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

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ClinicalTrials.gov Identifier: NCT00513058
Recruitment Status : Completed
First Posted : August 8, 2007
Last Update Posted : January 14, 2014
Sponsor:
Information provided by (Responsible Party):
UNICANCER

Tracking Information
First Submitted Date  ICMJE August 6, 2007
First Posted Date  ICMJE August 8, 2007
Last Update Posted Date January 14, 2014
Study Start Date  ICMJE June 2007
Actual Primary Completion Date May 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 13, 2014)
Toxicity as assessed by NCI CTCAE v3.0 [ Time Frame: during the first cycle of treatment ]
Original Primary Outcome Measures  ICMJE
 (submitted: August 6, 2007)
Toxicity as assessed by NCI CTCAE v3.0
Change History Complete list of historical versions of study NCT00513058 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 13, 2014)
  • Pharmacokinetic interactions between vinorelbine ditartrate (oral or IV) and lapatinib ditosylate [ Time Frame: during the first cycle of treatment ]
  • Tumor response as assessed by RECIST criteria after every 2 courses [ Time Frame: during 6 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 6, 2007)
  • Pharmacokinetic interactions between vinorelbine ditartrate (oral or IV) and lapatinib ditosylate
  • Tumor response as assessed by RECIST criteria after every 2 courses
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Lapatinib and Vinorelbine in Treating Women With HER2-Overexpressing Locally Advanced or Metastatic Breast Cancer
Official Title  ICMJE Phase I Study Evaluating the Combination of Lapatinib + Vinorelbine in Patients With Locally Advanced or Metastatic Breast Cancer Overexpressing HER2
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.

Detailed Description

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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.

Study Type  ICMJE Interventional
Study Phase Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • 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
    Other Name: NAVELBINE
Study Arms 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)
Interventions:
  • Drug: Lapatinib
  • Drug: vinorelbine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 13, 2014)
33
Original Enrollment  ICMJE
 (submitted: August 6, 2007)
60
Actual Study Completion Date April 2012
Actual Primary Completion Date May 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

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
Sex/Gender
Sexes Eligible for Study: Female
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00513058
Other Study ID Numbers  ICMJE CDR0000558406
FRE-FNCLCC-GEP-01/0506 ( Other Identifier: UNICANCER )
2005-005167-28 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party UNICANCER
Study Sponsor  ICMJE UNICANCER
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Pierre Fumoleau, MD, PhD Centre Georges Francois Leclerc
PRS Account UNICANCER
Verification Date January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP