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

Primary Purpose

Estrogen Receptor Negative, Estrogen Receptor Positive, HER2/Neu Negative

Status

Active

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Cyclophosphamide

Doxorubicin Hydrochloride

Laboratory Biomarker Analysis

Paclitaxel

Radiation Therapy

Therapeutic Conventional Surgery

Trastuzumab

About this trial

This is an interventional treatment trial for Estrogen Receptor Negative

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

Nebraska Medicine-Bellevue
CHI Health Saint Francis
Nebraska Medicine-Village Pointe Cancer Center
University of Nebraska Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (chemotherapy, surgery, post-operative therapy)

Arm Description

See Detailed Description

Outcomes

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

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

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

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

Failure-free survival (FFS)

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

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)

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

Full Information

NCT ID

NCT01750073

First Posted

December 12, 2012

Last Updated

July 12, 2023

Sponsor

University of Nebraska

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01750073

Brief Title

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

Official Title

A Phase II Study of Neoadjuvant Chemotherapy With and Without Trastuzumab in Patients With Breast Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

December 2012 (undefined)

Primary Completion Date

May 2022 (Actual)

Study Completion Date

June 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Nebraska

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

99 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment (chemotherapy, surgery, post-operative therapy)

Arm Type

Experimental

Arm Description

See Detailed Description

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

(-)-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

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Doxorubicin Hydrochloride

Other Intervention Name(s)

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

Intervention Description

Given IV

Intervention Type

Other

Intervention Name(s)

Laboratory Biomarker Analysis

Intervention Description

Correlative studies

Intervention Type

Drug

Intervention Name(s)

Paclitaxel

Other Intervention Name(s)

Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Intervention Description

Given IV

Intervention Type

Radiation

Intervention Name(s)

Radiation Therapy

Other Intervention Name(s)

Cancer Radiotherapy, Irradiate, Irradiated, Irradiation, RADIATION, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Intervention Description

Undergo RT

Intervention Type

Procedure

Intervention Name(s)

Therapeutic Conventional Surgery

Intervention Description

Undergo mastectomy or breast conserving surgery

Intervention Type

Biological

Intervention Name(s)

Trastuzumab

Other Intervention Name(s)

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

Intervention Description

Given IV

Primary Outcome Measure Information:

Title

Overall incidence of toxicities, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Description

Time Frame

Up to 30 days after completion of study treatment

Title

Overall severity of toxicities, graded according to the NCI CTCAE version 4.0

Description

Time Frame

Up to 30 days after completion of study treatment

Title

Description

Time Frame

Up to 12 weeks (after the first 6 courses of treatment)

Secondary Outcome Measure Information:

Title

Clinical complete response

Time Frame

Up to 2 years

Title

Failure-free survival (FFS)

Description

The analysis will be based on Kaplan-Meier estimates. FFS will be summarized overall and for HER+ 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

Title

Identification of gene expression profile signatures that correlate with clinical response as measured by pCR

Description

Time Frame

Up to 2 years

Title

Overall survival (OAS)

Description

The analysis will be based on Kaplan-Meier estimates. OAS 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

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

19 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Amulya Yellala

Organizational Affiliation

University of Nebraska

Official's Role

Principal Investigator

Facility Information:

Facility Name

Nebraska Medicine-Bellevue

City

Bellevue

State/Province

Nebraska

ZIP/Postal Code

68123

Country

United States

Facility Name

CHI Health Saint Francis

City

Grand Island

State/Province

Nebraska

ZIP/Postal Code

68803

Country

United States

Facility Name

Nebraska Medicine-Village Pointe Cancer Center

City

Omaha

State/Province

Nebraska

ZIP/Postal Code

68118

Country

United States

Facility Name

University of Nebraska Medical Center

City

Omaha

State/Province

Nebraska

ZIP/Postal Code

68198

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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