Study Of Lapatinib In Patients With Relapsed Or Refractory Inflammatory Breast Cancer
Information source: GlaxoSmithKline
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Neoplasms, Breast
Intervention: lapatinib (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: GlaxoSmithKline Official(s) and/or principal investigator(s): GSK Clinical Trials, Study Director, Affiliation: GlaxoSmithKline
Summary
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.
Clinical Details
Official title: A Phase II Study to Evaluate the Efficacy, Safety and Pharmacodynamics of Lapatinib in Patients With Relapsed or Refractory Inflammatory Breast Cancer
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Objective Response rate (complete response plus partial response)
Secondary outcome: Clinical benefit (progression free survival, time to progression, response duration)Assessment of clinical benefit, defined as CR or PR for at least 4 weeks, or SD for at least 6 months Calculation of progression-free survival, defined as the time between the first dose of investigational product and the first documented sign of disease progression or death. Calculation of time-to-response, defined as the time between the first dose of investigational product and the first documented CR or PR. Calculation of duration of response, defined as the time from initial documented CR or PR to the first documented sign of disease progression. Evaluation of changes in QoL and pain scale measurements collected on Day 1 and every 4 weeks while receiving study treatment. Evaluation of adverse events (AEs), changes in laboratory values and echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) results from pre-dose, during dosing and post-dose assessments Comparison of the effects of lapatinib on biomarkers that are involved in regulating tumor cell proliferation and survival (e.g., phosphorylated forms of Erk1/2 and Akt, STAT3, S6 Kinase, Bad, truncated ErbB2 and potentially other downstream mediators of tumor cell growth and survival) by quantitative IHC and by direct and genome-wide methods (e.g., direct sequencing and DNA microarray) in tumor tissue collected prior to and following 28 days of lapatinib monotherapy. Examination of the effects of lapatinib therapy on the levels of circulating ErbB1 and ErbB2 ECD and the proteomic profile of peripheral blood. Investigation of the use of FDG-PET to predict early response to treatment with lapatinib.
Detailed description:
This Phase II open label, multicenter study is designed to evaluate the efficacy, safety,
and pharmacodynamic effects of oral lapatinib administered as a single agent therapy to
patients with relapsed or refractory inflammatory breast cancer. Eligible patients must
have a diagnosis of inflammatory breast cancer based on clinicopathologic criteria, tumor
that is readily accessible for biopsy, and must have previously received treatment with an
anthracycline and taxane-containing regimen (30 patients) plus trastuzumab (90 patients).
Patients enrolled must have tumors that overexpress ErbB2, with or without co-expression of
ErbB1. The primary objective for this study is to evaluate the objective response rate
(defined as complete response plus partial response). Secondary objectives are to evaluate
clinical benefit including quality of life parameters, progression-free survival, overall
survival, time-to-response, response duration, safety and tolerability, pharmacodynamic
effects on intracellular mediators that regulate tumor cell growth and survival, as well as
effects on proteomic profile, and circulating levels of extracellular domains of ErbB1 and
ErbB2 in peripheral blood.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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:
1. Non-childbearing potential (i. e., women with functioning ovaries who have a current
documented tubal ligation or hysterectomy, or women who are postmenopausal); or
2. 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.
Locations and Contacts
GSK Investigational Site, Brussel 1000, Belgium
GSK Investigational Site, Bayonne 64100, France
GSK Investigational Site, Lyon Cedex 08 69373, France
GSK Investigational Site, Marseille Cedex 09 13273, France
GSK Investigational Site, Paris Cedex 20 75970, France
GSK Investigational Site, Paris Cedex 5 75248, France
GSK Investigational Site, Saint-Herblain 44805, France
GSK Investigational Site, Ramat Gan 52621, Israel
GSK Investigational Site, Zrifin 70300, Israel
GSK Investigational Site, Barcelona 08035, Spain
GSK Investigational Site, Barcelona 08036, Spain
GSK Investigational Site, Girona 17007, Spain
GSK Investigational Site, Madrid 28041, Spain
GSK Investigational Site, Sfax 3029, Tunisia
GSK Investigational Site, Sfax 3000, Tunisia
GSK Investigational Site, Tunis 1004, Tunisia
GSK Investigational Site, Tunis 1007, Tunisia
GSK Investigational Site, London SW3 6JJ, United Kingdom
GSK Investigational Site, Miami, Florida 33136-1002, United States
GSK Investigational Site, Chicago, Illinois 60637, United States
GSK Investigational Site, Zion, Illinois 60099, United States
GSK Investigational Site, Bethesda, Maryland 20892-1201, United States
GSK Investigational Site, Detroit, Michigan 48201, United States
GSK Investigational Site, St. Louis, Missouri 63110, United States
GSK Investigational Site, Durham, North Carolina 27710, United States
GSK Investigational Site, Toronto, Ontario M4N 3M5, Canada
GSK Investigational Site, Seattle, Washington 98109, United States
Additional Information
Starting date: March 2005
Last updated: May 4, 2015
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