Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Nervous System Diseases

Breast Neoplasms

Neoplasm Metastasis

Brain Neoplasms

Breast Diseases

Skin Diseases

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Trastuzumab

Tyrosine Kinase Inhibitors

Lapatinib

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

750 mg lapatinib administered orally twice daily

lapatinib

Novartis Pharmaceuticals

Determine how safe and effective lapatinib is when used to treat patients with ErbB2 overexpressing breast cancer that has spread to the brain and is still progressing there even after radiation treatment using WBRT (whole brain radiotherapy) or SRS (stereotactic radiosurgery) to the brain. Lapatinib is an oral drug that will be taken every day. Tests for safety and efficacy will be performed every 4 weeks or 8 weeks (depending on the test) during the course of the study.

Lapatinib for Brain Metastases In ErbB2-Positive Breast Cancer

A Phase II Study of Lapatinib for Brain Metastases in Subjects With ErbB2-Positive Breast Cancer Following Trastuzumab-based Systemic Therapy and Cranial Radiotherapy

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Summary of CNS Objective Response (Lapatinib Monotherapy - MITT Population)

Response to lapatinib in patients with progressive brain metastases from ErbB2-overexpressing breast cancer.

The primary indicator of drug efficacy was CNS objective response rate. A CNS objective response was defined as either a Complete response (CR) or Partial response (PR), as assessed by volumetric analysis of brain Magnetic resonance imaging (MRI), provided there was no progression of systemic disease outside of the CNS, increasing steroid requirements, or worsening of Neurological signs and symptoms (NSS)

A CNS objective response rate was defined as a 50% volumetric reduction in sum of CNS target lesions, with no new or progressive CNS or non-CNS lesions, no increases in tumor-related steroid requirements and no worsening of neurological signs or symptoms

Summary of CNS Objective Response (the Complete Response + Partial Response)

Physician-reported NSS worksheet is derived from 13 AEs and measured by NCI CTCAE v3.0 grouped into 7 categories: level of consciousness, neurological symptoms, cranial nerves, language, strength, sensation, \& ataxia. Improvement of NSS required: Decrease by 1 or more grades from baseline of any tumor-related NSS, with confirmation at least 4 wks later, No development or worsening in any tumor-related NSS during interval, No radiographic evidence of CNS progression (assessed by volumetric MRI) or systemic (non-CNS) progression (assessed by RECIST) during interval, Stable or decreasing steroids during interval as defined by GSK equivalent doses of an alternative corticosteroid or a dose increase for non-tumor related reasons didn't constitute a steroid increase. Improvement in any non-tumor associated NSS didn't constitute improvement in NSS. Neurological exam, using Neurological Examination Worksheet was assessed at baseline \& each 4 wks. Categories below are not mutually exclusive.

Summary of Proportion of Subjects with a CNS Objective Response or Improvement in Baseline NSS

The duration of CNS objective response, defined as the time from first CNS

Objective response until tumor progression at any site or death due to any cause.

A CNS objective response was defined as either a Complete Response (CR) or Partial Response (PR), as assessed by volumetric analysis of magnetic resonance imaging (MRI), provided there was no progression of systemic disease outside of the CNS, increasing steroid requirements, or worsening of tumor-related neurological signs or symptoms.

The CNS disease control rate, defined as the percentage of subjects with CR, PR or stable disease at Week 24

Summary of Kaplan-Meier Estimates for Progression Free Survival at Any Site

Overall survival (OS) defined as the time from initiation of investigational product to death due to any cause.

baseline to time of disease progression or death

Summary of Overall All-cause mortality (Main Study and Extension)

All cause mortality (on-treatment deaths) was collected for as long as participants could be contacted from FPFV until LPLV up to a maximum of 12 years and 3 months

SAEs are presented from main and extension phase

Cohort A subjects had Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and one or two prior trastuzumab-containing regimens, in total, for treatment of breast cancer in adjuvant and/or metastatic settings

EGF105084/Cohort A

Cohort B subjects had ECOG performance status 2 and/or more than 2 prior trastuzumab-containing regimens for treatment of breast cancer in the adjuvant and/or metastatic settings

EGF105084/Cohort B

Overall - Main Study and Extension Phase - 750 mg lapatinib administered orally twice daily Cohort A subjects had Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and one or two prior trastuzumab-containing regimens, in total, for treatment of breast cancer in adjuvant and/or metastatic settings.

Cohorts A

750mg lapatinib administered orally twice daily. Cohort B subjects had ECOG performance status 2 and/or more than 2 prior trastuzumab-containing regimens for treatment of breast cancer in the adjuvant and/or metastatic settings.

Cohort B

Total

Age, Continuous

<18 years

18-64 years

65-84 years

>85 years

Age, Customized

Sex: Female, Male

African American/African

American Indian/Alaskan Native

Asian - Central/South

Asian - Japanese

Asian - South-East Asian

Asia - East

Native Hawaiian or other Pacific Islander

White - Arabic/North African

White - White/ Caucasian/European

Mixed race

Unknown

Race/Ethnicity, Customized

Intent-to-Treat (ITT) Population is defined as all subjects who received at least one dose of study medication.

Outcome Quantitative Toxicities Associated with Oral Lapatinib are in Adverse Events section. No analysis was performed for 2 outcomes: Relationship of PET Uptake, as Predictors of Response; and Relationship Between Genetic Variants in Select Genes

Study Director

Complete response (CR)

Partial response (PR)

Stable disease (SD)

Progressive disease (PD)

750mg lapatinib administered orally twice daily. Cohort A subjects had Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and one or two prior trastuzumab-containing regimens, in total, for treatment of breast cancer in adjuvant and/or metastatic settings

Cohort A

Modified ITT (MITT) Population is defined as all subjects who received at least four doses (750 mg lapatinib 2x daily for 2 days) of study medication and who had measurable brain metastases (greater than or equal to 1cm in diameter) at baseline assessment. MITT was the primary population for analysis of efficacy data in lapatinib monotherapy arm.

The Number of Participants With Central Nervous System (CNS) Best Overall Response

The Percentage of Participants With Central Nervous System (CNS) Objective Response Rate - Response Rate (CR + PR)

Subjects with NSS improvement

>=20% volumetric reduction of lesion

any volumetric reduction of lesion

volumetric increase or withdrew

Overall - Main Study and Extension Phase - 750 mg lapatinib administered orally twice daily

Cohorts A and B

MITT population

Analysis was performed on combined cohorts in order to have a sufficient sample size to analyze association of CNS Volumetric Change from Baseline and NSS Improvement

Spots Global Cancer Trial Database for lap016a

Every month we try and update this database with for lap016a cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for lap016a

Every month we try and update this database with for lap016a cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for lap016a cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.