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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00111787




Registration number
NCT00111787
Ethics application status
Date submitted
25/05/2005
Date registered
25/05/2005
Date last updated
27/05/2017

Titles & IDs
Public title
Study Of Lapatinib In Combination With Paclitaxel In The Treatment Of Newly Diagnosed Inflammatory Breast Cancer
Scientific title
A Phase II Study to Evaluate the Efficacy, Safety, and Pharmacodynamics of Lapatinib in Combination With Paclitaxel as Neoadjuvant Therapy in Patients With Newly Diagnosed Inflammatory Breast Cancer
Secondary ID [1] 0 0
EGF102580
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms, Breast 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lapatinib
Treatment: Drugs - Paclitaxel

Experimental: Overall study - A Single arm study with 2 cohorts of participants. Cohort A consists of participants with tumors overexpressing HER2 and/or EGFR. Cohort B consists of participants with tumors expressing EGFR without overexpressing HER2.


Treatment: Drugs: Lapatinib
Daily-monotherapy [1500 milligrams (mg)] for 14 days, then daily combination therapy (with weekly paclitaxel) for 12 weeks

Treatment: Drugs: Paclitaxel
Weekly (80mg/m^2) combination therapy (with daily Lapatinib) for 12 weeks

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of participants with pathologic complete response rate (pCR) - pCR was defined as the percentage of participants who achieved an assessment of complete response (CR) following pathologic review of resected tissue. CR was the disappearance of all target lesions. Participants in each cohort with unknown or missing response (i.e., those that did not undergo surgery) were included in the denominator when calculating the percentage. From an efficacy standpoint, the HER2+ population response was considered to be of special interest.
Timepoint [1] 0 0
Week 12
Secondary outcome [1] 0 0
Percentage of participants with pCR that underwent surgical resection - pCR for participants that underwent surgical (surg) resection was defined as the percentage of participants within each cohort who achieved an assessment of CR following pathologic review of resected tissue. CR was the disappearance of all target lesions. Participants in each cohort that did not undergo surgical resection were excluded from the denominator when calculating the percentage. From an efficacy standpoint, the HER2+ population response was considered to be of special interest.
Timepoint [1] 0 0
Week 12
Secondary outcome [2] 0 0
Percentage of participants with objective response rate (ORR) at the end of study (Response evaluation criteria in solid tumor [RECIST]) - ORR at the end of the study was defined as the number of participants within each cohort who had a confirmed CR or partial response (PR) at the end of the study divided by the total number of participants enrolled in each cohort. CR was the disappearance of all target lesions. PR was at least a 30 percent decrease in the sum of the longest diameter of target lesions, taking as a reference, the Baseline sum longest diameter. Each participant's response was based on the investigator assessment of best response using RECIST criteria. Participants in each cohort with unknown or missing response was treated as non-responders; i.e. they were included in the denominator when calculating the percentage. From an efficacy standpoint, the HER2+ population was considered to be of special interest.
Timepoint [2] 0 0
Week 14
Secondary outcome [3] 0 0
Percentage of participants with ORR at the end of study (Clinically Evaluable Skin Disease Criteria) - ORR at the end of the study was defined as the number of participants within each cohort who had a confirmed CR or PR at the end of the study divided by the total number of participants enrolled in each cohort. CR was the disappearance of all target lesions. PR was at least a 30 percent decrease in the sum of the longest diameter of target lesions, taking as a reference, the Baseline sum longest diameter. Each participant's response was based on the investigator assessment of best response using Clinically Evaluable Skin Disease Criteria. Participants in each cohort with unknown or missing response was treated as non-responders; i.e. they were included in the denominator when calculating the percentage. From an efficacy standpoint, HER2+ population was considered to be of special interest.
Timepoint [3] 0 0
Week 14
Secondary outcome [4] 0 0
Percentage of participants with ORR at the end of study ('Best' of RECIST and Clinically Evaluable Skin Disease Criteria) - ORR at the end of the study was defined as the number of participants within each cohort who had a confirmed CR or PR at the end of the study divided by the total number of participants enrolled in each cohort. CR was the disappearance of all target lesions. PR was at least a 30 percent decrease in the sum of the longest diameter of target lesions, taking as a reference, the Baseline sum longest diameter. The best response of the participant was defined by the 'Best' combined response (RECIST and Clinically Evaluable Skin Disease Criteria) provided there is no evidence of disease progression. Participants in each cohort with unknown or missing response was treated as non-responders; i.e. they were included in the denominator when calculating the percentage. From an efficacy standpoint, the HER2+ population was considered to be special interest.
