HER2-Positive Early Stage Breast Cancer
Conditions
Keywords
Paclitaxel, Trastuzumab, Lapatinib, HER2, 13-002
Brief summary
The purpose of this study is to study a new treatment for HER2-positive breast cancer.
Interventions
DRUGPaclitaxel
DRUGTrastuzumab
The q 3 week trastuzumab may be started at the last dose of paclitaxel infusion or from 1-3 weeks after the last dose of paclitaxel. Trastuzumab may also be administered at a dose of 6mg/kg during the last dose of paclitaxel in the THL phase.
DRUGLapatinib
DRUGPegfilgrastim
Pegfilgrastim SQ is given on day # 2 of each paclitaxel cycle and may be dropped at the last paclitaxel infusion. Filgrastim may be used in lieu of pegfilgrastim at the physician's discretion.
Sponsors
GlaxoSmithKline
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have histologically confirmed adenocarcinoma with HER2/neu immunohistochemistry 3+ or FISH-amplified breast cancer with a ratio of ≥ 2.0 * Tumor size of ≤ 3 cm and node-negative disease. Nodes with single cells or tumor clusters \< 0.2 mm by H&E or IHC are considered node-negative. Patients with micrometastasis (nodes with tumor clusters between 0.02 and 0.2 cm) are allowed. Further axillary dissection will be determined by the patient's surgeon as per standard of care. * Patients must be ≥18 years of age. * Patients must have an ECOG performance status of 0 or 1. * Treatment should be started within 90 days of the final surgical procedure for breast cancer. * Patients may have bilateral synchronous breast tumors. Patients may have received hormonal therapy for the purpose of chemoprevention but must be willing to discontinue prior to enrollment and while participating in this trial. * If patients have peripheral neuropathy, it must be ≤ grade 1. * Patients must be willing to discontinue sex hormonal therapy e.g., birth control pills, ovarian hormonal replacement therapy, etc., prior to enrollment. Women of childbearing potential must be willing to consent to using effective contraception while on treatment and for a reasonable period thereafter. * Hematologic parameters: absolute neutrophil count (ANC) ≥1500/μL and platelet count ≥100,000/μL. * Non-hematologic parameters: total bilirubin must be ≤ 1.5 X institutional upper limit of normal (ULN), transaminases (SGOT or SGPT) ≤ 3.0 x ULN. * Negative HCG pregnancy test for premenopausal women of reproductive capacity and for women less than 12 months after the menopause. LVEF by ECHO (with strain if possible) with LVEF of ≥ 50%. If an ECHO cannot be done, a MUGA may be performed. * Patients must give written, informed consent indicating their understanding of and willingness to participate in the study.
Exclusion criteria
* Patients with stage IV breast cancer or undergoing chemotherapy, radiation therapy, immunotherapy, or biotherapy for current breast cancer. * Pregnant or breastfeeding patients. * Patients with a concurrently active second malignancy, other than adequately treated non-melanoma skin cancers or in situ cervical cancer. * Patients with unstable angina, congestive heart failure, or with a history of a myocardial infarction within 12 months. Patients with high-risk uncontrolled arrhythmias (ventricular tachycardia, high-grade AV block, supraventricular arrhythmias which are not adequately rate-controlled). Patients are excluded if they have grade 3 QT prolongation (Appendix F) (\>500 ms) or require drugs that may prolong the QT. * Subjects who have current active hepatic (including hepatitis B or C) or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones). * Patients with active, unresolved infections. * Patients with a sensitivity to E. coli derived proteins.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Are Able to Complete THL (Paclitaxel, Trastuzumab, and Lapatinib) Without a Dose Delay or Reduction, Grade 3 or Greater QTc Prolongation | 1 year | The primary objective of this trial is to determine the feasibility of this regimen in patients with node-negative HER-2/neu overexpressed /amplified breast cancer with a tumor size of \< 3 cm. The regimen is considered feasible if patients are able to complete the paclitaxel, trastuzumab, and lapatinib (THL) portion of the regimen without a dose delay or reduction or grade 3 or greater QTc prolongation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants Toxicity Evaluated While on Study Treatment | 1 year | All toxicities following chemotherapy will be graded using the National Cancer Institute - Common Toxicity Criteria version 4.0. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Paclitaxel With Trastuzumab and Lapatinib Paclitaxel (T) at 175 mg/m2 q 2 weeks x 4 with filgrastim/pegfilgrastim + trastuzumab (H) + daily oral lapatinib (L), followed by trastuzumab q 3 weeks x 15 doses + daily oral lapatinib (HL). Pegfilgrastim 6mg will be given subcutaneously (SQ) on day # 2 of each paclitaxel administration. Filgrastim may be used in lieu of pegfilgrastim at physician's discretion. Trastuzumab will be administered weekly (4 mg/kg bolus followed by 2 mg/kg weekly) starting with paclitaxel treatment cycle # 1. After 4 cycles of paclitaxel, pts will receive trastuzumab on a q 3 weeks x 15 doses (to complete about one year). The q 3 week trastuzumab may be started from 1-3 weeks after the last dose of paclitaxel. A total of 15 infusions of trastuzumab will be given q 3 weeks after the completion of paclitaxel during the HL phase. Lapatinib will be given orally at 1000 mg daily, starting with paclitaxel during the THL phase & continued for the remaining year during the HL phase for about a year.
Paclitaxel | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 9 |
| Overall Study | Hypersensitivity reaction to Paclitaxel | 2 |
Baseline characteristics
| Characteristic | Paclitaxel With Trastuzumab and Lapatinib |
|---|---|
| Age, Continuous | 49 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 16 Participants |
| Region of Enrollment United States | 20 Participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 20 / 20 |
| serious Total, serious adverse events | 4 / 20 |
Outcome results
Primary
Number of Participants Who Are Able to Complete THL (Paclitaxel, Trastuzumab, and Lapatinib) Without a Dose Delay or Reduction, Grade 3 or Greater QTc Prolongation
The primary objective of this trial is to determine the feasibility of this regimen in patients with node-negative HER-2/neu overexpressed /amplified breast cancer with a tumor size of \< 3 cm. The regimen is considered feasible if patients are able to complete the paclitaxel, trastuzumab, and lapatinib (THL) portion of the regimen without a dose delay or reduction or grade 3 or greater QTc prolongation.
Time frame: 1 year
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Paclitaxel With Trastuzumab and Lapatinib | Number of Participants Who Are Able to Complete THL (Paclitaxel, Trastuzumab, and Lapatinib) Without a Dose Delay or Reduction, Grade 3 or Greater QTc Prolongation | Did not complete treatment | 16 Participants |
| Paclitaxel With Trastuzumab and Lapatinib | Number of Participants Who Are Able to Complete THL (Paclitaxel, Trastuzumab, and Lapatinib) Without a Dose Delay or Reduction, Grade 3 or Greater QTc Prolongation | Successfully completed treatment | 4 Participants |
Secondary
Participants Toxicity Evaluated While on Study Treatment
All toxicities following chemotherapy will be graded using the National Cancer Institute - Common Toxicity Criteria version 4.0.
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Paclitaxel With Trastuzumab and Lapatinib | Participants Toxicity Evaluated While on Study Treatment | 20 Participants |