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Lapatinib and Vinorelbine in Treating Women With HER2-Overexpressing Locally Advanced or Metastatic Breast Cancer

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: NCT00513058
Recruitment Status : Completed
First Posted : August 8, 2007
Last Update Posted : January 14, 2014
Information provided by (Responsible Party):

Brief Summary:

RATIONALE: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as vinorelbine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving lapatinib together with vinorelbine may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of lapatinib and vinorelbine in treating women with HER2-overexpressing locally advanced or metastatic breast cancer.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Lapatinib Drug: vinorelbine Phase 1

Detailed Description:



  • Evaluate the tolerability and feasibility of the lapatinib ditosylate and vinorelbine ditartrate combination by determining the maximum tolerated dose of vinorelbine ditartrate in combination with a biologically active dose of lapatinib ditosylate.


  • Determine the maximum administered dose.
  • Investigate the pharmacokinetic interactions related to the combination of vinorelbine ditartrate and lapatinib ditosylate.
  • Determine the toxicity of vinorelbine ditartrate and lapatinib ditosylate.
  • Determine the objective response rate in patients with measurable lesions.
  • Validate the safety and efficacy of the oral vinorelbine ditartrate and lapatinib ditosylate combination, according to the vinorelbine ditartrate oral/IV dose equivalence.

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive oral lapatinib ditosylate on days -7 to 21 for course 1 and on days 1-21 for all other courses. Patients also receive vinorelbine ditartrate IV over 15 minutes on days 1 and 8. Courses repeat every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-9 patients receive escalating doses of lapatinib ditosylate and vinorelbine ditartrate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 9 patients experience dose-limiting toxicity during course 1.

Once the MTD is determined for oral lapatinib ditosylate and IV vinorelbine ditartrate, an additional cohort of 9 patients receive oral vinorelbine ditartrate with oral lapatinib ditosylate as above.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 33 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study Evaluating the Combination of Lapatinib + Vinorelbine in Patients With Locally Advanced or Metastatic Breast Cancer Overexpressing HER2
Study Start Date : June 2007
Actual Primary Completion Date : May 2010
Actual Study Completion Date : April 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: lapatinib + vinorelbine
  • starting with loading dose of lapatinib per os for 7 days
  • then, combining lapatinib (oral daily continuous) + vinorelbine (intravenous, day 1 and 8 every 3 weeks)
Drug: Lapatinib
Dose level (DL) 1 : 750 mg/d DL2, DL3, DL4: 1000 mg/d DL5, DL7, DL8: 1250 mg/d DL6: 1500 mg/d
Other Name: TYVERB

Drug: vinorelbine
DL1, DL2: 20 mg/m2 DL3: 22.5 mg/m2 DL4, DL5, DL6: 25 mg/m2 DL7: 27.5 mg/m2 DL8: 30 mg/m2

Primary Outcome Measures :
  1. Toxicity as assessed by NCI CTCAE v3.0 [ Time Frame: during the first cycle of treatment ]

Secondary Outcome Measures :
  1. Pharmacokinetic interactions between vinorelbine ditartrate (oral or IV) and lapatinib ditosylate [ Time Frame: during the first cycle of treatment ]
  2. Tumor response as assessed by RECIST criteria after every 2 courses [ Time Frame: during 6 months ]

Information from the National Library of Medicine

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


  • Histologically confirmed advanced breast cancer (metastatic or locally advanced)
  • Tumor overexpressing HER2 (HER2 3+ by IHC OR HER2 2+ by IHC and FISH positive) in samples from the primary and/or secondary tumor
  • Measurable or evaluable disease
  • Cancer is progressive after treatment with at least 1 line or, at most, 2 lines, of chemotherapy that included trastuzumab (Herceptin®)
  • Patients presenting with treated asymptomatic cerebral metastases or leptomeningeal metastases may be included if they are neurologically stable and have not received steroids or anticonvulsant treatment for at least 4 weeks before study entry


Inclusion criteria:

  • Female
  • Menopausal status not specified
  • Patients must have an estimated survival of at least 3 months
  • WHO performance status (ECOG) 0-2
  • Hemoglobin ≥ 9 g/dL
  • ANC ≥ 1,500/mm³
  • Platelets ≥ 100,000/mm³
  • Total bilirubin ≤ 2.5 mg/dL
  • ALT and AST ≤ 3 times upper limit of normal
  • Serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 40 mL/min
  • LVEF ≥ 50% (echographic or isotopic method)
  • Potentially reproductive patients must agree to use an effective contraceptive method while on study treatment
  • Patients must be affiliated with a Social Security system

Exclusion criteria:

  • Uncontrolled cardiac pathology
  • Dysphagia or inability to swallow the vinorelbine ditartrate soft capsules
  • Malabsorption syndrome or disease significantly affecting gastrointestinal function
  • Preexisting neuropathy (grade ≥ 2)
  • Pregnant women, women who are likely to become pregnant, or women who are breastfeeding
  • Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
  • Individuals deprived of liberty

Exclusion criteria:

  • Prior major resection of stomach or proximal bowel that could affect absorption of oral drugs
  • Prior vinorelbine

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): NCT00513058

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Centre de Lutte Contre le Cancer Georges-Francois Leclerc
Dijon, France, 21079
Centre Oscar Lambret
Lille, France, 59020
Institut Curie Hopital
Paris, France, 75248
Centre Rene Huguenin
Saint Cloud, France, 92211
Institut Claudius Regaud
Toulouse, France, 31052
Sponsors and Collaborators
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Study Chair: Pierre Fumoleau, MD, PhD Centre Georges Francois Leclerc

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Responsible Party: UNICANCER Identifier: NCT00513058     History of Changes
Other Study ID Numbers: CDR0000558406
FRE-FNCLCC-GEP-01/0506 ( Other Identifier: UNICANCER )
2005-005167-28 ( EudraCT Number )
First Posted: August 8, 2007    Key Record Dates
Last Update Posted: January 14, 2014
Last Verified: January 2014

Keywords provided by UNICANCER:
metastatic breast cancer
advanced breast cancer

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators