Paclitaxel With or Without Trastuzumab in Treating Patients With or Without HER-2/Neu Breast Cancer That is Inoperable, Recurrent, or Metastatic

NCT ID: NCT00003440

Last Updated: 2013-06-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

580 participants

Study Classification

INTERVENTIONAL

Study Start Date

1998-07-31

Brief Summary

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This randomized phase III studies how well two different regimens of paclitaxel with or without trastuzumab works in treating patients with or without HER-2/Neu breast cancer that is inoperable, recurrent, or metastatic. Drugs used in chemotherapy, such as paclitaxel, 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. It is not yet known what regimen of paclitaxel is more effective with or without trastuzumab in treating patients with breast cancer.

Detailed Description

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PRIMARY OBJECTIVES:

I. To determine whether "dose dense" (DD) treatment with paclitaxel via weekly 1-hour infusion has a significantly higher response rate than "standard" (S) paclitaxel treatment, regardless of human epidermal growth factor receptor 2 (HER-2/neu) status and assignment to Herceptin (trastuzumab).

II. To determine if the addition of Herceptin to DD or S paclitaxel significantly improves the response rate as compared to DD or S paclitaxel alone for HER-2/neu non-overexpressing metastatic breast cancer (e.g., 0 or 1+).

III. To determine whether the addition of Herceptin to chemotherapy treatment modifies the quality of life experienced by patients with HER-2/neu non-overexpressing metastatic breast cancer.

IV. To determine whether the quality of life experienced by patients with metastatic breast cancer who have been treated with "standard" paclitaxel treatment differ from that of patients treated with "dose dense" paclitaxel treatment.

V. To correlate amplification and overexpression of the growth factor receptor ErbB2 by immunohistochemistry and fluorescent in-situ hybridization (FISH) with response rate, time to progression, and overall survival of patients with metastatic breast cancer treated with paclitaxel chemotherapy and paclitaxel + Herceptin.

VI. To correlate ErbB2 shed extracellular domain (ECD) with response rate, time to progression, and overall survival of patients with metastatic breast cancer treated with different doses and schedules of paclitaxel and paclitaxel + Herceptin. In addition, to follow patterns of ErbB2/ECD after treatment and upon relapse.

SECONDARY OBJECTIVES:

I. To evaluate time to progression and survival of patients with HER-2 overexpressing metastatic breast cancer treated with either DD or S paclitaxel plus weekly Herceptin.

II. To evaluate time to progression and survival of patients with HER-2 non-overexpressing metastatic breast cancer treated with either DD or S paclitaxel alone or DD or S paclitaxel plus weekly Herceptin.

III. To evaluate cardiac toxicity as measured by changes in LVEF from baseline to follow-up measurements.

OUTLINE; Patients are assigned to 1 of 2 treatment groups.

GROUP I (HER2/neu non-overexpressors): Patients are randomized to 1 of 4 treatment arms.

ARM A: Patients receive paclitaxel intravenously (IV) over 3 hours every 3 weeks.

ARM B: Patients receive paclitaxel IV over 1 hour weekly.

ARM C: Patients receive paclitaxel as in Arm A. Patients also receive trastuzumab IV weekly.

ARM D: Patients receive paclitaxel as in Arm B and trastuzumab as in Arm C.

GROUP II (HER2/neu overexpression): Patients are assigned to 1 of 2 treatment arms.

ARM E: Patients receive paclitaxel and trastuzumab as in Arm C.

ARM F: Patients receive paclitaxel and trastuzumab as in Arm D.

In all arms, courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

After the completion of study treatment, patients are followed up periodically for up to 5 years.

Conditions

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HER2-negative Breast Cancer HER2-positive Breast Cancer Recurrent Breast Cancer Stage IIIC Breast Cancer Stage IV Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Arm A (paclitaxel)

Patients receive paclitaxel intravenously (IV) over 3 hours every 3 weeks.

Group Type EXPERIMENTAL

paclitaxel

Intervention Type DRUG

Given IV over 1 hour or 3 hours

quality-of-life assessment

Intervention Type PROCEDURE

Ancillary studies

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Arm B (paclitaxel)

Patients receive paclitaxel IV over 1 hour weekly.

Group Type ACTIVE_COMPARATOR

paclitaxel

Intervention Type DRUG

Given IV over 1 hour or 3 hours

quality-of-life assessment

Intervention Type PROCEDURE

Ancillary studies

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Arm C (paclitaxel, trastuzumab)

Patients receive paclitaxel as in Arm I. Patients also receive trastuzumab IV weekly.

Group Type EXPERIMENTAL

paclitaxel

Intervention Type DRUG

Given IV over 1 hour or 3 hours

trastuzumab

Intervention Type BIOLOGICAL

Given IV

quality-of-life assessment

Intervention Type PROCEDURE

Ancillary studies

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Arm D (paclitaxel, trastuzumab)

Patients receive paclitaxel as in Arm II and trastuzumab as in Arm III.

