search
Back to results

Cyclophosphamide, Paclitaxel, and Trastuzumab in Treating Stage I-II HER2/Neu Positive Breast Cancer After Surgery

Primary Purpose

HER2 Positive Breast Carcinoma, Stage I Breast Cancer AJCC v7, Stage IA Breast Cancer AJCC v7

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cyclophosphamide
Laboratory Biomarker Analysis
Paclitaxel
Trastuzumab
Sponsored by
University of Nebraska
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HER2 Positive Breast Carcinoma

Eligibility Criteria

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

Inclusion Criteria:

  • Histologically confirmed newly diagnosed stage I-II HER2/neu positive breast cancer
  • 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)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Within 30 days prior to enrollment: Absolute neutrophil count greater than or equal to 1,500/mcl
  • Within 30 days prior to enrollment: Platelet count equal to or greater than 150,000/mcl
  • Within 30 days prior to enrollment: Hemoglobin > 11 gm/dl
  • Within 30 days prior to enrollment: Alkaline phosphatase equal or less than 1.5 times the upper limit of normal (ULN)
  • Within 30 days prior to enrollment: Total bilirubin equal to or less than 1.5 times the ULN
  • Within 30 days prior to enrollment: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) no greater than 1.5 times the ULN
  • Within 30 days prior to enrollment: Creatinine less than 1.5 times the ULN
  • Able to give informed consent
  • All included subjects must have normal cardiac function as defined by an ejection fraction of > 50% by echocardiogram
  • Able to return for treatment and follow-up on the specified days

Exclusion Criteria:

  • Prior malignancy; except for adequately treated basal cell or squamous cell skin cancer or noninvasive carcinomas
  • Subjects with pre-existing grade II peripheral neuropathy
  • History of previous chemotherapy
  • Stage IV or metastatic breast cancer
  • Pregnant or nursing women
  • Inability to cooperate with treatment protocol
  • No active serious infections or other conditions precluding chemotherapy
  • Any comorbidity or condition which, in the opinion of the investigator, may interfere with the assessments and procedures of this protocol e.g. unstable angina, myocardial infarction within 6 months, severe infection, etc.
  • Known hypersensitivity to any component of required drugs in the study
  • Known positive for human immunodeficiency virus (HIV) or infectious hepatitis, type A, B or C or active hepatitis
  • 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 electrocardiographic (ECG) abnormality at screening has to be documented by the investigator as not medically relevant

Sites / Locations

  • Faith Regional Health Services Carson Cancer Center
  • Nebraska Medicine-Village Pointe
  • University of Nebraska Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (cyclophosphamide, paclitaxel, trastuzumab)

Arm Description

SYSTEMIC THERAPY: Patients receive cyclophosphamide IV over 1 hour, paclitaxel IV over 3 hours, and trastuzumab IV over 30-90 minutes on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE TRASTUZUMAB THERAPY: Beginning in course 6, patients receive trastuzumab IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Patients may undergo radiation therapy at the discretion of the radiation oncologist and medical oncologist and patients with estrogen/progesterone receptor positive tumors receive hormonal therapy as determined by the medical oncologist per standard NCCN guidelines.

Outcomes

Primary Outcome Measures

Incidence of neutropenia, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.03
The incidence rates of neutropenia and adverse events will be summarized using frequencies, percentages and 90% confidence intervals. Adverse events will be described by cycle. The frequency of toxicity, categorized by toxicity grades, will be summarized.
Incidence of paclitaxel-related neuropathy, graded according to the NCI CTCAE v4.03
The incidence rates of paclitaxel-related neuropathy and adverse events will be summarized using frequencies, percentages and 90% confidence intervals. Adverse events will be described by cycle. The frequency of toxicity, categorized by toxicity grades, will be summarized.
Incidence of grade 3/4 cardiotoxicity, graded according to the NCI CTCAE v4.03
The incidence rates of grade 3/4 cardiotoxicity and adverse events will be summarized using frequencies, percentages and 90% confidence intervals. Adverse events will be described by cycle. The frequency of toxicity, categorized by toxicity grades, will be summarized.
Incidence of grade 3/4 nausea/vomiting, graded according to the NCI CTCAE v4.03
The incidence rates of grade 3/4 nausea/vomiting and adverse events will be summarized using frequencies, percentages and 90% confidence intervals. Adverse events will be described by cycle. The frequency of toxicity, categorized by toxicity grades, will be summarized.
Recurrence free survival (RFS)
RFS and survival curves will be plotted following the method of Kaplan and Meier using the full analysis set.
Incidence of inability to complete treatment, defined as a patient that requires a lower dose of therapy (defined as dose lowered by 50%), or a postponement of scheduled treatment of longer than 28 days, or discontinuation of treatment for any reason
Inability to complete treatment will be described using frequencies and proportions and 90% confidence intervals.

