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Study Of Lapatinib In Combination With Paclitaxel In The Treatment Of Newly Diagnosed Inflammatory Breast Cancer

Primary Purpose

Neoplasms, Breast

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Lapatinib
Paclitaxel
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neoplasms, Breast focused on measuring breast cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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). 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.

Sites / Locations

  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Overall study

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
May 25, 2005
Last Updated
May 27, 2017
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT00111787
Brief Title
Study Of Lapatinib In Combination With Paclitaxel In The Treatment Of Newly Diagnosed Inflammatory Breast Cancer
Official 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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
April 11, 2005 (Actual)
Primary Completion Date
November 1, 2006 (Actual)
Study Completion Date
November 1, 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasms, Breast
Keywords
breast cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Overall study
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Lapatinib
Intervention Description
Daily-monotherapy [1500 milligrams (mg)] for 14 days, then daily combination therapy (with weekly paclitaxel) for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Lapatinib
Intervention Description
Weekly (80mg/m^2) combination therapy (with daily Lapatinib) for 12 weeks
Primary Outcome Measure Information:
Title
Percentage of participants with pathologic complete response rate (pCR)
Description
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.
Time Frame
Week 12
Secondary Outcome Measure Information:
Title
Percentage of participants with pCR that underwent surgical resection
Description
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.
Time Frame
Week 12
Title
Percentage of participants with objective response rate (ORR) at the end of study (Response evaluation criteria in solid tumor [RECIST])
Description
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.
Time Frame
Week 14
Title
Percentage of participants with ORR at the end of study (Clinically Evaluable Skin Disease Criteria)
Description
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.
Time Frame
Week 14
Title
Percentage of participants with ORR at the end of study ('Best' of RECIST and Clinically Evaluable Skin Disease Criteria)
Description
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.
Time Frame
Week 14
Title
Percentage of participants with investigator-Assessed Best Response at the end of monotherapy phase (Day 14) (Clinically Evaluable Skin Disease Criteria)
Description
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.
Time Frame
Day 14
Title
Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Description
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.
Time Frame
Up to Week 14, surgical resection and post treatment
Title
Number of participants with shift from Baseline in hematological toxicity grade
Description
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.
Time Frame
Day 14 and up to Week 23, surg resection and post treatment
Title
Number of participants with shift from Baseline in clinical chemistry toxicity grade
Description
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.
Time Frame
Day 14, Week 4, 8, 12, 16, 20, Surg resection and post treatment
Title
Change from Baseline in vital signs- Systolic blood pressure (SBP) and Diastolic blood pressure (DBP)
Description
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.
Time Frame
Day 14, Week 1 and up to Week 24, surg resection and post treatment
Title
Change from Baseline in vital signs- Heart Rate (HR)
Description
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.
Time Frame
Day 14, Week 1 and up to Week 24, surg resection and post treatment
Title
Change from Baseline in vital signs- Body temperature
Description
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.
Time Frame
Day 14, Week 1 and up to Week 24, surg resection and post treatment
Title
Number of participants with abnormal electrocardiogram (ECG) findings
Description
ECG was performed at screening and at unscheduled visits. Participants with abnormal clinically significant and abnormal not clinically significant ECG findings was reported.
Time Frame
Screening and unscheduled
Title
Number of participants with change from Baseline in echocardiogram (ECHO) or Multi-gated angiogram (MUGA) results at any post Baseline visit
Description
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.
Time Frame
Screening, Week 8, 16, 24, post treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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). 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
GSK Investigational Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
GSK Investigational Site
City
Zion
State/Province
Illinois
ZIP/Postal Code
60099
Country
United States
Facility Name
GSK Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
GSK Investigational Site
City
Campbelltown
State/Province
New South Wales
ZIP/Postal Code
2560
Country
Australia
Facility Name
GSK Investigational Site
City
Liverpool
State/Province
New South Wales
ZIP/Postal Code
2170
Country
Australia
Facility Name
GSK Investigational Site
City
Randwick
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Facility Name
GSK Investigational Site
City
South Brisbane
State/Province
Queensland
ZIP/Postal Code
4101
Country
Australia
Facility Name
GSK Investigational Site
City
Bedford Park
State/Province
South Australia
ZIP/Postal Code
5042
Country
Australia
Facility Name
GSK Investigational Site
City
Box Hill
State/Province
Victoria
ZIP/Postal Code
3128
Country
Australia
Facility Name
GSK Investigational Site
City
Ringwood East
State/Province
Victoria
ZIP/Postal Code
3128
Country
Australia
Facility Name
GSK Investigational Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
GSK Investigational Site
City
Bayonne
ZIP/Postal Code
64100
Country
France
Facility Name
GSK Investigational Site
City
Lille Cedex
ZIP/Postal Code
59020
Country
France
Facility Name
GSK Investigational Site
City
Paris cedex 13
ZIP/Postal Code
75651
Country
France
Facility Name
GSK Investigational Site
City
Ramat Gan
ZIP/Postal Code
52621
Country
Israel
Facility Name
GSK Investigational Site
City
Auckland
Country
New Zealand
Facility Name
GSK Investigational Site
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
GSK Investigational Site
City
Girona
ZIP/Postal Code
17007
Country
Spain
Facility Name
GSK Investigational Site
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
GSK Investigational Site
City
Sfax
ZIP/Postal Code
3000
Country
Tunisia
Facility Name
GSK Investigational Site
City
Sfax
ZIP/Postal Code
3029
Country
Tunisia
Facility Name
GSK Investigational Site
City
Tunis
ZIP/Postal Code
1004
Country
Tunisia
Facility Name
GSK Investigational Site
City
Tunis
ZIP/Postal Code
1007
Country
Tunisia
Facility Name
GSK Investigational Site
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
20530274
Citation
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.
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Study Of Lapatinib In Combination With Paclitaxel In The Treatment Of Newly Diagnosed Inflammatory Breast Cancer

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