Vinorelbine Metronomic Plus Lapatinib for Overexpressing HER-2 Metastatic Breast Cancer

Vinorelbine Metronomic Plus Lapatinib as Salvage Therapy for Patients With Overexpressing HER-2 Metastatic Breast Cancer. A Multicenter Phase II Study

The purpose of this study is to evaluate the safety and efficacy of metronomic oral vinorelbine taken three times a week plus daily lapatinib without break, as salvage treatment in patients with metastatic breast cancer.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Vinorelbine; Drug: Lapatinib

Detailed Description

Continuous administration of oral vinorelbine, given three times a week (metronomic) is feasible and exceptionally well tolerated at doses up to 50 mg. Early results show activity against refractory tumors and provide evidence towards clinical proof of efficacy for metronomic chemotherapy. Recently, lapatinib plus capecitabine was proven superior to capecitabine alone in women with HER2-positive advanced breast cancer that has progressed after treatment with regimens that included an anthracycline, a taxane, and trastuzumab.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece
    • "IASO" General Hospital of Athens, 1st Dep of Medical Oncology
  • Crete
    • Heraklion, Crete, Greece
      • University Hospital of Crete, Dep of Medical Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically- or cytologically- confirmed metastatic breast adenocarcinoma
• Age 18-75 years
• HER2 status positive according to the local institution reported grade 3+ staining intensity (on a scale of 0 to 3) by means of immunohistochemical analysis or grade 2+ staining intensity by means of immunohistochemical analysis with gene amplification on fluorescence in situ hybridization
• Previous therapies had to include, regimens containing an anthracycline and a taxane
• Previous treatment with trastuzumab, alone or in combination with chemotherapy for locally advanced or metastatic disease, is required
• Measurable disease as defined by the presence of at least one measurable lesion (except bone metastases, ascites or pleural effusions)
• Performance status (WHO) 0-2
• Adequate liver (serum bilirubin <1.5 times the upper normal limit; AST and ALT <2.5 times the upper normal limit in the absence of demonstrable liver metastases, or <5 times the upper normal limit in the presence of liver metastases); adequate renal function (serum creatinine <1.5 times the upper normal limit); and bone marrow (neutrophils ≥ 1.5x 109 /L, and platelets ≥ 100x 109 /L) function
• No radiation of measurable disease (except brain metastases)
• No progressive brain metastases according to clinical or radiological criteria
• No brain metastases without prior radiation therapy
• Written informed consent

Exclusion Criteria:

• Patient unable to take oral medication
• Active infection
• History of significant cardiac disease (unstable angina, congestive heart failure, myocardial infarction within the previous 6 months, ventricular arrhythmias)
• Other invasive malignancy except nonmelanoma skin cancer
• Psychiatric illness or social situation that would preclude study compliance
• Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Vinorelbine metronomic/Lapatinib	Drug: Vinorelbine; Vinorelbine p.o (50 mg 3 times a week) until disease progression or appearance of unacceptable toxicity; Other Names: Navelbine; Drug: Lapatinib; Lapatinib p.o every day without interruption disease progression or appearance of unacceptable toxicity; Other Names: Tykerb; Tyverb

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall response rate	3 - 6 month

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival	1 year
Progression Free Survival	1 year
Toxicity profile	21 days
Quality of life assessment	42 days

Collaborators and Investigators

• Sponsor: University Hospital of Crete
• Investigators: Principal Investigator: Dimitris Mavrudis, MD, University Hospital of Crete, Dep of Medical Oncology

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: September 17, 2008
• First Submitted That Met QC Criteria: September 17, 2008
• First Posted (Estimate): September 18, 2008

Study Record Updates

• Last Update Posted (Estimate): September 28, 2015
• Last Update Submitted That Met QC Criteria: September 25, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Targeted therapy; Chemotherapy; Vinorelbine metronomic-lapatinib
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Vinorelbine; Lapatinib
• Other Study ID Numbers: CT/08.27