Trastuzumab in Combination With Vinorelbine or Taxane-Based Chemotherapy in Patients With Metastatic Breast Cancer

Sponsor

Dana-Farber Cancer Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00146549

Collaborator

Massachusetts General Hospital (Other), Brigham and Women's Hospital (Other), North Shore Medical Center (Other), GlaxoSmithKline (Industry)

250

Enrollment

Locations

Duration (Months)

125

Patients Per Site

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to compare two different combinations of chemotherapy with trastuzumab as initial treatment for HER2 positive advanced breast cancer. Half of the patients will receive trastuzumab in combination with a taxane form of chemotherapy (either paclitaxel or docetaxel), while the other group will receive trastuzumab in combination with vinorelbine.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Stage IV Breast Cancer	Drug: Trastuzumab Drug: Vinorelbine Drug: Paclitaxel Drug: Docetaxel	Phase 3

Detailed Description

All patients will receive trastuzumab then be randomized into one of two arms. Arm A: Trastuzumab in combination with weekly vinorelbine and Arm B: Trastuzumab in combination with a weekly taxane-based regimen, either paclitaxel or docetaxel, chosen at the discretion of the investigator.
Treatment is administered on an outpatient basis. Trastuzumab is administered weekly. There is a one-time loading dose for the first week of the first cycle. For that initial treatment, only, the trastuzumab dose is 4mg/kg. The dose for all subsequent weekly trastuzumab treatments is 2mg/kg.
Arm A: vinorelbine is administered every week and the dose is adjusted based on the absolute neutrophil count for that week. Vinorelbine is given after trastuzumab.
Arm B: Either paclitaxel given weekly (dose bases on absolute neutrophil count) or docetaxel given on weeks 1,2,3,5,6,7 of each 8-week cycle (dose based upon absolute neutrophil count). Patients on paclitaxel will also receive dexamethasone, diphenhydramine and ranitidine to help prevent allergic or hypersensitivity reactions. Patients on docetaxel will receive dexamethasone to help reduce fluid retention or edema.
Every 8 weeks the patients cancer will be re-evaluated to see if the treatment is working. If the treatment appears to be working, treatment will continue. Standard radiological testing (x-rays, CT scan, radioactive drug scans, or MRI's) will be used to follow the disease treatment.
Heart function will be measured after 16 weeks to be sure it is safe to continue treatment.
Every 8 weeks, patients' will be asked to complete a brief written survey that asks about symptoms and side effects.
Patients' will remain on the treatment as long as there is no disease progression or unacceptable side effects.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Phase III Study of Trastuzumab (Herceptin) in Combination With Either Vinorelbine (Navelbine), or Taxane-based Chemotherapy in Patients With HER2 Overexpressing Metastatic Breast Cancer

Study Start Date :

Aug 1, 2001

Actual Primary Completion Date :

Aug 1, 2007

Actual Study Completion Date :

Dec 1, 2007

Outcome Measures

Primary Outcome Measures

To compare the overall response rate for patients receiving trastuzumab in combination with either vinorelbine or taxane-based chemotherapy. []

Secondary Outcome Measures

Characterization of the time to disease progression and time to treatment failure for patients receiving trastuzumab with either vinorelbine or taxane-based chemotherapy []
Characterization of side effects for both treatments []
analysis of quality of life for patients receiving either treatment. []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically or cytologically confirmed invasive breast cancer, with stage IV disease
Tumors must be HER2 overexpressing
Measurable disease, defined as a least one lesion that can be accurately measured in at least one dimension
18 years of age or older
Life expectancy of greater than 6 months
ECOG performance status of 0-2
ANC count > 1,500/mm3
Platelets > 100,000/mm3
Total bilirubin < 1.5 mg/dl
AST/ALT < 115 U/I
Creatinine < 2.0 mg/dl
Glucose < 200 mg/dl
LVEF > 50%

Exclusion Criteria:

Prior chemotherapy or prior trastuzumab therapy for metastatic breast cancer
Concurrent hormonal therapy, chemotherapy, or radiation treatments
Pregnant or lactating women
Known brain metastases or leptomeningeal carcinomatosis
History of grade 3 or 4 allergic reactions attributed to compounds of similar chemical or biologic composition to the agents in this study
Pre-existing neuropathy from any cause in excess of grade 1
Uncontrolled intercurrent illness
History of other non-breast cancer malignancy except for carcinoma in situ of the cervix or non-melanoma skin cancer
Patients taking macrolide antibiotics, ketoconazole, or AZT