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

Breast Cancer Clinical Trial

Official title:

Phase II Trial of Nanoparticle Albumin-Bound (Nab) Paclitaxel/Cyclophosphamide in Early-Stage Breast Cancer (With Trastuzumab in HER2 Positive Patients)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00629499
• Other study ID #: SCRI BRE 116
• Status: Completed
• Phase: Phase 2
• Start date: April 2008
• Est. completion date: September 2010

Study information

• Verified date: November 2021
• Source: SCRI Development Innovations, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: September 2010
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

• Patients with bilateral, synchronous breast cancer, provided that one primary tumor meets the inclusion criteria.

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• 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)
• Cyclophosphamide
600 mg/m2 of IV cyclophosphamide
• 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.

Locations

Country	Name	City	State
United States	Cancer Care of Western North Carolina	Asheville	North Carolina
United States	Center for Cancer and Blood Disorders	Bethesda	Maryland
United States	St. Louis Cancer Care	Chesterfield	Missouri
United States	Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan
United States	Watson Clinic Center for Cancer Care and Research	Lakeland	Florida
United States	Consultants in Blood Disorders and Cancer	Louisville	Kentucky
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Peninsula Cancer Institute	Newport News	Virginia
United States	Mercy Hospital	Portland	Maine
United States	Gulfcoast Oncology Associates	Saint Petersburg	Florida

Sponsors (2)

Lead Sponsor	Collaborator
SCRI Development Innovations, LLC	Celgene Corporation

Country where clinical trial is conducted

United States, 

References & Publications (1)

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-s — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Remained Alive Without Evidence of Recurrence as a Measure of Tolerability of Adjuvant Nab Paclitaxel		18 Months
Secondary	Disease-free Survival	Number of participants that are disease free at 18th month	18 Months
Secondary	Overall Survival	Number of participants that are alive at 18th month	18 Months

External Links

•   PubMed