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

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: nab paclitaxel; Drug: Cyclophosphamide; Drug: Trastuzumab

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).

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Lakeland, Florida, United States, 33805
      • Watson Clinic Center for Cancer Care and Research
    • Saint Petersburg, Florida, United States, 33705
      • Gulfcoast Oncology Associates
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Consultants in Blood Disorders and Cancer
  • Maine
    • Portland, Maine, United States, 04101
      • Mercy Hospital
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Center for Cancer and Blood Disorders
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Grand Rapids Clinical Oncology Program
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • St. Louis Cancer Care
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Cancer Care of Western North Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37023
      • Tennessee Oncology, PLLC
  • Virginia
    • Newport News, Virginia, United States, 23601
      • Peninsula Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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 Names: Abraxane; Drug: Cyclophosphamide; 600 mg/m2 of IV cyclophosphamide; Other Names: 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 Names: Herceptin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Who Remained Alive Without Evidence of Recurrence as a Measure of Tolerability of Adjuvant Nab Paclitaxel	18 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free Survival	Number of participants that are disease free at 18th month	18 Months
Overall Survival	Number of participants that are alive at 18th month	18 Months

Collaborators and Investigators

• Sponsor: SCRI Development Innovations, LLC
• Collaborators: Celgene Corporation
• Investigators: Study Chair: John Hainsworth, MD, SCRI Development Innovations, LLC

Publications and helpful links

General Publications

• 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.

Helpful Links

• PubMed

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: February 26, 2008
• First Submitted That Met QC Criteria: February 26, 2008
• First Posted (Estimate): March 6, 2008

Study Record Updates

• Last Update Posted (Actual): November 24, 2021
• Last Update Submitted That Met QC Criteria: November 23, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: cyclophosphamide; trastuzumab; Early Stage Breast Cancer; Her2-positive; nab paclitaxel
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Cyclophosphamide; Paclitaxel; Trastuzumab
• Other Study ID Numbers: SCRI BRE 116