Exploratory Lapatinib (Positron Emission Tomography) PET Study in Subjects With Breast Cancer - Full Text View

Sponsor:	GlaxoSmithKline
Information provided by (Responsible Party):	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT01290354

Purpose

The purpose of this study is to find out how much lapatinib can enter both normal brains and brains in which tumours secondary to breast cancer have developed.

Condition	Intervention	Phase
Cancer	Drug: Lapatinib Drug: [11C] lapatinib	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Pharmacodynamics Study Intervention Model: Single Group Assignment Masking: Open Label
Official Title:	An Open-label Positron Emission Tomography Study to Investigate and Quantify Brain and Tumour Penetration of [11C]Lapatinib in Subjects With HER2-overexpressing Breast Cancer.

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Lapatinib Lapatinib Ditosylate

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Brain penetration of [11C]lapatinib [ Time Frame: 8 days ] [ Designated as safety issue: No ]
Brain tumour penetration of [11C]lapatinib [ Time Frame: 8 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Safety as assessed by number of subjects with adverse events [ Time Frame: 16-19 days ] [ Designated as safety issue: Yes ]
[11C]lapatinib uptake in non-brain tumour sites [ Time Frame: 8 days ] [ Designated as safety issue: No ]

Enrollment:	10
Study Start Date:	September 2011
Estimated Study Completion Date:	August 2012
Estimated Primary Completion Date:	August 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Lapatinib	Drug: Lapatinib Unlabelled, administered orally Other Names: Tykerb Tyverb Drug: [11C] lapatinib Radiolabelled, administered intravenously

Detailed Description:

Lapatinib is an anti-cancer drug taken by mouth which inhibits the HER2 protein, overexpressed in some breast tumours. It is not known whether lapatinib passes through the blood-brain barrier, and, therefore, whether it can target secondary tumours in the brain. This study will investigate whether lapatinib does indeed enter the brain.

Subjects with HER2-overexpressing breast cancer, with and without brain metastases, will receive lapatinib tablets daily for 8 days. The subjects will also receive lapatinib with a small amount of radioactivity attached on the first and last days of dosing to investigate whether it is taken up by the brain, using positron emission tomography (PET) scans.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Female, aged >/= 18 years old
Advanced or metastatic breast cancer with overexpression of HER2
Be able to provide written informed consent and comply with protocol requirements
If of child-bearing potential, using adequate and medically acceptable contraception method
Have an ECOG performance status of 0-2 and be in stable condition
Able to lie still on the PET scanner for approx. 1.5-2 h
Adequate hepatic and renal function
Patent ulnar artery or collateral arterial blood vessels
If have CNS metastases, disease must be stable
Subjects with CNS metastases should have at least a single 1 cm diameter lesion as shown on contrast MRI

Exclusion Criteria:

Subjects with brain metastases who have undergone prior CNS surgery
Significant brain abnormalities, neurological disorder, psychiatric disorder or previous brain damage
Diabetes type I
History of HIV, hepatitis B or hepatitis C infection
Current alcohol and/or drug abuse
Positive pregnancy test or lactation
Malabsorption syndrome or disease affecting gastrointestinal function that may affect intestinal absorption
Requirement for additional concurrent anti-cancer therapy
History of uncontrolled or symptomatic angina
Concurrent treatment with an investigational agent or anti-cytotoxic therapy or use within 30 days or 5 half-lives
Known hypersensitivity reaction of idiosyncrasy to drugs chemically related to lapatinib or its excipients
Concurrent treatment with CYP3A4 inducers and inhibitors
Unwillingness to refrain from consuming red wine, Seville oranges, grapefruit, pomelo, grapefruit hybrids and their juices from 7 days before Day 1 until collection of the final pharmacokinetic sample
Known history of claustrophobia
Known contraindications or likely risk of toxicity to gadlinium-based MRI contrast media
Presence of cardiac pacemaker, other electronic device or ferromagnetic metal foreign bodies
Any abnormality found on the MRI scan which, in the opinion of the investigator, may influence the outcome of the PET scans or affect the safety of the volunteer
Acute or active hepatic or biliary disease
Any medical condition or circumstance making the volunteer unsuitable for participation in the study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01290354

Locations

United Kingdom
GSK Investigational Site
London, United Kingdom, W6 8RF
GSK Investigational Site
London, United Kingdom, W12 0NN

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT01290354 History of Changes
Other Study ID Numbers:	112867
Study First Received:	January 27, 2011
Last Updated:	May 17, 2012
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:

Brain penetration
positron emission tomography
Lapatinib

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Lapatinib

Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 23, 2012