ErbB2-Positive Stage I-III Breast Cancer Clinical Trial
Official title:
Phase II Open-Label Study of Preoperative Weekly Paclitaxel and Carboplatin With Lapatinib (Tykerb®) in Patients With ErbB2-Positive Stage I-III Breast Cancer
The purpose of this study is to evaluate the efficacy and safety of weekly paclitaxel and
carboplatin, in combination with lapatinib, in the neoadjuvant treatment of non-metastatic
erbB2-positive breast cancer.
Secondary objectives include:
- To determine the safety and tolerability of weekly paclitaxel and carboplatin, combined
with lapatinib, in an Asian population
- To determine breast conservation rates following neoadjuvant paclitaxel/ carboplatin/
lapatinib
- To determine clinical response rates and relapse-free survival of patients treated with
neoadjuvant paclitaxel/ carboplatin/ lapatinib
- To identify predictive tumour biomarkers for pathologic complete response
The investigators hypothesize that pathologic complete response rates will be improved from
15% to 35% with the neoadjuvant regimen of carboplatin/ paclitaxel/ lapatinib compared to
standard chemotherapy alone in HER2 positive early stage breast cancers.
| Status | Active, not recruiting |
| Enrollment | 34 |
| Est. completion date | December 2015 |
| Est. primary completion date | December 2014 |
| Accepts healthy volunteers | No |
| Gender | Female |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - • Female, Age = 18 years - Histologic or cytologic diagnosis of breast carcinoma - T1-4 breast cancer with measurable primary breast tumor, defined as palpable tumor with the largest diameter measuring 2.0cm or greater by calipers - Tumor is HER2 positive either by IHC (3+) or FISH amplification (amplification ratio >2.2) - Patients must not have received prior chemotherapy or hormonal therapy for the treatment of breast cancer - Karnofsky performance status of 70 or higher - Estimated life expectancy of at least 12 weeks - Adequate organ function including the following: Bone marrow: - Absolute neutrophil (segmented and bands) count (ANC) >= 1.5 x 109/L - Platelets >= 100 x 109/L Hepatic: - Bilirubin <= 1.5 x upper limit of normal (ULN), - ALT or AST <= 2.5x ULN Renal: o Calculated creatinine clearance >30ml/minute - Left ventricular ejection fraction >=50% measured by 2D echo or MUGA - Signed informed consent from patient or legal representative - Patient with reproductive potential must use an approved contraceptive method if appropriate (e.g. intrauterine device, birth control pills, or barrier device) during and for three months after the study. Females with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment Exclusion Criteria: - • Prior treatment for locally advanced or metastatic breast cancer - Treatment within the last 30 days with any investigational drug - Concurrent administration of any other tumor therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy - Major surgery within 28 days of study drug administration - Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy - Breast feeding - Serious cardiac illness or medical conditions including but not confined to: - History of documented congestive cardiac failure or systolic dysfunction (LVEF <50%) - High-risk uncontrolled arrhythmias (ventricular tachycardia, high-grade AV block, supraventricular arrhythmias which are not adequately rate-controlled) - History of significant ischaemic heart disease - Clinically significant valvular heart disease - Poorly controlled hypertension (e.g. systolic BP > 180mmHg or diastolic >100mmHg) - Poorly controlled diabetes mellitus. - Second primary malignancy that is clinically detectable at the time of consideration for study enrollment. - History of significant neurological or mental disorder, including seizures or dementia. - Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones or stable chronic liver disease per investigator assessment) - Concomitant use of CYP3A4 inhibitors |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Singapore | National University Hospital | Singapore |
| Lead Sponsor | Collaborator |
|---|---|
| National University Hospital, Singapore | National Cancer Centre, Singapore |
Singapore,
Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, Wickerham DL, Begovic M, DeCillis A, Robidoux A, Margolese RG, Cruz AB Jr, Hoehn JL, Lees AW, Dimitrov NV, Bear HD. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998 Aug;16(8):2672-85. — View Citation
Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43. Erratum in: N Engl J Med. 2007 Apr 5;356(14):1487. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Rate of pathologic complete response | 12 weeks | Yes | |
| Secondary | Treatment related toxicities | 12 weeks | Yes | |
| Secondary | Breast conservation rates | 16 weeks | No | |
| Secondary | Clinical response rates | 1 year | No | |
| Secondary | Relapse free survival (RFS) | 2 years | No | |
| Secondary | Identification of tumor biomarkers that predict pathologic complete response | 16 weeks | No |