Group Type ACTIVE_COMPARATOR

paclitaxel

Intervention Type DRUG

Given IV over 1 hour or 3 hours

trastuzumab

Intervention Type BIOLOGICAL

Given IV

quality-of-life assessment

Intervention Type PROCEDURE

Ancillary studies

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Am E (paclitaxel, trastuzumab)

Patients receive paclitaxel and trastuzumab as in Arm C.

Group Type EXPERIMENTAL

paclitaxel

Intervention Type DRUG

Given IV over 1 hour or 3 hours

trastuzumab

Intervention Type BIOLOGICAL

Given IV

quality-of-life assessment

Intervention Type PROCEDURE

Ancillary studies

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Arm F (paclitaxel, trastuzumab)

Patients receive paclitaxel and trastuzumab as in Arm D.

Group Type ACTIVE_COMPARATOR

paclitaxel

Intervention Type DRUG

Given IV over 1 hour or 3 hours

trastuzumab

Intervention Type BIOLOGICAL

Given IV

quality-of-life assessment

Intervention Type PROCEDURE

Ancillary studies

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Interventions

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paclitaxel

Given IV over 1 hour or 3 hours

Intervention Type DRUG

trastuzumab

Given IV

Intervention Type BIOLOGICAL

quality-of-life assessment

Ancillary studies

Intervention Type PROCEDURE

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

Other Intervention Names

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Anzatax Asotax TAX Taxol anti-c-erB-2 Herceptin MOAB HER2 quality of life assessment

Eligibility Criteria

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Inclusion Criteria

* Histologically confirmed adenocarcinoma of the female breast which is inoperable, recurrent or metastatic
* HER-2/neu status must be known at the time of protocol registration; HER-2/neu assessment will be based on FISH analysis of either the primary tumor or a metastatic site; a scoring of 0 or 1+ by immunohistochemistry (IHC) is considered negative; 2+ is considered negative unless confirmed by FISH positivity, in which case it should be considered positive; 3+ by IHC is considered positive; for centers using FISH only, a positive FISH assay by itself is sufficient to determine HER-2 positivity
* Patients with the following prior therapy are eligible:

* Patients with 0-1 prior chemotherapy regimens for metastatic or locally advanced breast cancer, with the following exception: no prior taxane for metastatic/locally advanced breast cancer
* Patients with 0-1 prior chemotherapy regimens in the adjuvant setting; if adjuvant regimen included a taxane, patient must have been disease free for at least 12 months from completion of adjuvant therapy until relapse
* Patients must be \> 2 weeks from prior surgery, other than simple biopsy or placement of venous access device; patients must be \> 4 weeks from prior chemotherapy; patients must be \>6 weeks from nitrosoureas, melphalan, or mitomycin

* Patients must be \> 4 weeks from prior hormonal therapy unless tumor measurements document clear progression while on treatment; if progression is documented and toxicity from hormonal regimen has resolved, patients may be placed on study \> 1 week from prior hormonal therapy
* Prior Herceptin therapy is not allowed
* Patients with central nervous system metastases are eligible only if the patient has completed cranial irradiation at least 6 months prior, is currently asymptomatic, and is not currently receiving corticosteroids for this condition; patients with leptomeningeal carcinoma (carcinomatous meningitis) are not eligible
* MESURABLE DISEASE: Any mass reproducibly measurable in two perpendicular dimensions, examples include:

* Pulmonary nodules
* Hepatic lesions
* Skin nodules (if two measurements can be assigned)
* Lymph nodes
* The following lesions do not qualify as measurable:

* Central nervous system (CNS) lesions
* Bone disease only; lytic lesions should be documented and followed
* Lymphangitic pulmonary metastases (patients with lymphangitic metastases are eligible if there are other sites of metastatic disease which can be measured)
* Lesions which have been irradiated unless there is definite documentation of progression since radiotherapy
* A baseline assessment of left ventricular ejection fraction within 8 weeks of registration is required (echocardiogram or resting multi gated acquisition scan \[MUGA\] (radionuclide cineangiography \[RNCA\]) nuclear scintigraphy); patients with a left ventricular ejection fraction (LVEF) \< 45% are ineligible
* Granulocytes \>= 1500/ul
* Platelet count \>= 100,000/ul
* Creatinine =\< 2.0 mg/dl
* Bilirubin within institutional normal limits
* Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\])
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Andrew Seidman

Role: PRINCIPAL_INVESTIGATOR

Cancer and Leukemia Group B

Locations

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Cancer and Leukemia Group B

Chicago, Illinois, United States

Site Status

Countries

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United States

Other Identifiers

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CALGB-9840

Identifier Type: -

Identifier Source: secondary_id

U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-02792

Identifier Type: -

Identifier Source: org_study_id

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