Secondary Outcome Measures

Full Information

First Posted
January 11, 2016
Last Updated
October 9, 2023
Sponsor
University of Nebraska
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT02654119
Brief Title
Cyclophosphamide, Paclitaxel, and Trastuzumab in Treating Stage I-II HER2/Neu Positive Breast Cancer After Surgery
Official Title
A Phase II Study of Adjuvant Therapy Using a Regimen of Cyclophosphamide, Paclitaxel With Trastuzumab in Stage I-II HER2/Neu Positive Breast Cancer Patients
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 11, 2015 (Actual)
Primary Completion Date
November 20, 2025 (Anticipated)
Study Completion Date
November 20, 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

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II trial studies the side effects and how well cyclophosphamide, paclitaxel, and trastuzumab work when given after surgery in treating patients with stage I-II human epidermal growth factor receptor (HER2/neu) positive breast cancer (confined to the breast or the breast and lymph nodes under the arm). Drugs used in chemotherapy, such as cyclophosphamide and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as trastuzumab, may interfere with the ability of tumor cells to grow and spread. Giving cyclophosphamide, paclitaxel, and trastuzumab after surgery may help prevent the cancer from coming back.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the toxicities and ability to complete the planned treatment of a dose-dense regimen of cyclophosphamide and paclitaxel with trastuzumab in subjects with newly diagnosed stage I-II HER2/neu positive breast cancer. II. To estimate recurrence free survival of a dose-dense regimen of cyclophosphamide and paclitaxel with trastuzumab in subjects with newly diagnosed stage I-II HER2/neu positive breast cancer. OUTLINE: SYSTEMIC THERAPY: Patients receive cyclophosphamide intravenously (IV) over 1 hour, paclitaxel IV over 3 hours, and trastuzumab IV over 30-90 minutes on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE TRASTUZUMAB THERAPY: Beginning in course 6, patients receive trastuzumab IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Patients may undergo radiation therapy at the discretion of the radiation oncologist and medical oncologist and patients with estrogen/progesterone receptor positive tumors receive hormonal therapy as determined by the medical oncologist per standard National Comprehensive Care Network (NCCN) guidelines. After completion of study treatment, patients are followed up every 3 months for 2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HER2 Positive Breast Carcinoma, Stage I Breast Cancer AJCC v7, Stage IA Breast Cancer AJCC v7, Stage IB Breast Cancer AJCC v7, Stage II Breast Cancer AJCC v6 and v7, Stage IIA Breast Cancer AJCC v6 and v7, Stage IIB Breast Cancer AJCC v6 and v7

