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

This study is currently recruiting participants.
Verified October 2017 by Elizabeth Reed, MD, University of Nebraska
Sponsor:
ClinicalTrials.gov Identifier:
NCT01750073
First Posted: December 17, 2012
Last Update Posted: October 26, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Elizabeth Reed, MD, University of Nebraska
  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 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, may block tumor growth in different ways by targeting certain cells. 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 Estrogen Receptor Positive HER2/Neu Negative HER2/Neu Positive Invasive Breast Carcinoma Progesterone Receptor Negative Progesterone Receptor Positive Stage IA Breast Cancer Stage II Breast Cancer Stage IIA Breast Cancer Stage IIB Breast Cancer Stage III Breast Cancer Stage IIIA Breast Cancer Stage IIIB Breast Cancer Stage IIIC Breast Cancer Triple-Negative Breast Carcinoma Drug: Cyclophosphamide Drug: Doxorubicin Hydrochloride Other: Laboratory Biomarker Analysis Drug: Paclitaxel Radiation: Radiation Therapy Procedure: Therapeutic Conventional Surgery Biological: Trastuzumab Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (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 Elizabeth Reed, MD, University of Nebraska:

Primary Outcome Measures:
  • Overall incidence 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 ]
    Adverse events will be tallied for overall frequency (number and percentage of subjects), 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.

  • Overall severity of toxicities, graded according to the NCI CTCAE version 4.0 [ Time Frame: Up to 30 days after completion of study treatment ]
    Adverse events will be tallied for worst reported severity and relationship to study drugs. Serious adverse events will be summarized similarly. Listings of deaths, SAEs and 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.

  • 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: Up to 12 weeks (after the first 6 courses of treatment) ]
    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.


Secondary Outcome Measures:
  • Clinical complete response [ Time Frame: Up to 2 years ]
  • 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 ]
    The analysis will be based on Kaplan-Meier estimates. FFS 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 ]
    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.

  • 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 ]
    The analysis will be based on Kaplan-Meier estimates. OAS will be summarized overall and for HER+ and HER- subsets.


Estimated Enrollment: 125
Study Start Date: December 2012
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemotherapy, surgery, post-operative therapy)
See Detailed Description
Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
  • 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)
  • ADM
  • Adriacin
  • Adriamycin
  • Adriamycin Hydrochloride
  • Adriamycin PFS
  • Adriamycin RDF
  • ADRIAMYCIN, HYDROCHLORIDE
  • Adriamycine
  • Adriblastina
  • Adriblastine
  • Adrimedac
  • Chloridrato de Doxorrubicina
  • DOX
  • DOXO-CELL
  • Doxolem
  • Doxorubicin.HCl
  • Doxorubin
  • Farmiblastina
  • FI 106
  • FI-106
  • hydroxydaunorubicin
  • Rubex
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat
Radiation: Radiation Therapy
Undergo RT
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Irradiation
  • RADIATION
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
Procedure: Therapeutic Conventional Surgery
Undergo mastectomy or breast conserving surgery
Biological: Trastuzumab
Given IV
Other Names:
  • ABP 980
  • Anti-c-ERB-2
  • Anti-c-erbB2 Monoclonal Antibody
  • Anti-ERB-2
  • Anti-erbB-2
  • Anti-erbB2 Monoclonal Antibody
  • Anti-HER2/c-erbB2 Monoclonal Antibody
  • Anti-p185-HER2
  • c-erb-2 Monoclonal Antibody
  • HER2 Monoclonal Antibody
  • Herceptin
  • Herceptin Biosimilar PF-05280014
  • Herceptin Trastuzumab Biosimilar PF-05280014
  • MoAb HER2
  • Monoclonal Antibody c-erb-2
  • Monoclonal Antibody HER2
  • PF-05280014
  • rhuMAb HER2
  • RO0452317
  • Trastuzumab Biosimilar ABP 980
  • Trastuzumab Biosimilar PF-05280014

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, and then annually thereafter.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   19 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women with histologically proven invasive breast cancer without distant metastases; a clinical tumor classification of tumor size must be at least 1 cm with or without clinical pathologic evidence of positive nodes
  • 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
  • Absolute neutrophil count greater than or equal to 1,500/mcl
  • Platelet count equal to or greater than 150,000/mcl
  • 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
  • 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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01750073


Locations
United States, Nebraska
Nebraska Medicine-Bellevue Recruiting
Bellevue, Nebraska, United States, 68123
Contact: Elizabeth C. Reed    402-559-5749    ereed@unmc.edu   
Principal Investigator: Elizabeth C. Reed         
CHI Health Saint Francis Recruiting
Grand Island, Nebraska, United States, 68803
Contact: Mehmet S. Copur    308-398-6518    mcopur@sfmc-gi.org   
Principal Investigator: Mehmet S. Copur         
Nebraska Medicine-Village Pointe Cancer Center Recruiting
Omaha, Nebraska, United States, 68118
Contact: Elizabeth C. Reed    402-559-5749    ereed@unmc.edu   
Principal Investigator: Elizabeth C. Reed         
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
Contact: Elizabeth C. Reed    402-559-5749    ereed@unmc.edu   
Principal Investigator: Elizabeth C. Reed         
Sponsors and Collaborators
University of Nebraska
National Cancer Institute (NCI)
Investigators
Principal Investigator: Elizabeth Reed University of Nebraska
  More Information

Responsible Party: Elizabeth Reed, MD, Principal Investigator, University of Nebraska
ClinicalTrials.gov Identifier: NCT01750073     History of Changes
Other Study ID Numbers: 264-12
NCI-2012-01372 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
264-12 ( Other Identifier: University of Nebraska Medical Center )
P30CA036727 ( U.S. NIH Grant/Contract )
First Submitted: December 12, 2012
First Posted: December 17, 2012
Last Update Posted: October 26, 2017
Last Verified: October 2017

Additional relevant MeSH terms:
Carcinoma
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Paclitaxel
Liposomal doxorubicin
Albumin-Bound Paclitaxel
Cyclophosphamide
Doxorubicin
Trastuzumab
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents