Estrogen Receptor NegativePhase 2NCT01750073
Paclitaxel & Cyclophosphamide With or Without Trastuzumab Before Surgery in Treating Previously Untreated Breast Cancer
A Phase 2 study testing Cyclophosphamide, Doxorubicin Hydrochloride and Laboratory Biomarker Analysis in people with Estrogen Receptor Negative and Estrogen Receptor Positive, run by University of Nebraska at 4 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 19 years and older, women only
- Conditions the study is for
- Estrogen Receptor Negative, Estrogen Receptor Positive, HER2/Neu Negative
- What is being tested?
- Cyclophosphamide, Doxorubicin Hydrochloride and Laboratory Biomarker Analysis
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 92 participants
- Where
- 4 sitesUnited States
- Study dates
- 7 Dec 2012to 24 Nov 2025
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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
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- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Nebraska Medicine-Bellevue
Bellevue, Nebraska, 68123
CHI Health Saint Francis
Grand Island, Nebraska, 68803
Nebraska Medicine-Village Pointe Cancer Center
Omaha, Nebraska, 68118
University of Nebraska Medical Center
Omaha, Nebraska, 68198
About this study
Official title: A Phase II Study of Neoadjuvant Chemotherapy With and Without Trastuzumab in Patients With Breast Cancer
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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 for 5 years.
- Conditions
- Estrogen Receptor Negative, Estrogen Receptor Positive, HER2/Neu Negative, HER2/Neu Positive, Invasive Breast Carcinoma, Progesterone Receptor Negative
- Being tested
- Cyclophosphamide, Doxorubicin Hydrochloride, Laboratory Biomarker Analysis, Paclitaxel, Radiation Therapy
- Medical subject headings
- Breast Neoplasms, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida
Given IV
Also called 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
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
PaclitaxelDrug
Also called Anzatax, Asotax, Bristaxol, Praxel
Given IV
Radiation TherapyRadiation
Also called Cancer Radiotherapy, Irradiate, Irradiated, Irradiation
Undergo RT
Therapeutic Conventional SurgeryProcedure or surgery
Undergo mastectomy or breast conserving surgery
TrastuzumabBiological
Also called ABP 980, Anti-c-ERB-2, Anti-c-erbB2 Monoclonal Antibody, Anti-ERB-2
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (chemotherapy, surgery, post-operative therapy) | Experimental | See Detailed Description Receives: Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Radiation: Radiation Therapy; Procedure: Therapeutic Conventional Surgery; Biological: Trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Incidence of Toxicities, Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Number of participants in each subset (Her2 positive and Her2 negative) who experience at least one adverse event [overall incidence of toxicities, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0].
Measured: Up to 30 days after completion of study treatment, maximum of 114 days
Overall Severity of Toxicities, Graded According to the NCI CTCAE Version 4.0
Results reported as total events per grade for human epidermal growth factor receptor 2 (HER2)negative and HER2 positive (Overall severity of toxicities, graded according to the NCI CTCAE version 4.0).
Measured: Up to 30 days after completion of study treatment, maximum of 114 days
Number of Participants in the Subgroups Who Had a Pathologic Complete Response (pCR)
The number of participants in the subgroups who had a pathologic complete response (pCR) determined from the surgical specimen and 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.
Measured: Up to 12 weeks (after the first 6 courses of treatment), maximum of 168 days
Secondary outcomes (4)
Clinical Complete Response
The absence of all detectable cancer after treatment is complete
Measured: up to 2 years
Failure- Free Survival (FFS)
The analysis will be based on Kaplan- Meier estimates. FFS will be summarized overall and for human epidermal growth factor receptor 2 (HER2) + and HER- subsets
Measured: 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
Identification of Gene Expression Profile Signatures That Correlate With Clinical Response as Measured by pCR
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.
Measured: Up to 2 years
Overall Survival (OS)
The analysis will be based on Kaplan-Meier estimates. OS will be summarized overall and for HER+ and HER- subsets.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2012 (estimated)
- Study start7 Dec 2012
- Primary completion1 May 2022
- Study completion24 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Estrogen Receptor NegativeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 92 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Amulya C Yellala, MD, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01750073
- Sponsor's protocol ID
- 0264-12-FB
- Other IDs
- NCI-2012-01372, P30CA036727
- Status last verified
- Nov 2025
- First submitted
- 12 Dec 2012
- Last updated
- 26 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No