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (cyclophosphamide, paclitaxel, trastuzumab)
Arm Type
Experimental
Arm Description
SYSTEMIC THERAPY: Patients receive cyclophosphamide IV over 1 hour, paclitaxel IV over 3 hours, and trastuzumab IV over 30-90 minutes on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE TRASTUZUMAB THERAPY: Beginning in course 6, patients receive trastuzumab IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Patients may undergo radiation therapy at the discretion of the radiation oncologist and medical oncologist and patients with estrogen/progesterone receptor positive tumors receive hormonal therapy as determined by the medical oncologist per standard NCCN guidelines.
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
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
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, Ogivri, PF-05280014, rhuMAb HER2, RO0452317, Trastuzumab Biosimilar ABP 980, Trastuzumab Biosimilar PF-05280014, Trastuzumab-dkst
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Incidence of neutropenia, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.03
Description
The incidence rates of neutropenia and adverse events will be summarized using frequencies, percentages and 90% confidence intervals. Adverse events will be described by cycle. The frequency of toxicity, categorized by toxicity grades, will be summarized.
Time Frame
Up to 3 months after final chemotherapy treatment (including trastuzumab)
Title
Incidence of paclitaxel-related neuropathy, graded according to the NCI CTCAE v4.03
Description
The incidence rates of paclitaxel-related neuropathy and adverse events will be summarized using frequencies, percentages and 90% confidence intervals. Adverse events will be described by cycle. The frequency of toxicity, categorized by toxicity grades, will be summarized.
Time Frame
Up to 3 months after final chemotherapy treatment (including trastuzumab)
Title
Incidence of grade 3/4 cardiotoxicity, graded according to the NCI CTCAE v4.03
Description
The incidence rates of grade 3/4 cardiotoxicity and adverse events will be summarized using frequencies, percentages and 90% confidence intervals. Adverse events will be described by cycle. The frequency of toxicity, categorized by toxicity grades, will be summarized.
Time Frame
Up to 3 months after final chemotherapy treatment (including trastuzumab)
Title
Incidence of grade 3/4 nausea/vomiting, graded according to the NCI CTCAE v4.03
Description
The incidence rates of grade 3/4 nausea/vomiting and adverse events will be summarized using frequencies, percentages and 90% confidence intervals. Adverse events will be described by cycle. The frequency of toxicity, categorized by toxicity grades, will be summarized.
Time Frame
Up to 3 months after final chemotherapy treatment (including trastuzumab)
Title
Recurrence free survival (RFS)
Description
RFS and survival curves will be plotted following the method of Kaplan and Meier using the full analysis set.
Time Frame
First date of therapy until the first notation of clinical progression, relapse or death from any cause, assessed at 2 years
Title
Incidence of inability to complete treatment, defined as a patient that requires a lower dose of therapy (defined as dose lowered by 50%), or a postponement of scheduled treatment of longer than 28 days, or discontinuation of treatment for any reason
Description
Inability to complete treatment will be described using frequencies and proportions and 90% confidence intervals.
Time Frame
Up to 2 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed newly diagnosed stage I-II HER2/neu positive breast cancer 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) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Within 30 days prior to enrollment: Absolute neutrophil count greater than or equal to 1,500/mcl Within 30 days prior to enrollment: Platelet count equal to or greater than 150,000/mcl Within 30 days prior to enrollment: Hemoglobin > 11 gm/dl Within 30 days prior to enrollment: Alkaline phosphatase equal or less than 1.5 times the upper limit of normal (ULN) Within 30 days prior to enrollment: Total bilirubin equal to or less than 1.5 times the ULN Within 30 days prior to enrollment: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) no greater than 1.5 times the ULN Within 30 days prior to enrollment: Creatinine less than 1.5 times the ULN Able to give informed consent All included subjects must have normal cardiac function as defined by an ejection fraction of > 50% by echocardiogram Able to return for treatment and follow-up on the specified days Exclusion Criteria: Prior malignancy; except for adequately treated basal cell or squamous cell skin cancer or noninvasive carcinomas Subjects with pre-existing grade II peripheral neuropathy History of previous chemotherapy Stage IV or metastatic breast cancer Pregnant or nursing women Inability to cooperate with treatment protocol No active serious infections or other conditions precluding chemotherapy Any comorbidity or condition which, in the opinion of the investigator, may interfere with the assessments and procedures of this protocol e.g. unstable angina, myocardial infarction within 6 months, severe infection, etc. Known hypersensitivity to any component of required drugs in the study Known positive for human immunodeficiency virus (HIV) or infectious hepatitis, type A, B or C or active hepatitis 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 electrocardiographic (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, MD
Organizational Affiliation
University of Nebraska
Official's Role
Principal Investigator
Facility Information:
Facility Name
Faith Regional Health Services Carson Cancer Center
City
Norfolk
State/Province
Nebraska
ZIP/Postal Code
68701
Country
United States
Facility Name
Nebraska Medicine-Village Pointe
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

Cyclophosphamide, Paclitaxel, and Trastuzumab in Treating Stage I-II HER2/Neu Positive Breast Cancer After Surgery

We'll reach out to this number within 24 hrs