Lapatinib Pre-surgical Phase II Study in Patients with Primary Breast Cancer

ISRCTN	ISRCTN71165034
DOI	https://doi.org/10.1186/ISRCTN71165034
EudraCT/CTIS number	2006-001055-36
Secondary identifying numbers	LAP106974

Submission date: 08/05/2006
Registration date: 16/06/2006
Last edited: 26/10/2018

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://www.cancerhelp.org.uk/trials/a-trial-looking-at-lapatinib-before-surgery-for-breast-cancer

Contact information

Prof Raoul Charles Coombes
Scientific

8th Floor Cycotron Building
Hammersmith Hospital
Du Cane Road
London
W12 0NN
United Kingdom

Study information

Study design	Open-label phase II sequential trial
Primary study design	Interventional
Secondary study design	Non randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	Lapatinib Pre-surgical Phase II Study in Patients with Primary Breast Cancer
Study acronym	PSL
Study objectives	Response to treatment with lapatinib before surgery will depend on oestrogen receptor (ER) phenotype.
Ethics approval(s)	MREC for Wales, 01/08/2006, ref: 06/MRE09/30
Health condition(s) or problem(s) studied	Breast cancer
Intervention	Women will be allocated to two groups (according to whether oestrogen positive or negative) and will then receive lapatinib 1500 mg daily for 4 - 6 weeks until definitive surgery.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	Lapatinib
Primary outcome measure	Response evaluation criteria in solid tumours (RECIST) by ultrasound measurement in the two treatment groups (ER+/ER-).
Secondary outcome measures	1. Change in the following biomarkers: Ki67 antibody, phosphorylated epidermal growth factor receptor (p-EGFR), phosphorylated c-erbB2 (P-c-erbB2), phosphorylated estrogen receptor (P-ER), insulin-like growth factor receptor 1 (IGFR-1), P13 kinase pathway, presence of P13 kinase mutations, expression of forkhead proteins, expression of protein kinase B (AKT), phosphorylated AKT (P-AKT), tumor suppressor Pten, cell cycle-related proteins, cyclins, cyclin-dependent kinase (CDK), apoptotic-related proteins such as caspase 3 and Bim 2. Adverse events 3. Response rates in each of the groups defined by immunostaining for EGFR as judged by the following antibody makers: 3.1. DAKO 3.2. Zymed 3.3. Biogenix 3.4. Novocastra 4. Serum markers 5. Change in c-erbB2 extracellular domain (ECD) 6. Change in EGFR ECD
Overall study start date	01/09/2006
Completion date	31/08/2008

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Female
Target number of participants	150
Key inclusion criteria	1. Patients must have histologically or cytologically confirmed breast cancer 2. Patient can be ER positive or ER negative, and must be epidermal growth factor receptor (EGFR)-positive as defined by positive immuno-staining with cell signalling antibody #2232 3. Patients must have measurable breast cancer, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than or equal to 20 mm with the conventional techniques or as greater than or equal to 10 mm with ultrasound 4. No prior systemic therapy for breast cancer is permissible 5. Aged greater than or equal to 18 years. No dosing or adverse event data are currently available on the use of lapatinib in patients less than 18 years of age; children are therefore excluded from the study 6. Life expectancy of greater than 12 weeks 7. Eastern Cooperative Oncology Group (ECOG) performance status 2 (Karnofsky greater than or equal to 60%) 8. Patients must have normal organ and marrow function as defined by: 8.1. Leukocytes greater than or equal to 3,000/µl 8.2. Absolute neutrophil count greater than or equal to 1,500/µl 8.3. Platelets greater than or equal to 100,000/µl 8.4. Total bilirubin within normal institutional limits 8.5. Serum glutamic-oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) or serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) less than or equal to 2.5 times institutional upper limit of normal 8.6. Creatinine within normal institutional limits or creatinine clearance greater than or equal to 60 ml/min/1.73 m^2 for patients with creatinine levels above institutional normal limit 9. Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram. Note that baseline and on treatment scans should be performed at the same institution. 10. Eligibility of patients receiving medications or substances known to affect, or with the potential to affect the activity or pharmacokinetics of lapatinib will be determined following review of their use by the principal investigator 11. The effect of lapatinib on the developing human foetus at the recommended therapeutic dose is unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study she should inform her treating physician immediately. 12. Ability to understand and willingness to sign a written informed consent document 13. Able to swallow and retain oral medication
Key exclusion criteria	1. Patients who have had any chemotherapy, radiotherapy or endocrine therapy 2. Patients who have had prior treatment with EGFR-targeting therapies 3. Patients may not be receiving any other investigational concurrent anticancer therapy. In addition, all herbal (alternative) medicines are excluded. 4. Patients with metastatic disease 5. Patients with c-erbB2+++ (or c-erb++ provided confirmed by fluorescence in situ hybridization test [FISH]) 6. Patients not willing, or for whom it is planned, to resect the primary breast cancer 4-6 weeks after the start of the study 7. Patients with rapidly progressive disease, or local disease that, in the opinion of the investigator, is not amenable to surgical resection 8. Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis, and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events 9. History of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib 10. Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness or social situations that would limit compliance with study requirements 11. Pregnant women are excluded from this study because lapatinib is member of the 4-anilinoquinazoline class of kinase inhibitors with the potential for teratogenic or abortifacient effects. There is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with lapatinib; breastfeeding should be discontinued if the mother is treated with lapatinib 12. Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with lapatinib. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated. 13. Patients with gastrointestinal (GI) tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g. Crohn's or ulcerative colitis) 14. Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors 15. Any concomitant severe skin disorder 16. Hormone replacement therapy (HRT) must have been discontinued at least 2 weeks prior to the start of trial medication 17. Clinical or ultrasound assessment of the breast mass may, therefore, have to be repeated prior to the start of trial medication in this case, and only patients who show no evidence of any degree of regression following discontinuation of the HRT will be entered on the study
Date of first enrolment	01/09/2006
Date of final enrolment	31/08/2008

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

8th Floor Cycotron Building

London
W12 0NN
United Kingdom

Sponsor information

Imperial College London (UK)
University/education

Clinical Research Office
G02
Sir Alexander Fleming Building
South Kensington
London
SW7 2A2
United Kingdom

Website	http://www.imperial.ac.uk
"ROR"	https://ror.org/041kmwe10

Funders

Funder type

Industry

GlaxoSmithKline (UK)
Government organisation / For-profit companies (industry)

Alternative name(s): GlaxoSmithKline plc., GSK plc., GSK
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Plain English results				No	Yes
Results article	results	01/07/2012		Yes	No

Editorial Notes

26/10/2018: Cancer Research UK lay results summary link added to Results (plain English)