Paclitaxel With or Without Trastuzumab in Treating Patients With or Without HER-2/Neu Breast Cancer That is Inoperable, Recurrent, or Metastatic
This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003440
First received: November 1, 1999
Last updated: June 3, 2013
Last verified: June 2013
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
HER2-negative Breast Cancer HER2-positive Breast Cancer Recurrent Breast Cancer Stage IIIC Breast Cancer Stage IV Breast Cancer |
Drug: paclitaxel Biological: trastuzumab Procedure: quality-of-life assessment Other: laboratory biomarker analysis |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment |
| Official Title: | A Phase III Study of Paclitaxel Via Weekly 1 Hour Infusion Versus Standard 3 Hour Infusion Every 3 Weeks With Herceptin (Trastuzumab) (NSC #688097) in the Treatment of Patients With/Without HER-2/Neu-Overexpressing Metastatic Breast Cancer |
Resource links provided by NLM:
Further study details as provided by National Cancer Institute (NCI):
Primary Outcome Measures:
- Response rate (complete response [CR]) and partial response [PR]) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Multivariate logistic regression will be used to relate patient characteristics and pretreatment clinical variables with tumor response (complete or partial). Interim analyses will use a chi square statistic to compare response incidence by treatment arm with two-sided bounds constructed from the O'Brien-Fleming approach
Secondary Outcome Measures:
- Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Kaplan-Meier curves will be plotted for each of the arms. Sets of curves will be compared using the logrank statistic. A Cox proportional hazards regression model will be used to relate length of survival with paclitaxel dose schedule, HER-2/neu status, Herceptin use (for HER-2/neu negatives), number of sites of metastases at baseline, ER status,
- Time to disease progression: [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Kaplan-Meier curves will be plotted for each combination of therapy. Sets of curves will be compared using the logrank statistic. A Cox proportional hazards regression model will be used to relate length of survival with paclitaxel dose schedule, HER-2/neu status, Herceptin use (for HER-2/neu negatives), number of sites of metastases at baseline, ER status, CALGB performance status, prior adjuvant chemotherapy, and prior radiotherapy.
- Duration of response [ Time Frame: Length of time between response and disease progression, assessed up to 5 years ] [ Designated as safety issue: No ]For patients who achieve response within each arm, Kaplan-Meier curves will be used to estimate probability distributions for duration of response. Distributions will be compared using the logrank statistic.
- Cardiac toxicity as measured by changes in LVEF [ Time Frame: From baseline to up to 5 years ] [ Designated as safety issue: Yes ]Cardiac toxicity will be evaluated using multivariate logistic regression.
- Toxicity as assessed by CALGB Expanded Common Toxicity Criteria [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]Toxicity frequency will be tabulated by most severe occurrence.
- Change in quality of life (QOL) [ Time Frame: From baseline to up to 9 months ] [ Designated as safety issue: No ]EORTC Breast Cancer Module QLQ-BR23, Changes in Function (C-616), Centers for Epidemiologic Studies-Depression (CES-d) Short Form (C-617), MOS Social Support Questionnaire (C-249), Spirituality Subscale (C-613) will be used to assess QOL. Multiple regression will be used to examine whether sociodemographic characteristics (age, gender, education, marital status, ethnicity, employment status); treatment (chemotherapy dose, Herceptin usage); clinical factors (HER2 status, performance status); and pre-treatment QOL, social support and spirituality, are significant predictors of survival.
- Correlation between ErbB2 and response to treatment [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Correlation will be assessed using contingency tables for two dichotomous variables, point biserial correlation for one dichotomous and one continuous variable and Pearson correlation for two dichotomous variables.
| Enrollment: | 580 |
| Study Start Date: | July 1998 |
| Primary Completion Date: | July 2004 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm A (paclitaxel)
Patients receive paclitaxel intravenously (IV) over 3 hours every 3 weeks.
|
Drug: paclitaxel
Given IV over 1 hour or 3 hours
Other Names:
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: laboratory biomarker analysis
Correlative studies
|
|
Active Comparator: Arm B (paclitaxel)
Patients receive paclitaxel IV over 1 hour weekly.
|
Drug: paclitaxel
Given IV over 1 hour or 3 hours
Other Names:
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: laboratory biomarker analysis
Correlative studies
|
|
Experimental: Arm C (paclitaxel, trastuzumab)
Patients receive paclitaxel as in Arm I. Patients also receive trastuzumab IV weekly.
|
Drug: paclitaxel
Given IV over 1 hour or 3 hours
Other Names:
Biological: trastuzumab
Given IV
Other Names:
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: laboratory biomarker analysis
Correlative studies
|
|
Active Comparator: Arm D (paclitaxel, trastuzumab)
Patients receive paclitaxel as in Arm II and trastuzumab as in Arm III.
|
Drug: paclitaxel
Given IV over 1 hour or 3 hours
Other Names:
Biological: trastuzumab
Given IV
Other Names:
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: laboratory biomarker analysis
Correlative studies
|
|
Experimental: Am E (paclitaxel, trastuzumab)
Patients receive paclitaxel and trastuzumab as in Arm C.
|
Drug: paclitaxel
Given IV over 1 hour or 3 hours
Other Names:
Biological: trastuzumab
Given IV
Other Names:
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: laboratory biomarker analysis
Correlative studies
|
|
Active Comparator: Arm F (paclitaxel, trastuzumab)
Patients receive paclitaxel and trastuzumab as in Arm D.
|
Drug: paclitaxel
Given IV over 1 hour or 3 hours
Other Names:
Biological: trastuzumab
Given IV
Other Names:
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: laboratory biomarker analysis
Correlative studies
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Criteria
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])
Contacts and Locations More Information
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00003440 History of Changes |
| Other Study ID Numbers: | NCI-2012-02792, CALGB-9840, U10CA031946 |
| Study First Received: | November 1, 1999 |
| Last Updated: | June 3, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Paclitaxel Trastuzumab Tubulin Modulators |
Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents, Phytogenic Antineoplastic Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on June 18, 2013