A Phase 2 interventional study of Cyclophosphamide and Doxorubicin Hydrochloride in Estrogen Receptor Negative, Estrogen Receptor Positive and HER2/Neu Negative, sponsored by University of Nebraska. Completed at 4 sites in United States. Open to female participants aged 19 Years and older. Per ClinicalTrials.gov, last updated 2026-06-26.
Sponsored by University of Nebraska · Phase 2, Interventional, and Treatment
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.
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 for 5 years.
12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.
This study's enrollment of 92 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →University of Nebraska is the lead sponsor of 473 studies on the registry; 66 are open to participants now.
Of its 75 completed or terminated interventional studies of FDA-regulated products, 46 (61%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
See Detailed Description
Drug: Cyclophosphamide · Drug: Doxorubicin Hydrochloride · Other: Laboratory Biomarker Analysis · Drug: Paclitaxel · Radiation: Radiation Therapy · Procedure: Therapeutic Conventional Surgery · Biological: Trastuzumab
Given IV
Also known as: (-)-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
Given IV
Also known as: 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
Correlative studies
Given IV
Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat
Undergo RT
Also known as: Cancer Radiotherapy, Irradiate, Irradiated, Irradiation, RADIATION, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation
Undergo mastectomy or breast conserving surgery
Given IV
Also known as: 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
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 \[overall incidence of toxicities, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0\].
Time frame: 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).
Time frame: 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.
Time frame: Up to 12 weeks (after the first 6 courses of treatment), maximum of 168 days
Clinical Complete Response
The absence of all detectable cancer after treatment is complete
Time frame: 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
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
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.
Time frame: 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.
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
| Milestone | Treatment (Chemotherapy, Surgery, Post-operative Therapy) |
|---|---|
| Started | 92 |
| Her2-positive | 19 |
| Her2-negative | 73 |
| Completed | 87 |
| Not completed | 5 |
Number of participants in each subset (Her2 positive and Her2 negative) who experience at least one adverse event \[overall incidence of toxicities, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0\].
| Participants | Her-2 Negative | Her-2 Positive |
|---|---|---|
| Overall Incidence of Toxicities, Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | 73 | 19 |
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).
| Events | Her-2 Negative | Her-2 Positive |
|---|---|---|
| SAE grade 1 | 1 | 9 |
| SAE grade 2 | 10 | 4 |
| SAE grade 3 | 22 | 8 |
| SAE grade 4 | 2 | 2 |
| SAE grade 5 | 1 | 1 |
| Non-SAE grade 1 | 1286 | 302 |
| Non-SAE grade 2 | 390 | 143 |
| Non-SAE grade 3 | 93 | 23 |
| Non-SAE grade 4 | 11 | 4 |
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.
| participants | Her-2 Negative | Her-2 Positive |
|---|---|---|
| Number of Participants in the Subgroups Who Had a Pathologic Complete Response (pCR) | 13 | 2 |
The absence of all detectable cancer after treatment is complete
Results for this outcome have not been posted.
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
Results for this outcome have not been posted.
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.
Results for this outcome have not been posted.
The analysis will be based on Kaplan-Meier estimates. OS will be summarized overall and for HER+ and HER- subsets.
Results for this outcome have not been posted.
Collected over 30 days after last administration of study medication, maximum of 114 days. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treatment (Chemotherapy, Surgery, Post-operative Therapy) | 2/92 (2.2%) | 16/92 (17.4%) | 92/92 (100%) |
| Event | Treatment (Chemotherapy, Surgery, Post-operative Therapy) |
|---|---|
| Febrile NeutropeniaBlood and lymphatic system disorders | 5/92 |
| AnemiaBlood and lymphatic system disorders | 3/92 |
| Infections and InfestationsInfections and infestations | 3/92 |
| SepsisInfections and infestations | 3/92 |
| DehydrationMetabolism and nutrition disorders | 2/92 |
| FeverGeneral disorders | 2/92 |
| HyperglycemiaMetabolism and nutrition disorders | 2/92 |
| Neutrophil count decreasedInvestigations | 2/92 |
| non-cardiac chest painGeneral disorders | 2/92 |
| Peripheral sensory neuropathyNervous system disorders | 2/92 |
| Event | Treatment (Chemotherapy, Surgery, Post-operative Therapy) |
|---|---|
| Peripheral sensory neuropathyNervous system disorders | 81/92 |
| HyperglycemiaMetabolism and nutrition disorders | 66/92 |
| FatigueGeneral disorders | 55/92 |
| Alkaline phosphatase increasedInvestigations | 54/92 |
| AnemiaBlood and lymphatic system disorders | 49/92 |
| NauseaGastrointestinal disorders | 48/92 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 41/92 |
| White blood cell decreasedInvestigations | 38/92 |
| MyalgiaMusculoskeletal and connective tissue disorders | 36/92 |
| ConstipationGastrointestinal disorders | 35/92 |
| Age, Continuous(Years) | Treatment (Chemotherapy, Surgery, Post-operative Therapy) |
|---|---|
| Mean | 57.65 ± 10.19 |
| Sex: Female, Male(Participants) | Treatment (Chemotherapy, Surgery, Post-operative Therapy) |
|---|---|
| Female | 92 |
| Male | 0 |
| Ethnicity (NIH/OMB)(Participants) | Treatment (Chemotherapy, Surgery, Post-operative Therapy) |
|---|---|
| Hispanic or Latino | 3 |
| Not Hispanic or Latino | 89 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Treatment (Chemotherapy, Surgery, Post-operative Therapy) |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 1 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 11 |
| White | 80 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Stage of Cancer(Participants) | Treatment (Chemotherapy, Surgery, Post-operative Therapy) |
|---|---|
| Stage I | 22 |
| Stage II | 65 |
| Stage IIIA | 5 |
| Her-2 NEU Status (human epidermal growth factor receptor)(Participants) | Treatment (Chemotherapy, Surgery, Post-operative Therapy) |
|---|---|
| Negative | 73 |
| Positive | 19 |
| ER Status(Participants) | Treatment (Chemotherapy, Surgery, Post-operative Therapy) |
|---|---|
| Negative | 35 |
| Positive | 57 |
| PR Status (progesterone receptors)(Participants) | Treatment (Chemotherapy, Surgery, Post-operative Therapy) |
|---|---|
| Negative | 49 |
| Positive | 43 |
2 further baseline measures are reported on the registry.
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