Last updated: 11/04/2018 06:24:45
Study Of Lapatinib In Patients With Relapsed Or Refractory Inflammatory Breast Cancer
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A Phase II Study to Evaluate the Efficacy, Safety and Pharmacodynamics of Lapatinib in Patients with Relapsed or Refractory Inflammatory Breast Cancer
Trial description: This study was designed to determine how effective and safe a new investigational drug, lapatinib, is in treating patients with treatment refractory or relapsed inflammatory breast cancer. Tumor tissue collected pre-treatment and at Day 28 will be examined for biologic activity by IHC (immunohistochemistry). Treatment will consist of daily oral therapy with lapatinib. A patient may continue treatment as long as they are receiving benefit. Blood samples for hematology and chemistry panels, MUGA/ECHO (multigated acquisition/echocardiogram) exams and physical exams will be performed throughout the study to monitor safety.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:
Number of participants with investigator-assessed best complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) as per RECIST and Clincally Evaluable Skin Disease Criteria.
Timeframe: Up to Day 84
Best Objective Overall Response Rate (ORR)
Timeframe: Up to Day 84
Secondary outcomes:
Progression free rate at Week 24 as per RECIST criteria
Timeframe: Up to 24 weeks
Time to progression-free survival
Timeframe: Up to 24 weeks
Time to overall survival
Timeframe: Up to 24 weeks
Number of participants with response at Week 4, 8, 12 and 16
Timeframe: Week 4, 8, 12 and 16
Duration of Response
Timeframe: Up to Day 84
Changes from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 (EORTC-QLQ-C30) Domain Scores
Timeframe: Baseline (Day 1) up to Week 52
Changes in Brief Pain Inventory-Short Form (BPI-SF) Scores Relative to Baseline
Timeframe: Baseline (Day 1) and Week 48
Number of participants with any adverse events
Timeframe: Up to 274 weeks
Number of Participants With Shifts From Baseline to Grade 3 or 4 in Hematology Values
Timeframe: Up to 72 weeks
Number of Participants With Shifts From Baseline to Grade 3 or 4 in Clinical Chemistry Values
Timeframe: Up to 72 weeks
Number of participants with any increase, 0- <20 decrease, >=20 decrease, and >=20 decrease + below lower limit of normal from baseline in Left Ventricular Ejection Fraction Results on the basis of echocardiogram
Timeframe: Up to Week 65
Interventions:
Drug: lapatinib
Enrollment:
153
Observational study model:
Not applicable
Primary completion date:
2007-17-09
Time perspective:
Not applicable
Clinical publications:
Kaufman B, Trudeau M, Awada A, Blackwell K, Bachelot T, Salazar V, DeSilvio M, Westlund R, Zaks T, Spector N, Johnston S.Lapatinib monotherapy in patients with HER2-overexpressing relapsed or refractory infl ammatory breast cancer: fi nal results and survival of the expanded HER2+ cohort in EGF103009, a phase II study.Lancet Oncol.2009;10(6):581-588
Kaufman B, Wu Y, Amonkar M, Sherrill B, Bachelot T, Salazar V, Viens P, Johnston S. Impact of Lapatinib Monotherapy on Quality of Life and Pain Symptoms in Patients With HER2+ Relapsed or Refractory Inflammatory Breast Cancer. [Curr Med Res Opin]. 2010;26(5):1065-1073.
Kaufman B, Trudeau M, Awada A, Blackwell K, Bachelot T, Salazar V, DeSilvio M, Westlund R, Zaks T, Spector N, Johnston S. Lapatinib monotherapy in patients with HER2-overexpressing relapsed or refractory infl ammatory breast cancer: fi nal results and survival of the expanded HER2+ cohort in EGF103009, a phase II study. Lancet Oncol. 2009;10(6):581-588.
Kaufman B, Wu Y, Amonkar M, Sherrill B, Bachelot T, Salazar V, Viens P, Johnston S. Impact of Lapatinib Monotherapy on Quality of Life and Pain Symptoms in Patients With HER2+ Relapsed or Refractory Inflammatory Breast Cancer. Curr Med Res Opin. 2010;26(5):1065-1073.
Medical condition
Neoplasms, Breast
Product
lapatinib
Collaborators
Not applicable
Study date(s)
March 2005 to May 2010
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- Must have a life expectancy of at least 12 weeks.
- Has a left ventricular ejection fraction (LVEF) ≥ 50%, or ≥ lower limit of normal for the institution, based on ECHO or MUGA.
- Is clinically assessed to have inadequate venous access for protocol-related blood draws.
- Has a clinically significant electrocardiogram (ECG) abnormality.
Inclusion and exclusion criteria
Inclusion criteria:
- Must have a life expectancy of at least 12 weeks.
- Has a left ventricular ejection fraction (LVEF) ≥ 50%, or ≥ lower limit of normal for the institution, based on ECHO or MUGA.