Timepoint [4] 0 0
Week 14
Secondary outcome [5] 0 0
Percentage of participants with investigator-Assessed Best Response at the end of monotherapy phase (Day 14) (Clinically Evaluable Skin Disease Criteria) - ORR at the end of the monotherapy phase was defined as the percentage of participants within each cohort who had a confirmed CR or PR at the end of lapatinib monotherapy (Day 14) divided by the total number of participants enrolled in each cohort. CR was the disappearance of all target lesions. PR was at least a 30 percent decrease in the sum of the longest diameter of target lesions, taking as a reference, the Baseline sum longest diameter. Each participant's response was based on the investigator assessment of best response using clinically evaluable skin disease criteria. Participants in each cohort with unknown or missing response was treated as non-responders; i.e. they were included in the denominator when calculating the percentage. From an efficacy standpoint, the HER2+ population was considered to be special interest.
Timepoint [5] 0 0
Day 14
Secondary outcome [6] 0 0
Number of participants with adverse events (AEs) and serious adverse events (SAEs) - An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE was defined as any untoward medical occurrence that, at any dose that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect, resulted in deterioration in left ventricular cardiac function and caused Grade 3 or 4 interstitial pneumonitis.
Timepoint [6] 0 0
Up to Week 14, surgical resection and post treatment
Secondary outcome [7] 0 0
Number of participants with shift from Baseline in hematological toxicity grade - Hematology was summarized for hemoglobin (Hb), platelets, white blood cell count (WBC), neutrophils (Neu), lymphocytes by scheduled assessment and also according to the maximum common terminology criteria (CTC) toxicity grade. Baseline was the most recent lab value prior to and within two weeks of the first dose of lapatinib. Change from Baseline was calculated as the value at each visit minus Baseline value.
Timepoint [7] 0 0
Day 14 and up to Week 23, surg resection and post treatment
Secondary outcome [8] 0 0
Number of participants with shift from Baseline in clinical chemistry toxicity grade - Clinical chemistry was summarized for sodium, potassium (K), bicarbonate (bicarb), albumin (alb), calcium, gamma glutamyl transferase (GGT), creatinine (creat), total bilirubin (TB), alkaline phosphatase (ALP), aspartate amino transferase (AST) and alanine amino transferase (ALT) by scheduled assessment and also according to the maximum CTC toxicity grade. Baseline was the most recent lab value prior to and within two weeks of the first dose of lapatinib. Change from Baseline was calculated as the value at each visit minus Baseline value.
Timepoint [8] 0 0
Day 14, Week 4, 8, 12, 16, 20, Surg resection and post treatment
Secondary outcome [9] 0 0
Change from Baseline in vital signs- Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) - Vitals signs (SBP and DBP) were assessed from screening until the post treatment phase. Baseline was the most recent blood pressure (BP) mean prior to the first dose of lapatinib. Change from Baseline was calculated as the mean at each visit minus the mean at Baseline.
Timepoint [9] 0 0
Day 14, Week 1 and up to Week 24, surg resection and post treatment
Secondary outcome [10] 0 0
Change from Baseline in vital signs- Heart Rate (HR) - Vitals signs (HR) were assessed from screening until the post treatment phase. Baseline was the most recent BP mean prior to the first dose of lapatinib. Change from Baseline was calculated as the mean at each visit minus the mean at Baseline.
Timepoint [10] 0 0
Day 14, Week 1 and up to Week 24, surg resection and post treatment
Secondary outcome [11] 0 0
Change from Baseline in vital signs- Body temperature - Vitals signs (body temperature) were assessed from screening until the post treatment phase. Baseline was the most recent BP mean prior to the first dose of lapatinib. Change from Baseline was calculated as the mean at each visit minus the mean at Baseline.
Timepoint [11] 0 0
Day 14, Week 1 and up to Week 24, surg resection and post treatment
Secondary outcome [12] 0 0
Number of participants with abnormal electrocardiogram (ECG) findings - ECG was performed at screening and at unscheduled visits. Participants with abnormal clinically significant and abnormal not clinically significant ECG findings was reported.
Timepoint [12] 0 0
Screening and unscheduled
Secondary outcome [13] 0 0
Number of participants with change from Baseline in echocardiogram (ECHO) or Multi-gated angiogram (MUGA) results at any post Baseline visit - For ECHO and MUGA scans, the left ventricular ejection fraction (percent) was summarized for each scheduled assessment. Absolute change from Baseline was summarized according to the following categories: any increase, 0 to less than 20 percent decrease, >=20 percent decrease or >=20 percent decrease and below the lower limit of normal (LLN). Baseline was the most recent ECOG evaluation prior to the first dose of lapatinib. Change from Baseline was calculated as the value at the post treatment minus Baseline value.
Timepoint [13] 0 0
Screening, Week 8, 16, 24, post treatment

