cardiac function with a left ventricular ejection fraction of at least 50% (as assessed by quantitative echocardiogram or MUGA scan)
  • Karnofsky performance status 80%
  • Age 18 years
  • If the patient is of childbearing potential, she agrees to: comply with effective contraceptive measures, has been using adequate contraception since the last menses, will use adequate contraception during the study, and has a negative pregnancy test within one week of study entry
  • Written informed consent prior to admission to this study

Exclusion Criteria:

  • Male patients
  • Inflammatory or bilateral breast cancer
  • Evidence of distant metastases
  • Previous systemic or local treatment for breast cancer (including surgery, radiotherapy, cytotoxic and endocrine treatments)
  • Past or current history of other neoplasms, except for
  • Curatively treated non-melanoma skin cancer
  • Adequately treated in situ carcinoma of the cervix
  • Other cancer curatively treated and with no evidence of disease for at least 5 years
  • Significant cardiac disease, including angina pectoris, severe cardiac arrhythmia requiring medication, severe conduction abnormalities, clinically significant valvular disease, cardiomegaly, ventricular hypertrophy, poorly uncontrolled hypertension (resting diastolic blood pressure >115 mmHg), prior myocardial infarction, CHF, or other cardiomyopathy
  • Preexisting sensoric or motor polyneuropathy Grade 2 according to NCI CTC
  • Serious intercurrent medical or psychiatric illness, including serious active infection
  • Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational drug within 30 days prior to study entry.
  • Detained persons or prisoners
  • Pregnant or nursing women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01172223

Sana Klinikum Lichtenberg
Berlin, Germany
Sponsors and Collaborators
Prof Dirk Elling
Principal Investigator: Dirk Elling Sana Klinikum Lichtenberg, Berlin

Responsible Party: Prof Dirk Elling, Professor, Sana-Klinikum Lichtenberg Identifier: NCT01172223     History of Changes
Other Study ID Numbers: LAPADO-Study
2007-000924-42 ( EudraCT Number )
First Posted: July 29, 2010    Key Record Dates
Last Update Posted: November 2, 2016
Last Verified: October 2016

Keywords provided by Prof Dirk Elling, Sana-Klinikum Lichtenberg:
early breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Liposomal doxorubicin
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Protein Kinase Inhibitors