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Paclitaxel and Cyclophosphamide With or Without Trastuzumab Before Surgery in Treating Patients With Previously Untreated Stage I-III Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by University of Nebraska
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Nebraska
ClinicalTrials.gov Identifier:
NCT01750073
First received: December 12, 2012
Last updated: NA
Last verified: December 2012
History: No changes posted
  Purpose

This phase II trial studies the side effects and how well giving paclitaxel and cyclophosphamide with or without trastuzumab before surgery works in treating patients with previously untreated stage I-III breast cancer. Drugs used in chemotherapy, such as paclitaxel and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving combination chemotherapy with or without trastuzumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed


Condition Intervention Phase
Estrogen Receptor-negative Breast Cancer
Estrogen Receptor-positive Breast Cancer
HER2-negative Breast Cancer
HER2-positive Breast Cancer
Progesterone Receptor-negative Breast Cancer
Progesterone Receptor-positive Breast Cancer
Stage IA Breast Cancer
Stage II Breast Cancer
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Triple-negative Breast Cancer
Drug: paclitaxel
Drug: cyclophosphamide
Biological: trastuzumab
Procedure: therapeutic conventional surgery
Radiation: radiation therapy
Drug: doxorubicin hydrochloride
Other: laboratory biomarker analysis
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: A Phase II Study of Neoadjuvant Chemotherapy With and Without Trastuzumab in Patients With Breast Cancer

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • pCR, determined from the surgical specimen and is defined as the absence of invasive carcinoma in both the breast and axilla at microscopic examination of the resection specimen, regardless of the presence of carcinoma in situ [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    The pCR rates and exact one-sided 80% confidence intervals will be calculated. The primary analysis is based on the full analysis set (all treated patients). The pCR rates will be summarized overall and for HER+ and HER- subsets.

  • Overall incidence and severity of toxicities, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]
    Adverse events will be tallied for overall frequency (number and percentage of subjects), worst reported severity, and relationship to study drugs. Serious adverse events will be summarized similarly. Listings of deaths, serious adverse events (SAEs) and adverse events (AEs) leading to early termination of study treatment or premature withdrawal from study will also be provided. Analyses will be reported overall and for HER+ and HER- subsets.


Secondary Outcome Measures:
  • Clinical complete response [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Failure-free survival (FFS) [ Time Frame: The time from the date of administration of study drug to the date of first appearance of tumor lesions by imaging, or death, assessed up to 2 years ] [ Designated as safety issue: No ]
    The analysis will be based on Kaplan-Meier estimates. FFS will be summarized overall and for HER+ and HER- subsets.

  • Overall survival (OAS) [ Time Frame: The time from the date of the date of administration of study drug to the date of death from any cause, assessed up to 2 years ] [ Designated as safety issue: No ]
    The analysis will be based on Kaplan-Meier estimates. OAS will be summarized overall and for HER+ and HER- subsets.

  • Identification of gene expression profile signatures that correlate with clinical response as measured by pCR [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    The number of the identified mutated genes, the frequency of each gene being validated by reverse transcriptase-polymerase chain reaction (RT-PCR)/Sanger sequencing method, and the functions of these identified genes will be descriptively summarized.


Estimated Enrollment: 125
Study Start Date: December 2012
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemotherapy, surgery, post-operative therapy)
See Detailed Description
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Biological: trastuzumab
Given IV
Other Names:
  • anti-c-erB-2
  • Herceptin
  • MOAB HER2
Procedure: therapeutic conventional surgery
Undergo mastectomy or breast conserving surgery
Radiation: radiation therapy
Undergo RT
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the toxicities and tolerability of a neoadjuvant dose-dense regimen cyclophosphamide and paclitaxel with or without trastuzumab/radiation therapy (as clinically indicated) in patients with newly diagnosed stage T1cN0 and II-III breast cancer; followed by maintenance trastuzumab in human epidermal growth factor receptor 2 (HER2) positive OR Adriamycin (doxorubicin hydrochloride) followed by radiation therapy (RT) in stage II-III triple negative HER2 (-), estrogen receptor (ER) (-), progesterone receptor (PR) (-) stage T1cN0 and II-III breast cancer patients.

II. To determine the pathological complete response rate (pCR) of this treatment regimen.

III. To identify possible gene expression profile signatures from whole genome array analysis that correlate with clinical response/resistance to chemotherapy as measured by pathologic complete response rate (pCR).

OUTLINE:

NEOADJUVANT THERAPY: Patients receive paclitaxel intravenously (IV) over 3 hours and cyclophosphamide IV over 1 hour on day 1. Patients with HER2-positive cancer also receive trastuzumab IV over 30 minutes on day 1. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients without metastasis undergo mastectomy or breast conserving surgery 4-8 weeks later.

POST-SURGERY/SYSTEMIC THERAPY:

HER2-POSITIVE PATIENTS: Patients receive standard radiation therapy. Patients also receive trastuzumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.

