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
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- University of Nebraska
- Enrollment
- 20
- Locations
- 3
- Primary Endpoint
- Number Participants With Neutropenia, Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version (v)4.03
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 20 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
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
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
Arms & Interventions
Treatment (cyclophosphamide, paclitaxel, trastuzumab)
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: Cyclophosphamide (Drug)
Treatment (cyclophosphamide, paclitaxel, trastuzumab)
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: Laboratory Biomarker Analysis (Other)
Treatment (cyclophosphamide, paclitaxel, trastuzumab)
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: Paclitaxel (Drug)
Treatment (cyclophosphamide, paclitaxel, trastuzumab)
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: Trastuzumab (Biological)
Outcomes
Primary Outcomes
Number Participants With Neutropenia, Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version (v)4.03
Time Frame: From initiation of study treatment through completion of therapy and up to 3 months after the final dose of study treatment (including trastuzumab).
Number of participants who experienced Neutropenia.
Number of Participants With Paclitaxel-related Neuropathy, Graded According to the NCI CTCAE v4.03
Time Frame: From initiation of study treatment through completion of therapy and up to 3 months after the final dose of study treatment (including trastuzumab).
Number of Participants experienced paclitaxel-related neuropathy and adverse events
Number of Participants With Cardiotoxicity Grade 3/4 Cardiotoxicity, Graded According to the NCI CTCAE v4.03
Time Frame: From initiation of study treatment through completion of therapy and up to 3 months after the final dose of study treatment (including trastuzumab).
Participants experienced grade 3/4 cardiotoxicity with standard treatment
Number of Participants With Grade 3/4 Nausea/Vomiting, Graded According to the NCI CTCAE v4.03
Time Frame: From initiation of study treatment through completion of therapy and up to 3 months after the final dose of study treatment (including trastuzumab).
Participants that experienced grade 3/4 nausea/vomiting with this regimen when compared to standard regimens.
Number of Participants With Recurrence Free Survival (RFS)
Time Frame: First date of therapy until the first notation of clinical progression, relapse or death from any cause, assessed at 2 years
RFS and survival curves will be plotted following the method of Kaplan and Meier using the full analysis set.
Number of Participants With 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 for Any Reason
Time Frame: Up to 2 years
Number of participants with 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. will be described using frequencies and proportions and 90% confidence intervals.
Secondary Outcomes
No secondary outcomes reported