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

This study has been completed.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT00629499
First received: February 26, 2008
Last updated: August 29, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: nab paclitaxel
Drug: Cyclophosphamide
Drug: Trastuzumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Nanoparticle Albumin-Bound (Nab) Paclitaxel/Cyclophosphamide in Early-Stage Breast Cancer (With Trastuzumab in HER2 Positive Patients)

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • Tolerability of Adjuvant Nab Paclitaxel Using Weekly Dosing Schedule Assessed by Patient Survival, Disease Recurrence, and Treatment-related Toxicity. [ Time Frame: 18 Months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Disease-free Survival [ Time Frame: 18 Months ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: 18 Months ] [ Designated as safety issue: No ]

Enrollment: 63
Study Start Date: April 2008
Study Completion Date: September 2010
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
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)
Other Name: Abraxane
Drug: Cyclophosphamide
600 mg/m2 of IV cyclophosphamide
Other Name: Cytoxan
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.
Other Name: Herceptin

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00629499

Locations
United States, Florida
Watson Clinic Center for Cancer Care and Research
Lakeland, Florida, United States, 33805
Gulfcoast Oncology Associates
St. Petersburg, Florida, United States, 33705
United States, Kentucky
Consultants in Blood Disorders and Cancer
Louisville, Kentucky, United States, 40207
United States, Maine
Mercy Hospital
Portland, Maine, United States, 04101
United States, Maryland
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States, 20817
United States, Michigan
Grand Rapids Clinical Oncology Program
Grand Rapids, Michigan, United States, 49503
United States, Missouri
St. Louis Cancer Care
Chesterfield, Missouri, United States, 63017
United States, North Carolina
Cancer Care of Western North Carolina
Asheville, North Carolina, United States, 28801
United States, Tennessee
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37023
United States, Virginia
Peninsula Cancer Institute
Newport News, Virginia, United States, 23601
Sponsors and Collaborators
SCRI Development Innovations, LLC
Celgene Corporation
Investigators
Study Chair: John Hainsworth, MD SCRI Development Innovations, LLC
  More Information

Additional Information:
PubMed  This link exits the ClinicalTrials.gov site

Publications:
Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT00629499     History of Changes
Other Study ID Numbers: SCRI BRE 116
Study First Received: February 26, 2008
Results First Received: August 22, 2012
Last Updated: August 29, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by SCRI Development Innovations, LLC:
Early Stage Breast Cancer
Her2-positive
nab paclitaxel
cyclophosphamide
trastuzumab

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Trastuzumab
Paclitaxel
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on April 17, 2014