Lapatinib and Vinorelbine in Treating Women With HER2-Overexpressing Locally Advanced or Metastatic Breast Cancer
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.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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|
- Toxicity as assessed by NCI CTCAE v3.0 [ Time Frame: during the first cycle of treatment ] [ Designated as safety issue: Yes ]
- Pharmacokinetic interactions between vinorelbine ditartrate (oral or IV) and lapatinib ditosylate [ Time Frame: during the first cycle of treatment ] [ Designated as safety issue: Yes ]
- Tumor response as assessed by RECIST criteria after every 2 courses [ Time Frame: during 6 months ] [ Designated as safety issue: No ]
|Study Start Date:||June 2007|
|Study Completion Date:||April 2012|
|Primary Completion Date:||May 2010 (Final data collection date for primary outcome measure)|
Experimental: lapatinib + vinorelbine
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: TYVERBDrug: 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
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00513058
|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|
|Study Chair:||Pierre Fumoleau, MD, PhD||Centre Georges Francois Leclerc|