Phase II Trial of Adjuvant TC (Docetaxel/Cyclophosphamide) Plus Trastuzumab in HER2-Positive Early Stage Breast Cancer Patients
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- US Oncology Research
- Enrollment
- 493
- Locations
- 64
- Primary Endpoint
- Disease-free Survival (DFS) Rate at 2 Years in TOP2A-amplified and in TOP2A-nonamplified HER2+ ESBC Patients Treated With TC+H.
Overview
Brief Summary
The purpose of this research study is to find out what effects (good and bad) docetaxel/cyclophosphamide (brand names: Taxotere and Cytoxan, or TC) plus trastuzumab (brand name: Herceptin, or H) has HER2+ breast cancer.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •A woman will be eligible for inclusion in this study if she meets all of the following criteria:
- •Has HER2+ (IHC staining of 3+ \[uniform, intense membrane staining of \>30% of invasive tumor cells\], or a FISH result of .6 HER2 gene copies per nucleus or a FISH ratio \[HER2 gene signals to chromosome 17 signals\] of \>2.2; patients with equivocal FISH ratio results 1.8-2.2 are also eligible if 3+ IHC) (Appendix IX); Stage I, IIA, IIB, or IIIA T1-3N1-3M0 disease. At the discretion of the Treating Physician, patients with 4+ nodes with other factors such as patient choice, older age, preexisting cardiac disease with normal MUGA or ECHO may be enrolled into a separate subgroup.
- •Has operable, histologically confirmed, invasive carcinoma of the breast.
- •Has known ER and PR status
- •Has adequate tumor specimen available for FISH analysis of TOP2A status (See Appendix VII)
- •Has had no prior chemotherapy unless it was given \>5 years ago for breast cancer or other cancer
- •Has an ECOG Performance Status (PS) 0-1
- •Age \>18 to \<70 years old.
- •Has laboratory values of: See protocol for specific details
- •Has aspartate aminotransferase (AST) or alanine aminotransferase (ALT) and alkaline phosphatase (ALP) within the ranges shown below. In determining eligibility the more abnormal of the 2 values (AST or ALT) should be used. See protocol for specific details
Exclusion Criteria
- •A woman will be excluded from this study if she meets any of the following criteria:
- •Has any evidence of disease following complete surgical resection of the primary tumor and metastatic workup
- •Has Stage IIIB breast cancer (T4 disease; ie, patients with fixed tumors, peau d'orange skin changes, skin ulcerations, or inflammatory changes).
- •Has Stage IV breast cancer (M1 disease on TNM staging system)
- •Had prior chemotherapy for breast cancer or other cancer within the last 5 years (no neoadjuvant chemotherapy in this study is permitted)
- •Has a history of severe hypersensitivity reaction to drugs formulated with polysorbate 80
- •Has had a myocardial infarction (MI) within 6 months of trial enrollment, or has New York Heart Association (NYHA) Class II or greater heart failure (see Appendix III), uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic changes
- •Has abnormal baseline MUGA (or ECHO) (\<50%, or less than institutional LLN)
- •Is receiving concurrent immunotherapy, hormonal therapy, or radiation therapy. Adjuvant hormonal therapy, if needed, may be given during radiation therapy and during treatment with trastuzumab after completion of chemotherapy.
- •Is receiving concurrent investigational therapy or has received such therapy within the past 30 calendar days
Arms & Interventions
TC+H
On Day 1 of each 21-day cycle for a total of 4 cycles, patients will receive, in this order: docetaxel (Taxotere) 75 mg/m2 IV (over 1 hour), plus cyclophosphamide (Cytoxan) 600 mg/m2 IV (over 15-30 minutes), plus weekly trastuzumab (Herceptin) 4 mg/kg IV (loading dose, over 90 minutes Day 1, Cycle 1 only) and 2 mg/kg IV (over 30-60 minutes on Days 1, 8, and 15) thereafter.
Intervention: Taxotere (Drug)
TC+H
On Day 1 of each 21-day cycle for a total of 4 cycles, patients will receive, in this order: docetaxel (Taxotere) 75 mg/m2 IV (over 1 hour), plus cyclophosphamide (Cytoxan) 600 mg/m2 IV (over 15-30 minutes), plus weekly trastuzumab (Herceptin) 4 mg/kg IV (loading dose, over 90 minutes Day 1, Cycle 1 only) and 2 mg/kg IV (over 30-60 minutes on Days 1, 8, and 15) thereafter.
Intervention: Cytoxan (Drug)
TC+H
On Day 1 of each 21-day cycle for a total of 4 cycles, patients will receive, in this order: docetaxel (Taxotere) 75 mg/m2 IV (over 1 hour), plus cyclophosphamide (Cytoxan) 600 mg/m2 IV (over 15-30 minutes), plus weekly trastuzumab (Herceptin) 4 mg/kg IV (loading dose, over 90 minutes Day 1, Cycle 1 only) and 2 mg/kg IV (over 30-60 minutes on Days 1, 8, and 15) thereafter.
Intervention: Herceptin (Drug)
Outcomes
Primary Outcomes
Disease-free Survival (DFS) Rate at 2 Years in TOP2A-amplified and in TOP2A-nonamplified HER2+ ESBC Patients Treated With TC+H.
Time Frame: 2 years
DFS was measured from the date of registration to either the date the patient was first recorded as having disease recurrence, or the date of death due to any causes before recurrence. If a patient had not recurred or died, DFS was censored at the date of last follow-up.
Secondary Outcomes
- Overall Survival (OS) Rate at 2 Years in TOP2A-amplified and in TOP2A-nonamplified HER2+ ESBC Patients Treated With TC+H.(2 years)
- DFS by cMyc Expression in This Population of HER2+ ESBC Patients Treated With TC+H.(2 years)
- OS by cMyc Expression in This Population of HER2+ ESBC Patients Treated With TC+H.(2 years)