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

NCT ID: NCT00513058

Last Updated: 2014-01-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-06-30
• Study Completion Date: 2012-04-30

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

Lapatinib

Intervention Type: DRUG

Dose level (DL) 1 : 750 mg/d DL2, DL3, DL4: 1000 mg/d DL5, DL7, DL8: 1250 mg/d DL6: 1500 mg/d

vinorelbine

Intervention Type: DRUG

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

Interventions

Lapatinib

Dose level (DL) 1 : 750 mg/d DL2, DL3, DL4: 1000 mg/d DL5, DL7, DL8: 1250 mg/d DL6: 1500 mg/d

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

TYVERB; NAVELBINE

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

UNICANCER

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pierre Fumoleau, MD, PhD

Role: STUDY_CHAIR

Centre Georges Francois Leclerc

Locations

Centre de Lutte Contre le Cancer Georges-Francois Leclerc

Dijon, , France

Centre Oscar Lambret

Lille, , France

Institut Curie Hopital

Paris, , France

Centre Rene Huguenin

Saint-Cloud, , France

Institut Claudius Regaud

Toulouse, , France

Countries

France

Other Identifiers

FRE-FNCLCC-GEP-01/0506

Identifier Type: OTHER

Identifier Source: secondary_id

2005-005167-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CDR0000558406

Identifier Type: -

Identifier Source: org_study_id