ER/PR POSITIVE PATIENTS: Patients receive standard adjuvant hormonal or endocrine therapy.

STAGE T1cN0 TRIPLE NEGATIVE PATIENTS: Patients receive standard radiation therapy.

STAGE II-III TRIPLE NEGATIVE PATIENTS: Patients receive doxorubicin hydrochloride IV over 15 minutes on day 1. Treatment repeats every 14 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients also receive standard radiation therapy.

After completion of study treatment, patients are followed up every 3 months for 2 years.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women with histologically proven invasive breast cancer without distant metastases and lymph node negative and a clinical tumor classification of T1cN0 or stage II-III
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • At least one lesion that can be accurately measured in two dimensions utilizing mammogram, ultrasound, or magnetic resonance imaging (MRI) images to define specific size and validate complete clinical and pathologic response
  • Patients who received radiation therapy > 5 years ago for malignancies other than breast cancer and whose radiation therapy field is not overlapping with the 20% isodose line of current radiation field are eligible, provided that radiation therapy was completed > 5 years ago and that there is no evidence of the second malignancy at the time of study entry
  • All malignant disease must be able to be encompassed within a single irradiation field
  • Absolute neutrophil count greater than or equal to 1,500/mcl
  • Platelet count equal to or greater than 150,000/mcl
  • Hemoglobin > 11gm/dl
  • Alkaline phosphatase equal or less than 1.5 times the upper limit of normal (ULN)
  • Total bilirubin equal to or less than 1.5 times the ULN
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) no greater than 1.5 times the ULN
  • Creatinine less than 1.5 times the ULN
  • All included patients must have normal cardiac function as defined by an ejection fraction of > 50% and no decrease in wall motion by echocardiogram
  • The patient must be aware of the neoplastic nature of his/her disease and willingly provide written, informed consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts
  • Women of reproductive potential must be non-pregnant and non-nursing and must agree to employ an effective barrier method of birth control throughout the study and for up to 6 months following treatment
  • Women of child-bearing potential must have a negative pregnancy test within 7 days of initiating study; (no childbearing potential is defined as age 55 years or older and no menses for two years or any age with surgical removal of the uterus and/or both ovaries)

Exclusion Criteria:

  • Any patient with inflammatory breast cancer or stage IV or confirmed metastatic disease
  • Patients who have had any prior chemotherapy, or endocrine therapy for the treatment of breast cancer or any other cancer
  • Patients who cannot undergo surgery
  • Patients with a known or documented anaphylactic reaction or allergy to any of chemotherapy agents used in this protocol, or to antiemetics appropriate for administration in conjunction with protocol-directed therapy
  • Uncontrolled inter-current illness including, but not limited to ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure, unstable angina pectoris, or serious, uncontrolled cardiac arrhythmia, that might jeopardize the ability of the patient to receive the therapy program outlined in this protocol with reasonable safety
  • Patients with preexisting grade II peripheral neuropathy
  • Pregnant and nursing women are excluded from this study because the chemotherapy agents and radiation therapy all have the potential for teratogenic or abortifacient effects
  • Patients with prior malignancy will be excluded except for adequately treated basal cell or squamous cell skin cancer, adequately treated noninvasive carcinomas
  • Inability to cooperate with treatment protocol
  • Patients with known human immunodeficiency virus (HIV) infection, infectious hepatitis, type A, B or C, active hepatitis, or hepatic insufficiency
  • Patients may not be receiving or have received any other investigational agents during/or within 1 month prior
  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
  • Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01750073

Contacts
Contact: Mary Mailliard, RN BSN OCN 402-559-5582 mjmailli@unmc.edu
Contact: Lisa Houdesheldt, BS CCRP 402-559-4596 lhoudesheldt@unmc.edu

Locations
United States, Nebraska
Saint Francis Medical Center Recruiting
Grand Island, Nebraska, United States, 68803
Contact: Mehmet S. Copur, M.D.    308-398-6518    mcopur@sfmc-gi.org   
Contact: Clinical Research Staff    308-398-6518    clinicaltrials@sfmc-gi.org   
Principal Investigator: Mehmet S. Copur, M.D.         
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198-7830
Contact: Elizabeth C. Reed, M.D.    402-559-5388    ereed@unmc.edu   
Contact: Mary J. Mailliard, RN BSN OCN    402-559-5582    mjmailli@unmc.edu   
Principal Investigator: Elizabeth C. Reed         
Sponsors and Collaborators
University of Nebraska
Investigators
Principal Investigator: Elizabeth Reed University of Nebraska
  More Information

No publications provided

Responsible Party: University of Nebraska
ClinicalTrials.gov Identifier: NCT01750073     History of Changes
Other Study ID Numbers: 264-12, NCI-2012-01372, P30CA036727
Study First Received: December 12, 2012
Last Updated: December 12, 2012
Health Authority: United States: Institutional Review Board

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

ClinicalTrials.gov processed this record on November 25, 2014