Nanoparticle Albumin-Bound (Nab) Paclitaxel/Cyclophosphamide in Early-Stage Breast Cancer

NCT ID: NCT00629499

Last Updated: 2021-11-24

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

63 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-04-30

Study Completion Date

2010-09-30

Brief Summary

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This is a non-randomized, Phase II study. Efficacy is not a primary endpoint in this study; however, progression-free survival will be followed and determined for the patients in this study. Approximately 50 patients are planned to be enrolled in this study.

Detailed Description

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Given the favorable activity demonstrated in a trial using the taxane docetaxel in combination with cyclophosphamide, we propose a Phase II trial of 4 cycles of weekly nab paclitaxel combined with cyclophosphamide. The favorable toxicity profile for weekly nab paclitaxel, in addition to its demonstrated superiority over standard paclitaxel in early-stage breast cancer, makes it an ideal taxane to evaluate in this setting. In this study, nab paclitaxel will be administered once weekly, in combination with q3wk cyclophosphamide. By using this combination therapy method, the goal of this study is to maximize the opportunity to demonstrate improved tolerability of adjuvant nab paclitaxel using a weekly dosing schedule in combination with q3wk cyclophosphamide.

In this study, patients who demonstrate FISH or IHC3+ HER2 positivity and adequate cardiac function will also receive treatment with trastuzumab in addition to the nab paclitaxel / cyclophosphamide combination therapy. Trastuzumab will be administered IV using an 8 mg/kg loading dose on Day 1 of the treatment period. If no toxicity occurs, subsequent doses of trastuzumab will be administered IV as a 6 mg/kg dose approximately every 21 days for a total of 52 weeks (thus, maintenance therapy with trastuzumab will continue after the 12-week period of combination therapy with nab paclitaxel/cyclophosphamide/trastuzumab has ended).

Conditions

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Breast Cancer

Keywords

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Early Stage Breast Cancer Her2-positive nab paclitaxel cyclophosphamide trastuzumab

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Intervention

100 mg/m2 of intravenous (IV) nab paclitaxel weekly (i.e., on Days 1, 8, and 15 of each 3 week treatment cycle) in combination with 600 mg/m2 of IV cyclophosphamide once every 3 weeks for 4 cycles (i.e., a total treatment period of 12 weeks \[84 days\]). Patients with fluorescence in situ hybridization (FISH) HER2+ or IHC3+ breast cancer will also receive treatment with trastuzumab in addition to the nab paclitaxel / cyclophosphamide combination therapy. Maintenance therapy with trastuzumab will continue (for the HER2+ patients who are receiving trastuzumab) after the 12-week treatment period with combination nab paclitaxel/cyclophosphamide/trastuzumab. The total treatment time for trastuzumab will be 52 weeks rather than only 12 weeks.

Group Type EXPERIMENTAL

nab paclitaxel

Intervention Type DRUG

100 mg/m2 of intravenous (IV) nab paclitaxel weekly (i.e., on Days 1, 8, and 15 of each 3 week treatment cycle)

Cyclophosphamide

Intervention Type DRUG

600 mg/m2 of IV cyclophosphamide

Trastuzumab

Intervention Type DRUG

8 mg/kg loading dose of IV trastuzumab will be administered on Day 1, followed by doses of 6 mg/kg IV trastuzumab once every 3 weeks.

Interventions

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nab paclitaxel

100 mg/m2 of intravenous (IV) nab paclitaxel weekly (i.e., on Days 1, 8, and 15 of each 3 week treatment cycle)

Intervention Type DRUG

Cyclophosphamide

600 mg/m2 of IV cyclophosphamide

Intervention Type DRUG

Trastuzumab

8 mg/kg loading dose of IV trastuzumab will be administered on Day 1, followed by doses of 6 mg/kg IV trastuzumab once every 3 weeks.

