Clinical trial NCT00629499: Nanoparticle Albumin-Bound (Nab) Paclitaxel/Cyclophosphamide in Early-Stage Breast Cancer
Official title: Phase II Trial of Nanoparticle Albumin-Bound (Nab) Paclitaxel/Cyclophosphamide in Early-Stage Breast Cancer (With Trastuzumab in HER2 Positive Patients)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Early Stage Breast Cancer
Her2-positive
nab paclitaxel
cyclophosphamide
trastuzumab
Lead sponsor: SCRI Development Innovations, LLC
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
First posted: 2008-03-06
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants Who Remained Alive Without Evidence of Recurrence as a Measure of Tolerability of Adjuvant Nab Paclitaxel
timeFrame: 18 Months
Secondary outcomes:
measure: Disease-free Survival
timeFrame: 18 Months
measure: Overall Survival
timeFrame: 18 Months
Other outcomes:
Locations:
city: Lakeland
country: United States
facility: Watson Clinic Center for Cancer Care and Research
state: Florida
city: Saint Petersburg
country: United States
facility: Gulfcoast Oncology Associates
state: Florida
city: Louisville
country: United States
facility: Consultants in Blood Disorders and Cancer
state: Kentucky
city: Portland
country: United States
facility: Mercy Hospital
state: Maine
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders
state: Maryland
city: Grand Rapids
country: United States
facility: Grand Rapids Clinical Oncology Program
state: Michigan
city: Chesterfield
country: United States
facility: St. Louis Cancer Care
state: Missouri
city: Asheville
country: United States
facility: Cancer Care of Western North Carolina
state: North Carolina
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Newport News
country: United States
facility: Peninsula Cancer Institute
state: Virginia
Study officials:
affiliation: SCRI Development Innovations, LLC
name: John Hainsworth, MD
role: STUDY_CHAIR
References:
citation: 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.