Entinostat, Lapatinib Ditosylate and Trastuzumab in Treating Patients With Locally Recurrent or Distant Relapsed Metastatic Breast Cancer Previously Treated With Trastuzumab Only
2019年5月17日 更新者：National Cancer Institute (NCI)
Phase I and Phase I Trastuzumab Cohort Study of Entinostat, Lapatinib and Trastuzumab in Patients With HER2-Positive Metastatic Breast Cancer in Whom Trastuzumab Has Failed
This phase I trial studies the side effects and best dose of entinostat when given together with lapatinib ditosylate and trastuzumab in treating patients with breast cancer that has spread from the original (primary) tumor to distant organs or distant lymph nodes or has recurred (come back) at or near the same place as the original (primary) tumor, usually after a period of time during which the cancer could not be detected.
Entinostat and lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Monoclonal antibodies, such as trastuzumab, may interfere with the ability of tumor cells to grow and spread.
Giving entinostat together with lapatinib ditosylate and trastuzumab may kill more tumor cells.
調査の概要
状態
完了
詳細な説明
PRIMARY OBJECTIVES:
I. To determine the recommended phase II dose (RP2D) for entinostat in combination with lapatinib (lapatinib ditosylate) in patients whom trastuzumab has failed for human epidermal growth factor receptor 2+ (HER2+) metastatic breast cancer (Phase I).
II. To determine the maximum tolerated dose (MTD) for entinostat in combination with lapatinib and trastuzumab in patients whom trastuzumab has failed for HER2+ metastatic breast cancer (Phase I Trastuzumab Cohort).
SECONDARY OBJECTIVES:
I. To determine the toxicity of combination therapy with entinostat and lapatinib in patients whom trastuzumab has failed for HER2+ metastatic breast cancer (Phase I).
II. To determine the toxicity of entinostat in combination with lapatinib and trastuzumab in patients whom trastuzumab has failed for HER2+ metastatic breast cancer (Phase I Trastuzumab Cohort).
EXPLORATORY OBJECTIVES:
I. Determine whether the 2-drug combination modulates the expression of HER2, phosphorylated HER2 (pHER), epidermal growth factor receptor (EGFR), phosphorylated EGFR (pEGFR), v-akt murine thymoma viral oncogene homolog 1 (Akt), and phosphorylated Akt (pAkt) in breast tumors and/or circulating tumor cells (CTCs).
OUTLINE: This is a dose-escalation study of entinostat.
Patients receive entinostat orally (PO) on days 1 and 15 and lapatinib tosylate PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients in the Phase I trastuzumab cohort also receive maintenance dose of trastuzumab intravenously (IV) over 30-90 minutes every 3 weeks.
After completion of study treatment, patients are followed up for 28 days or until toxicities are resolved.
研究の種類
介入
入学 (実際)
37
段階
- フェーズ 1
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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Texas
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Houston、Texas、アメリカ、77030
- M D Anderson Cancer Center
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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:
- Patients have histological confirmation of invasive breast carcinoma
- Patients have locally recurrent or distant relapsed metastatic disease
- Patients have positive HER2 expression by immunohistochemistry (IHC) (3+) or fluorescence in situ hybridization (FISH) testing (> 2.0 ratio)
- Patients are able to swallow and retain oral medication (i.e., no uncontrolled vomiting, inability to swallow, or diagnosis of chronic malabsorption)
- Patients have Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Patients must have received prior trastuzumab for > 2 month period before disease recurrence or recurrence or progression while on trastuzumab-based therapy
- Patients have ability and willingness to sign written informed consent
- Female patients of childbearing potential (a female not free from menses > 2 years or not surgically sterilized) must be willing to use an adequate barrier method of contraception to prevent pregnancy or agree to abstain from heterosexual activity throughout the study; male patients who are able to father children must use an adequate barrier method of contraception
- Female patients of childbearing potential must have negative serum pregnancy test within 14 days of starting protocol therapy
- Patients with brain metastasis have no signs of progressive disease 4 months after the completion of brain metastasis treatment (radiation therapy, surgery, etc.) do not require anticonvulsants or corticosteroids, and have been off such drugs for at least 7 days
- Both men and women and members of all races and ethnic groups are eligible for this trial
Exclusion Criteria:
- Patients are receiving concurrent anti-cancer therapy (chemotherapy, immunotherapy, biological therapy and hormonal therapy) while taking study medication
- Serum bilirubin >= 1.5 x upper limit of normal (ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >= 3 x ULN (with or without liver metastasis [mets])
- Absolute neutrophil count (ANC) < 1.5
- Hemoglobin =< 9
- Platelet =< 140,000
- Patients have an active infection and require intravenous (IV) or oral antibiotics
- Cardiac arrhythmia requiring maintenance medication
- History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug
- Patients have a concurrent disease or condition that would make them inappropriate for study participation, or any serious medical disorder that would interfere with patients' safety
- Serum creatinine > 2.0 mg/dL
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：なし
- 介入モデル：単一グループの割り当て
- 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：Treatment (entinostat, lapatinib ditosylate and trastuzumab)
Patients receive entinostat PO on days 1 and 15 and lapatinib tosylate PO on days 1-28.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients in the Phase I Trastuzumab Cohort also receive maintenance dose of trastuzumab IV over 30-90 minutes every 3 weeks.
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相関研究
与えられた IV
他の名前：
与えられたPO
他の名前：
与えられたPO
他の名前：
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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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RP2D for entinostat in combination with lapatinib ditosylate defined as the highest dose level in which 6 patients have been treated with at most 1 patient experiencing dose limiting toxicity
時間枠：Up to 28 days
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Up to 28 days
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二次結果の測定
結果測定 |
時間枠 |
|---|---|
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Incidence of grade III or IV toxicities, graded according to Common Terminology Criteria for Adverse Events version 4
時間枠：Up to 28 days
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Up to 28 days
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Changes in CTCs levels before and after the combination treatment of entinostat, lapatinib ditosylate and trastuzumab
時間枠：Baseline up to 28 days after completion of study treatment
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Summary statistics (mean, standard deviation, median, quartiles) will be summarized for these changes in CTCs and biomarkers by patient tumor response status (yes vs. no).
Changes will be compared between the two groups of patients (yes vs. no tumor response) using the two-sample t-test.
If the data is skewed, Wilcoxon rank-sum test will be used.
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Baseline up to 28 days after completion of study treatment
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Changes in phosphorylated Akt levels before and after the combination treatment of entinostat, lapatinib ditosylate and trastuzumab.
時間枠：Baseline up to 28 days after completion of study treatment
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Summary statistics (mean, standard deviation, median, quartiles) will be summarized for these changes in CTCs and biomarkers by patient tumor response status (yes vs. no).
Changes will be compared between the two groups of patients (yes vs. no tumor response) using the two-sample t-test.
If the data is skewed, Wilcoxon rank-sum test will be used.
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Baseline up to 28 days after completion of study treatment
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Changes in phosphorylated HER2 levels before and after the combination treatment of entinostat, lapatinib ditosylate and trastuzumab
時間枠：Baseline up to 28 days after completion of study treatment
|
Summary statistics (mean, standard deviation, median, quartiles) will be summarized for these changes biomarkers by patient tumor response status (yes vs. no).
Changes will be compared between the two groups of patients (yes vs. no tumor response) using the two-sample t-test.
If the data is skewed, Wilcoxon rank-sum test will be used.
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Baseline up to 28 days after completion of study treatment
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Changes in phosphorylated EGFR levels before and after the combination treatment of entinostat, lapatinib ditosylate and trastuzumab
時間枠：Baseline up to 28 days after completion of study treatment
|
Summary statistics (mean, standard deviation, median, quartiles) will be summarized for these changes biomarkers by patient tumor response status (yes vs. no).
Changes will be compared between the two groups of patients (yes vs. no tumor response) using the two-sample t-test.
If the data is skewed, Wilcoxon rank-sum test will be used.
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Baseline up to 28 days after completion of study treatment
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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。
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 (実際)
2012年1月10日
一次修了 (実際)
2016年2月16日
研究の完了 (実際)
2016年2月16日
試験登録日
最初に提出
2011年9月13日
QC基準を満たした最初の提出物
2011年9月13日
最初の投稿 (見積もり)
2011年9月14日
学習記録の更新
投稿された最後の更新 (実際)
2019年5月20日
QC基準を満たした最後の更新が送信されました
2019年5月17日
最終確認日
2019年5月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- NCI-2011-03222 (レジストリ識別子：CTRP (Clinical Trial Reporting Program))
- P30CA016672 (米国 NIH グラント/契約)
- UM1CA186688 (米国 NIH グラント/契約)
- U01CA062461 (米国 NIH グラント/契約)
- 8871 (その他の識別子：CTEP)
- NCI 8871
- 2010-0842 (その他の識別子：M D Anderson Cancer Center)
- CDR0000710891
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