Intervention Type DRUG

Other Intervention Names

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Abraxane Cytoxan Herceptin

Eligibility Criteria

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Inclusion Criteria

* Histologically confirmed invasive adenocarcinoma of the breast or inflammatory breast cancer, with an interval between definitive breast surgery and study registration of \<60 days.
* Definitive surgical treatment must be either mastectomy or breast-conserving therapy with axillary lymph node dissection for operable breast cancer (pT1 4 \[including inflammatory breast cancer\], pN0 3, and M0). Margins of resected specimen from definitive surgery must be histologically free of invasive adenocarcinoma and ductal carcinoma in situ (DCIS). Lobular carcinoma in-situ does not count as a positive margin.
* Patients with ≥1 axillary lymph node containing metastatic adenocarcinoma measuring \>0.2 mm, OR lymph node-negative patients with high-risk features
* Patients with HER2/neu positive or negative tumors (HER2 positivity must be documented by FISH positivity or IHC 3+).
* Patients who are to receive trastuzumab must have normal cardiac function (MUGA \[cardiac ejection fraction \>50%, or greater than or equal to the institutional lower limit of normal\], or echocardiogram \[ECHO\] within institutional normal limits).
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2.
* Patients who are either chemotherapy naïve, or who have received prior chemotherapy \>5 years ago.
* Patients with previous invasive cancers (including breast cancer) eligible only if treated \>5 years prior to entering this study, and show no evidence of recurrent disease.
* Adequate bone marrow function
* Adequate liver function,
* Adequate renal function,
* Patients of childbearing potential must use an effective method of contraception that is acceptable to their study physician from the time of signing informed consent until at least 3 months after the last dose of protocol treatment, and must have a negative pre study serum pregnancy test.
* Pre-existing peripheral neuropathy must be less than or equal to grade 1 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 criteria.
* MammoSite® brachytherapy radiation accepted when performed immediately following surgery and prior to receiving chemotherapy.

Exclusion Criteria

* Patients who are pregnant or breastfeeding.
* M1 metastatic disease.
* Patients requiring neoadjuvant chemotherapy.
* Life expectancy of greater than 6 months.
* History of cardiac disease, with a New York Heart Association (NYHA) Class II or greater CHF
* Myocardial infarction (MI) or unstable angina in the past 12 months prior to Day 1 of treatment, serious arrhythmias requiring medication for treatment, any history of stroke or transient ischemic attack at any time, clinically significant peripheral vascular disease, or evidence of a bleeding diathesis or coagulopathy.
* Any investigational agent within 30 days of receiving the first dose of study drug.
* Treatment with prior trastuzumab or bevacizumab therapy.
* Concurrent treatment with any other anti-cancer therapy is not permitted.
* History of significant psychiatric disorders.
* History of active, uncontrolled infection.
* A serious, non-healing wound, ulcer, or bone fracture.
* Any other diseases, metabolic dysfunction, findings from a physical examination, or clinical laboratory test results that give reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, that may affect the interpretation of the results or that renders the patient at high risk from treatment complications.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Celgene Corporation

INDUSTRY

Sponsor Role collaborator

SCRI Development Innovations, LLC

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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John Hainsworth, MD

Role: STUDY_CHAIR

SCRI Development Innovations, LLC

Locations

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Watson Clinic Center for Cancer Care and Research

Lakeland, Florida, United States

Site Status

Gulfcoast Oncology Associates

St. Petersburg, Florida, United States

Site Status

Consultants in Blood Disorders and Cancer

Louisville, Kentucky, United States

Site Status

Mercy Hospital

Portland, Maine, United States

Site Status

Center for Cancer and Blood Disorders

Bethesda, Maryland, United States

Site Status

Grand Rapids Clinical Oncology Program

Grand Rapids, Michigan, United States

Site Status

St. Louis Cancer Care

Chesterfield, Missouri, United States

Site Status

Cancer Care of Western North Carolina

Asheville, North Carolina, United States

Site Status

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Site Status

Peninsula Cancer Institute

Newport News, Virginia, United States

Site Status

Countries

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United States

References

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Yardley D, Burris H 3rd, Peacock N, Raefsky E, Melnik M, Inhorn R, Shipley D, Hainsworth J. A pilot study of adjuvant nanoparticle albumin-bound (nab) paclitaxel and cyclophosphamide, with trastuzumab in HER2-positive patients, in the treatment of early-stage breast cancer. Breast Cancer Res Treat. 2010 Sep;123(2):471-5. doi: 10.1007/s10549-010-1047-0. Epub 2010 Jul 24.

Reference Type RESULT
PMID: 20658263 (View on PubMed)

Related Links

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Other Identifiers

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SCRI BRE 116

Identifier Type: -

Identifier Source: org_study_id