Chemotherapy Plus Trastuzumab in Treating Patients With Breast Cancer

Dartmouth Health

Status and phase

Completed

Phase 1

Conditions

Breast Cancer

Treatments

Biological: trastuzumab

Drug: vinorelbine ditartrate

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00014430

NCI-G01-1932

DMS-9904

CDR0000068543

P30CA023108 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase I trial to study the effectiveness of vinorelbine plus trastuzumab in treating patients who have refractory or metastatic breast cancer.

Full description

OBJECTIVES:

Determine the maximum tolerated dose of vinorelbine in combination with trastuzumab (Herceptin) in patients with HER-2/neu overexpressing unresectable or metastatic non-small cell lung cancer (closed to accrual as of 4/16/01) or refractory locally advanced or metastatic breast cancer.
Determine the pharmacokinetic and pharmacodynamic profiles of this regimen in this patient population.
Determine the objective response rate of patients treated with this regimen.

OUTLINE: This is a dose-escalation study of vinorelbine.

Patients receive vinorelbine IV over 5-10 minutes on days 1 and 8, and trastuzumab (Herceptin) IV over 30-90 minutes on days 8 and 15 of course 1 and days 1, 8, and 15 of all subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3 to 6 patients receive escalating doses of vinorelbine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: Approximately 30-35 patients will be accrued for this study.

Enrollment

13 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically confirmed unresectable or metastatic non-small cell lung cancer
- Stage IIIB or IV (closed to accrual as of 4/16/01) OR
Histologically confirmed locally advanced breast cancer that has progressed after first-line chemotherapy or metastatic breast cancer
HER-2/neu overexpression (1+ to 3+)
Hormone receptor status:
- Not specified

PATIENT CHARACTERISTICS:

Age:

18 and over

Menopausal status:

Not specified

Performance status:

Karnofsky 60-100%

Life expectancy:

Not specified

Hematopoietic:

Absolute neutrophil count at least 2,000/mm3
Platelet count at least 100,000/mm3

Hepatic:

Bilirubin no greater than 2 times upper limit of normal (ULN)
ALT no greater than 3 times ULN

Renal:

Creatinine no greater than 2 times ULN

Cardiovascular:

No prior or concurrent unstable angina
No prior symptomatic congestive heart failure
No myocardial infarction within the past 6 months
LVEF at least 45% by echocardiogram or MUGA if received prior anthracycline or anthrapyrazole therapy

Other:

No prior hypersensitivity to trastuzumab, Chinese hamster ovary cell proteins, or any component of these products
No other medical illness that would preclude study
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy: