Study Of Lapatinib In Patients With Relapsed Or Refractory Inflammatory Breast Cancer
2015年9月24日 更新者：GlaxoSmithKline
A Phase II Study to Evaluate the Efficacy, Safety and Pharmacodynamics of Lapatinib in Patients With Relapsed or Refractory Inflammatory Breast Cancer
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.
調査の概要
詳細な説明
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.
研究の種類
介入
入学 (実際)
126
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Florida
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Miami、Florida、アメリカ、33136-1002
- GSK Investigational Site
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Illinois
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Chicago、Illinois、アメリカ、60637
- GSK Investigational Site
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Zion、Illinois、アメリカ、60099
- GSK Investigational Site
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Maryland
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Bethesda、Maryland、アメリカ、20892-1201
- GSK Investigational Site
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Michigan
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Detroit、Michigan、アメリカ、48201
- GSK Investigational Site
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Missouri
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St. Louis、Missouri、アメリカ、63110
- GSK Investigational Site
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North Carolina
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Durham、North Carolina、アメリカ、27710
- GSK Investigational Site
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Washington
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Seattle、Washington、アメリカ、98109
- GSK Investigational Site
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London、イギリス、SW3 6JJ
- GSK Investigational Site
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Ramat Gan、イスラエル、52621
- GSK Investigational Site
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Zrifin、イスラエル、70300
- GSK Investigational Site
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Ontario
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Toronto、Ontario、カナダ、M4N 3M5
- GSK Investigational Site
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Barcelona、スペイン、08036
- GSK Investigational Site
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Barcelona、スペイン、08035
- GSK Investigational Site
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Girona、スペイン、17007
- GSK Investigational Site
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Madrid、スペイン、28041
- GSK Investigational Site
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Sfax、チュニジア、3000
- GSK Investigational Site
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Sfax、チュニジア、3029
- GSK Investigational Site
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Tunis、チュニジア、1007
- GSK Investigational Site
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Tunis、チュニジア、1004
- GSK Investigational Site
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Bayonne、フランス、64100
- GSK Investigational Site
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Lyon Cedex 08、フランス、69373
- GSK Investigational Site
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Marseille Cedex 09、フランス、13273
- GSK Investigational Site
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Paris Cedex 20、フランス、75970
- GSK Investigational Site
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Paris Cedex 5、フランス、75248
- GSK Investigational Site
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Saint-Herblain、フランス、44805
- GSK Investigational Site
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Bruxelles、ベルギー、1000
- GSK Investigational Site
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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:
- Non-childbearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation or hysterectomy, or women who are postmenopausal); or
- 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.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：非ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：Lapatinib
Single arm study of lapatinib with no comparator arm.
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Tyrosine kinase inhibitor administered daily at 1500 mg/kg
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
時間枠 |
|---|---|
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Objective Response rate (complete response plus partial response)
時間枠：Week 84
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Week 84
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二次結果の測定
結果測定 |
時間枠 |
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Clinical benefit (progression free survival, time to progression, response duration)
時間枠：week 84
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week 84
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Assessment of clinical benefit, defined as CR or PR for at least 4 weeks, or SD for at least 6 months
時間枠：week 84
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week 84
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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.
時間枠：week 84
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week 84
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Calculation of time-to-response, defined as the time between the first dose of investigational product and the first documented CR or PR.
時間枠：week 84
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week 84
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Calculation of duration of response, defined as the time from initial documented CR or PR to the first documented sign of disease progression.
時間枠：week 84
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week 84
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Evaluation of changes in QoL and pain scale measurements collected on Day 1 and every 4 weeks while receiving study treatment.
時間枠：week 84
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week 84
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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
時間枠：week 84
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week 84
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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
時間枠：Day 28
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Day 28
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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.
時間枠：Day 28
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Day 28
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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.
時間枠：Day 28
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Day 28
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- 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 inflammatory breast cancer: final results and survival of the expanded HER2+ cohort in EGF103009, a phase II study. Lancet Oncol. 2009 Jun;10(6):581-8. doi: 10.1016/S1470-2045(09)70087-7. Epub 2009 Apr 24.
- Kaufman B, Wu Y, Amonkar MM, Sherrill B, Bachelot T, Salazar V, Viens P, Johnston S. Impact of lapatinib monotherapy on QOL and pain symptoms in patients with HER2+ relapsed or refractory inflammatory breast cancer. Curr Med Res Opin. 2010 May;26(5):1065-73. doi: 10.1185/03007991003680323.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2005年3月1日
一次修了 (実際)
2007年9月1日
研究の完了 (実際)
2010年5月1日
試験登録日
最初に提出
2005年3月18日
QC基準を満たした最初の提出物
2005年3月18日
最初の投稿 (見積もり)
2005年3月21日
学習記録の更新
投稿された最後の更新 (見積もり)
2015年9月28日
QC基準を満たした最後の更新が送信されました
2015年9月24日
最終確認日
2015年5月1日
詳しくは
本研究に関する用語
キーワード
その他の研究ID番号
- EGF103009
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
新生物、乳房の臨床試験
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Tianjin Medical University Cancer Institute and...Guangxi Medical University; Sun Yat-sen University; Chinese PLA General Hospital; The First Affiliated... と他の協力者完了