- Aspartate and alanine transaminase (AST or ALT) ≤ 3 times the upper limit of the reference range (patients with liver metastases may have AST and ALT ≤ 5 times the upper limit of the reference range and may be enrolled).
- Total bilirubin ≤ 3.0 mg/dL.
- Serum creatinine ≤ 2.0 mg/dL or calculated creatinine clearance (CrCl) ≥ 30 mL/min
- Adequate bone marrow function. Hemoglobin ≥ 9 gm/dL. Absolute granulocyte count ≥ 1,500/mm³ (1.5 x 10^9/L). Platelets ≥ 75,000/mm³ (100 x 10^9/L).
- Recovered or stabilized sufficiently from side effects associated with previous chemotherapy, surgery or radiotherapy.
- Provided written informed consent.
- ECOG (Eastern Cooperative Oncology Group) performance status 0 to 2.
- Able to swallow and retain oral medication.
- Male or female, if female: A female is eligible to enter and participate in the study if she is of: a. Non-childbearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation or hysterectomy, or women who are postmenopausal); or b. Childbearing potential (i.e., women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility. This category includes women with oligomenorrhoea (severe), women who are perimenopausal, and young women who have begun to menstruate), has a negative serum pregnancy test at screening, and agrees to one of the following where considered acceptable to the local IRB/IEC: Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm). Abstinence from sexual intercourse from 2 weeks prior to administration of the investigational product, throughout the active study treatment period, and through the post-treatment follow-up visit (to occur 28 days after last dose of investigational product). Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject. Implants of levonorgestrel. Injectable progestogen. Any intrauterine device (IUD) with a documented failure rate of less than 1% per year. Oral contraceptives (either combined or progestogen only). Barrier methods including diaphragm or condom with a spermicide.
- At least 18 years of age.
- Has either measurable disease by Response Evaluation Criteria in Solid Tumors (RESIST) or clinically evaluable skin disease. Measurable lesions may be in the field of prior adjuvant irradiation; however, there must be at least an 8 week period between the last radiation treatment and the baseline scan documenting disease status for the lesion to be measurable.
- Tumor that is accessible for biopsy.
- Tumor that overexpresses ErbB2 defined as 3+ by IHC or FISH +. The ErbB 2 overexpression must be documented prior to dosing.
- Documented disease progression or relapse following treatment, which must have contained a taxane and anthracycline-containing regimen in the adjuvant or metastatic setting (30 patients) plus trastuzumab (90 patients)
- Histological diagnosis of breast carcinoma with a clinical diagnosis of IBC based on the presence of inflammatory changes in the involved breast, including diffuse erythema and edema (peau d'orange), with or without an underlying palpable mass involving the majority of the skin of the breast. Pathologic evidence of dermal lymphatic invasion should be noted but is not required for diagnosis.
Exclusion criteria:
- Is clinically assessed to have inadequate venous access for protocol-related blood draws.
- Has a clinically significant electrocardiogram (ECG) abnormality.
- Has Class II to IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
- Has physiological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
- Is currently receiving oral steroid treatment (inhaled steroids are permitted), or any other medication on the prohibited medications list
- Is currently receiving amiodarone or has received amiodarone in the 6 months prior to screening.
- Has received chemotherapy, immunotherapy, biologic therapy or hormonal therapy within the past 14 days, with the exception of mitomycin C within the past 6 weeks.
- Has received treatment with any investigational drug in the previous 4 weeks.
- Has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the investigational product. These include other anilinoquinazolines, such as gefitinib [Iressa], erlotinib [Tarceva], or other chemically related compounds.
- Is considered medically unfit for the study by the investigator as a result of the medical interview, physical exam, or screening investigations.
- Has evidence of symptomatic or uncontrolled brain metastases or leptomeningeal disease. Patients with brain metastases treated by surgery and/or radiotherapy are eligible if neurologically stable and do not require steroids or anticonvulsants.
- Has malabsorption syndrome, a disease affecting gastrointestinal function, or resection of the stomach or small bowel.
- Is a pregnant or lactating female.
Trial location(s)
Location
GSK Investigational Site
Chicago, Illinois, United States, 60637
Status
Study Complete
Location
GSK Investigational Site
Detroit, Michigan, United States, 48201
Status
Study Complete
Location
GSK Investigational Site
Bethesda, Maryland, United States, 20892-1201
Status
Study Complete
Location
GSK Investigational Site
Durham, North Carolina, United States, 27710
Status
Study Complete
Location
GSK Investigational Site
St. Louis, Missouri, United States, 63110
Status
Study Complete
Location
GSK Investigational Site
Seattle, Washington, United States, 98109
Status
Study Complete
Location
GSK Investigational Site
Miami, Florida, United States, 33136-1002
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2007-17-09
Actual study completion date
2010-31-05
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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