Eligibility
Key inclusion criteria
Inclusion criteria:

- Tumor accessible for multiple biopsies

- ECOG (Eastern Cooperative Oncology Group) performance status 0-2

- Adequate bone marrow

- Renal and hepatic function

- LVEF (left ventricular ejection fraction) greater than 0% based on ECHO
(echocardiogram) or MUGA (multigated acquisition).
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- Females who are pregnant or nursing.

- Any unstable, pre-existing major medical condition.

- Received an investigational drug within the past 4 weeks.

- Had major surgery in the past 2 weeks.

- Currently receiving amiodarone or has received amiodarone in the past 6 months.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Campbelltown
Recruitment hospital [2] 0 0
GSK Investigational Site - Liverpool
Recruitment hospital [3] 0 0
GSK Investigational Site - Randwick
Recruitment hospital [4] 0 0
GSK Investigational Site - South Brisbane
Recruitment hospital [5] 0 0
GSK Investigational Site - Bedford Park
Recruitment hospital [6] 0 0
GSK Investigational Site - Box Hill
Recruitment hospital [7] 0 0
GSK Investigational Site - Ringwood East
Recruitment postcode(s) [1] 0 0
2560 - Campbelltown
Recruitment postcode(s) [2] 0 0
2170 - Liverpool
Recruitment postcode(s) [3] 0 0
2031 - Randwick
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
5042 - Bedford Park
Recruitment postcode(s) [6] 0 0
3128 - Box Hill
Recruitment postcode(s) [7] 0 0
3128 - Ringwood East
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
Canada
State/province [4] 0 0
Ontario
Country [5] 0 0
France
State/province [5] 0 0
Bayonne
Country [6] 0 0
France
State/province [6] 0 0
Lille Cedex
Country [7] 0 0
France
State/province [7] 0 0
Paris cedex 13
Country [8] 0 0
Israel
State/province [8] 0 0
Ramat Gan
Country [9] 0 0
New Zealand
State/province [9] 0 0
Auckland
Country [10] 0 0
Spain
State/province [10] 0 0
Barcelona
Country [11] 0 0
Spain
State/province [11] 0 0
Girona
Country [12] 0 0
Spain
State/province [12] 0 0
Valencia
Country [13] 0 0
Tunisia
State/province [13] 0 0
Sfax
Country [14] 0 0
Tunisia
State/province [14] 0 0
Tunis
Country [15] 0 0
United Kingdom
State/province [15] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This Study was designed to determine how effective and safe a new investigational drug,
lapatinib, is in combination with paclitaxel in treating patients with newly diagnosed
inflammatory breast cancer. Tumor tissue collected pre-treatment, following 14 days of
treatment and at the time of surgical resection will be examined for pathologic response and
biologic activity by IHC (immunohistochemistry) within the tumor. Treatment will consist of
14 days of lapatinib monotherapy followed by 12 weeks of combination therapy with lapatinib
and paclitaxel. Blood samples for hematology and chemistry panels, MUGA/ECHO exams and
physical exams will be performed throughout the study to monitor safety.
Trial website
https://clinicaltrials.gov/show/NCT00111787
Trial related presentations / publications
Boussen H, Cristofanilli M, Zaks T, DeSilvio M, Salazar V, Spector N. Phase II study to evaluate the efficacy and safety of neoadjuvant lapatinib plus paclitaxel in patients with inflammatory breast cancer. J Clin Oncol. 2010 Jul 10;28(20):3248-55. doi: 10.1200/JCO.2009.21.8594. Epub 2010 Jun 7.
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Other publications